Endocrinology and Metabolism

Original Articles

Thyroid
Association of the Preoperative Controlling Nutritional Status (CONUT) Score with Clinicopathological Characteristics in Patients with Papillary Thyroid Carcinoma: Doohwa Kim, Myungsoo Im, Soree Ryang, Mijin Kim, Yun Kyung Jeon, Sang Soo Kim, Bo Hyun Kim; Endocrinol Metab. 2024;39(6):856-863. Published online November 15, 2024; DOI: https://doi.org/10.3803/EnM.2024.2006

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Abstract PDF Supplementary Material PubReader ePub: Background
The Controlling Nutritional Status (CONUT) score is an immunonutritional test tool based on serum albumin, total cholesterol, and lymphocyte counts. It has been studied as a simple prognostic predictor for various carcinomas. This study aimed to investigate the association between preoperative CONUT scores and the clinicopathological characteristics in papillary thyroid carcinoma (PTC) patients.
Methods
This study included 2,403 PTC patients who underwent total thyroidectomy between 2012 and 2016 at a single tertiary medical center. The CONUT scores were calculated based on preoperative blood tests. The clinicopathological characteristics were retrospectively reviewed. The patients were categorized by the CONUT score (relatively low, 0–2; relatively high, 3–5).
Results
Among the 2,997 PTC patients who underwent total thyroidectomy at Pusan National University Hospital between 2012 and 2016, those without preoperative blood test were excluded (n=149). Finally 2,403 patients were analyzed after excluding 439 patients taking lipid-lowering drugs and six patients without available T stage data after surgery. Based on the CONUT score, the relatively high score group had a lower body mass index (23.7±3.3 kg/m² vs. 21.9±2.9 kg/m², P<0.001), more advanced T stage (T stage 3/4, 5.9% vs. 11.4%, P=0.045), and higher extrathyroidal extension (2.1% vs. 7.6%, P=0.005).
Conclusion
Patients included in this large, single-center study all had a preoperative CONUT score of 0–5, but this study demonstrated that higher preoperative CONUT scores were significantly associated with advanced T stage and extrathyroidal extension. The CONUT score, which can be easily used in clinical practice, is thought to be helpful in predicting the aggressiveness of PTC.

Adrenal gland
The Modified S-GRAS Scoring System for Prognosis in Korean with Adrenocortical Carcinoma: Sun Kyung Baek, Seung Hun Lee, Seung Shin Park, Chang Ho Ahn, Sung Hye Kong, Won Woong Kim, Yu-Mi Lee, Su Jin Kim, Dong Eun Song, Tae-Yon Sung, Kyu Eun Lee, Jung Hee Kim, Kyeong Cheon Jung, Jung-Min Koh; Endocrinol Metab. 2024;39(5):803-812. Published online September 25, 2024; DOI: https://doi.org/10.3803/EnM.2024.2086

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Adrenocortical carcinomas (ACCs) are rare tumors with aggressive but varied prognosis. Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score, based on clinical and pathological factors, was found to best stratify the prognosis of European ACC patients. This study assessed the prognostic performance of modified S-GRAS (mS-GRAS) scores including modified grade (mG) by integrating mitotic counts into the Ki67 index (original grade), in Korean ACC patients.
Methods
Patients who underwent surgery for ACC between January 1996 and December 2022 at three medical centers in Korea were retrospectively analyzed. mS-GRAS scores were calculated based on tumor stage, mG (Ki67 index or mitotic counts), resection status, age, and symptoms. Patients were divided into four groups (0–1, 2–3, 4–5, and 6–9 points) based on total mS-GRAS score. The associations of each variable and mS-GRAS score with recurrence and survival were evaluated using Cox regression analysis, Harrell’s concordance index (C-index), and the Kaplan–Meier method.
Results
Data on mS-GRAS components were available for 114 of the 153 patients who underwent surgery for ACC. These 114 patients had recurrence and death rates of 61.4% and 48.2%, respectively. mS-GRAS score was a significantly better predictor of recurrence (C-index=0.829) and death (C-index=0.747) than each component (P<0.05), except for resection status. mS-GRAS scores correlated with shorter progression-free survival (P=8.34E-24) and overall survival (P=2.72E-13).
Conclusion
mS-GRAS scores showed better prognostic performance than tumor stage and grade in Asian patients who underwent surgery for ACC.

Thyroid
Prognosis of Poorly Differentiated Thyroid Carcinoma: A Systematic Review and Meta-Analysis: Ji Young Kim, Jae Kyung Myung, Soyun Kim, Kyung Tae, Yun Young Choi, Soo Jin Lee; Endocrinol Metab. 2024;39(4):590-602. Published online June 27, 2024; DOI: https://doi.org/10.3803/EnM.2024.1927

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Background
Poorly differentiated thyroid carcinoma (PDTC) accounts for a small portion of thyroid carcinomas but contributes to a significant proportion of thyroid carcinoma-associated deaths. The clinicopathological prognostic factors and clinical outcomes of PDTC remain unclear. We aimed to evaluate the clinical outcomes of patients with PDTC after curative treatment.
Methods
A comprehensive search was performed up to September 2023. We included studies investigating treatment outcomes in patients with PDTC who underwent initial surgery. The 5-year disease-free survival (DFS) and overall survival (OS) were extracted. In this meta-analysis, the enrolled PDTC histological criteria included 3rd, 4th, and 5th World Health Organization (WHO) and Memorial Sloan Kettering Cancer Center (MSKCC) classification. A random-effects model was used for the pooled proportion analysis. Meta-regression analysis was conducted to evaluate the prognostic factors.
Results
Twenty retrospective studies published between 2007 and 2023, including 1,294 patients, met all inclusion criteria. Studies that diagnosed PDTC based on various histological criteria including 3rd WHO (n=5), 4th WHO (n=12), 5th WHO (n=2), and MSKCC (n=1) were included. Overall, 5-year DFS and 5-year OS were 49.4% (95% confidence interval [CI], 42.3 to 56.4) and 73.8% (95% CI, 66.5 to 79.9), with moderate heterogeneity of 58% and 55%, respectively. In meta-regression analysis, extrathyroidal extension (ETE) was a prognostic factor for OS.
Conclusion
The meta-analysis of DFS and OS in patients with PDTC show the moderate heterogeneity with a variety of histological criteria. ETE appears to have a significant impact on OS, regardless of histological criteria.

Citations

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Aggressive Types of Malignant Thyroid Neoplasms
Maria Boudina, Eleana Zisimopoulou, Persefoni Xirou, Alexandra Chrisoulidou
Journal of Clinical Medicine.2024; 13(20): 6119. CrossRef

Thyroid
Clinical Characteristics and Prognosis of Coexisting Thyroid Cancer in Patients with Graves’ Disease: A Retrospective Multicenter Study: Jee Hee Yoon, Meihua Jin, Mijin Kim, A Ram Hong, Hee Kyung Kim, Bo Hyun Kim, Won Bae Kim, Young Kee Shong, Min Ji Jeon, Ho-Cheol Kang; Endocrinol Metab. 2021;36(6):1268-1276. Published online November 26, 2021; DOI: https://doi.org/10.3803/EnM.2021.1227

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Background
The association between Graves’ disease (GD) and co-existing thyroid cancer is still controversial and most of the previously reported data have been based on surgically treated GD patients. This study investigated the clinicopathological findings and prognosis of concomitant thyroid cancer in GD patients in the era of widespread application of ultrasonography.
Methods
Data of GD patients who underwent thyroidectomy for thyroid cancer between 2010 and 2019 in three tertiary hospitals in South Korea (Asan Medical Center, Chonnam National University Hwasun Hospital, and Pusan National University Hospital) were collected and analyzed retrospectively. In the subgroup analysis, aggressiveness and clinical outcomes of thyroid cancer were compared nodular GD and non-nodular GD groups according to the presence or absence of the thyroid nodules other than thyroid cancer (index nodules).
Results
Of the 15,159 GD patients treated at the hospitals during the study period, 262 (1.7%) underwent thyroidectomy for coexisting thyroid cancer. Eleven patients (4.2%) were diagnosed with occult thyroid cancer and 182 patients (69.5%) had microcarcinomas. No differences in thyroid cancer aggressiveness, ultrasonographic findings, or prognosis were observed between the nodular GD and non-nodular GD groups except the cancer subtype. In the multivariate analysis, only lymph node (LN) metastasis was an independent prognostic factor for recurrent/persistent disease of thyroid cancer arising in GD (P=0.020).
Conclusion
The prevalence of concomitant thyroid cancer in GD patients was considerably lower than in previous reports. The clinical outcomes of thyroid cancer in GD patients were also excellent but, more cautious follow-up is necessary for patients with LN metastasis in the same way as for thyroid cancer in non-GD patients.

Citations

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Comparison of Surgical Outcomes of Transoral Versus Open Thyroidectomy for Graves Disease
Suo-Hsien Wang, Wu-Po Chao, Ta-You Lo, Soh-Ching Ng, Yu-Hsien Chen
Surgical Laparoscopy, Endoscopy & Percutaneous Techniques.2024; 34(2): 150. CrossRef
Characterization of Immune Infiltrate Along the Leading Edge of Differentiated Thyroid Cancer
Anupam Kotwal, Krysten Vance, Kemal Hajric, Ana Yuil-Valdes, Benjamin Swanson, Ernesto Martinez Duarte, Oleg Shats, Michael Hollingsworth, Hamid Band, Whitney Goldner
Thyroid®.2024; 34(8): 999. CrossRef
The Role of Risk Factors for the Progression of Patients with T1b-T2 Papillary Thyroid Carcinoma (PC) during Long-Term Follow-Up
Andrea Marongiu, Susanna Nuvoli, Andrea De Vito, Antonio Mura, Sonia Vargiu, Angela Spanu, Giuseppe Madeddu
Journal of Clinical Medicine.2024; 13(18): 5373. CrossRef
Outcomes of Surgical Treatment for Graves’ Disease: A Single-Center Experience of 216 Cases
Hanxing Sun, Hui Tong, Xiaohui Shen, Haoji Gao, Jie Kuang, Xi Chen, Qinyu Li, Weihua Qiu, Zhuoran Liu, Jiqi Yan
Journal of Clinical Medicine.2023; 12(4): 1308. CrossRef
Cancer and Mortality Risks of Graves’ Disease in South Korea Based on National Data from 2010 to 2019
Young Ju Choi, Kyungdo Han, Won Kyoung Cho, Min Ho Jung, Byung-Kyu Suh
Clinical Epidemiology.2023; Volume 15: 535. CrossRef
Risk and Prognosis of Thyroid Cancer in Patients with Graves’ Disease: An Umbrella Review
Marco Palella, Francesca Maria Giustolisi, Adriana Modica Fiascaro, Martina Fichera, Antonella Palmieri, Rossella Cannarella, Aldo E. Calogero, Margherita Ferrante, Maria Fiore
Cancers.2023; 15(10): 2724. CrossRef
Characteristics, staging and outcomes of differentiated thyroid cancer in patients with and without Graves’ disease
Chaitra Gopinath, Hanna Crow, Sujata Panthi, Leonidas Bantis, Kenneth D. Burman, Chitra Choudhary
Journal of Clinical & Translational Endocrinology.2023; 33: 100321. CrossRef
Prevalence, Treatment Status, and Comorbidities of Hyperthyroidism in Korea from 2003 to 2018: A Nationwide Population Study
Hwa Young Ahn, Sun Wook Cho, Mi Young Lee, Young Joo Park, Bon Seok Koo, Hang-Seok Chang, Ka Hee Yi
Endocrinology and Metabolism.2023; 38(4): 436. CrossRef
Hashimoto’s Thyroiditis and Papillary Thyroid Carcinoma: A Follow-Up Study in Patients with Absence of Aggressive Risk Factors at the Surgery of the Primary Tumor
Andrea Marongiu, Susanna Nuvoli, Andrea De Vito, Sonia Vargiu, Angela Spanu, Giuseppe Madeddu
Diagnostics.2023; 13(19): 3068. CrossRef
Table of Contents

Clinical Thyroidology.2022; 34(2): 48. CrossRef
Predisposition to and Prognosis of Thyroid Cancer May Not Be Affected by Graves’ Disease, But Some Questions Still Remain
Yanrui Huang, Haixia Guan
Clinical Thyroidology.2022; 34(2): 59. CrossRef
A Comparative Follow-Up Study of Patients with Papillary Thyroid Carcinoma Associated or Not with Graves’ Disease
Andrea Marongiu, Susanna Nuvoli, Andrea De Vito, Maria Rondini, Angela Spanu, Giuseppe Madeddu
Diagnostics.2022; 12(11): 2801. CrossRef
An unusual case of papillary thyroid carcinoma presenting as Graves’ disease
Pooja Tiwari, Uma Kaimal Saikia, Abhamoni Baro, Ashok Krishna Bhuyan
Thyroid Research and Practice.2022; 19(1): 47. CrossRef
An unusual case of papillary thyroid carcinoma presenting as Graves’ disease
Pooja Tiwari, Uma Kaimal Saikia, Abhamoni Baro, Ashok Krishna Bhuyan
Thyroid Research and Practice.2021; 18(3): 129. CrossRef

Thyroid
Clinicopathological Characteristics and Disease-Free Survival in Patients with Hürthle Cell Carcinoma: A Multicenter Cohort Study in South Korea: Meihua Jin, Eun Sook Kim, Bo Hyun Kim, Hee Kyung Kim, Yea Eun Kang, Min Ji Jeon, Tae Yong Kim, Ho-Cheol Kang, Won Bae Kim, Young Kee Shong, Mijin Kim, Won Gu Kim; Endocrinol Metab. 2021;36(5):1078-1085. Published online October 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1151

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Background
Hürthle cell carcinoma (HCC), a type of thyroid carcinoma, is rare in South Korea, and few studies have investigated its prognosis.
Methods
This long-term multicenter retrospective cohort study evaluated the clinicopathological features and clinical outcomes in patients with HCC who underwent thyroid surgery between 1996 and 2009.
Results
The mean age of the 97 patients included in the study was 50.3 years, and 26.8% were male. The mean size of the primary tumor was 3.2±1.8 cm, and three (3.1%) patients had distant metastasis at initial diagnosis. Ultrasonographic findings were available for 73 patients; the number of nodules with low-, intermediate-, and high suspicion was 28 (38.4%), 27 (37.0%), and 18 (24.7%), respectively, based on the Korean-Thyroid Imaging Reporting and Data System. Preoperatively, follicular neoplasm (FN) or suspicion for FN accounted for 65.2% of the cases according to the Bethesda category, and 13% had malignancy or suspicious for malignancy. During a median follow-up of 8.5 years, eight (8.2%) patients had persistent/recurrent disease, and none died of HCC. Older age, gross extrathyroidal extension (ETE), and widely invasive types of tumors were significantly associated with distant metastasis (all P<0.01). Gross ETE (hazard ratio [HR], 27.7; 95% confidence interval [CI], 2.2 to 346.4; P=0.01) and widely invasive classification (HR, 6.5; 95% CI, 1.1 to 39.4; P=0.04) were independent risk factors for poor disease-free survival (DFS).
Conclusion
The long-term prognosis of HCC is relatively favorable in South Korea from this study, although this is not a nation-wide data, and gross ETE and widely invasive cancer are significant prognostic factors for DFS. The diagnosis of HCC by ultrasonography and cytopathology remains challenging.

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Prognostic impact of fibrosclerotic changes in non-papillary, non-anaplastic, follicular cell-derived thyroid carcinomas
Giulia Orlando, Giulia Capella, Giulia Vocino Trucco, Elena Vissio, Jasna Metovic, Francesca Maletta, Marco Volante, Mauro Papotti
Virchows Archiv.2025;[Epub] CrossRef
Molecular Alterations and Comprehensive Clinical Management of Oncocytic Thyroid Carcinoma
Lindsay A. Bischoff, Ian Ganly, Laura Fugazzola, Erin Buczek, William C. Faquin, Bryan R. Haugen, Bryan McIver, Caitlin P. McMullen, Kate Newbold, Daniel J. Rocke, Marika D. Russell, Mabel Ryder, Peter M. Sadow, Eric Sherman, Maisie Shindo, David C. Shonk
JAMA Otolaryngology–Head & Neck Surgery.2024; 150(3): 265. CrossRef
Oncocytic carcinoma of the thyroid: Conclusions from a 20‐year patient cohort
Nelson R. Gruszczynski, Shahzeb S. Hasan, Ana G. Brennan, Julian De La Chapa, Adithya S. Reddy, David N. Martin, Prem P. Batchala, Edward B. Stelow, Eric M. Dowling, Katherine L. Fedder, Jonathan C. Garneau, David C. Shonka
Head & Neck.2024; 46(8): 2042. CrossRef
Oncocytic cell carcinoma of the thyroid with TERT promoter mutation presenting as asphyxia in an elderly: a case report
Xiqian Wang, Yingao Liu, Lijie Chen, Jie Zhang, Ruoyu Jiang, Lei Zhang, Han Yan, Jie Zhang
Frontiers in Endocrinology.2024;[Epub] CrossRef
Clinical Considerations of Oncocytic Thyroid Cancer: A Review
Soo Young Kim
Journal of Endocrine Surgery.2024; 24(3): 49. CrossRef
Mitochondrial Proteome Defined Molecular Pathological Characteristics of Oncocytic Thyroid Tumors
Lu Li, Likun Zhang, Wenhao Jiang, Zhiqiang Gui, Zhihong Wang, Hao Zhang, Yi He, Yi Zhu, Tiannan Guo, Haixia Guan, Zhiyan Liu, Yaoting Sun, Jianqing Gao
Endocrine Pathology.2024; 35(4): 442. CrossRef
Hurthle cell carcinoma: a rare variant of thyroid malignancy – a case report
Yuvraj Adhikari, Anupama Marasini, Nawaraj Adhikari, Laxman D. Paneru, Binit Upadhaya Regmi, Manita Raut
Annals of Medicine & Surgery.2023; 85(5): 1940. CrossRef
Hürthle Cell Carcinoma: Single Center Analysis and Considerations for Surgical Management Based on the Recent Literature
Costanza Chiapponi, Milan J.M. Hartmann, Matthias Schmidt, Michael Faust, Christiane J. Bruns, Anne M. Schultheis, Hakan Alakus
Frontiers in Endocrinology.2022;[Epub] CrossRef

Thyroid
Clinicopathological Characteristics and Recurrence-Free Survival of Rare Variants of Papillary Thyroid Carcinomas in Korea: A Retrospective Study: Mijin Kim, Sun Wook Cho, Young Joo Park, Hwa Young Ahn, Hee Sung Kim, Yong Joon Suh, Dughyun Choi, Bu Kyung Kim, Go Eun Yang, Il-Seok Park, Ka Hee Yi, Chan Kwon Jung, Bo Hyun Kim; Endocrinol Metab. 2021;36(3):619-627. Published online June 10, 2021; DOI: https://doi.org/10.3803/EnM.2021.974

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Background
We aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants.
Methods
We retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence.
Results
Rare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS.
Conclusion
In this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.

Citations

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Nomogram predicts cervical lymph node metastasis of pathological subtypes of papillary thyroid carcinoma
Ziyu Luo, Wenhan Li, Binliang Huo, Jianhui Li
Langenbeck's Archives of Surgery.2024;[Epub] CrossRef
Serum thyroglobulin testing after thyroid lobectomy in patients with 1–4 cm papillary thyroid carcinoma
Ahreum Jang, Meihua Jin, Chae A Kim, Min Ji Jeon, Yu-Mi Lee, Tae-Yon Sung, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Won Gu Kim
Endocrine.2023; 81(2): 290. CrossRef
Do Histologically Aggressive Subtypes of Papillary Thyroid Microcarcinoma have Worse Clinical Outcome than Non-Aggressive Papillary Thyroid Microcarcinoma Subtypes? A Multicenter Cohort Study
Sayid Shafi Zuhur, Hunkar Aggul, Ugur Avci, Selvinaz Erol, Mazhar Müslüm Tuna, Serhat Uysal, Gulhan Akbaba, Faruk Kilinç, Merve Catak, Sakin Tekin, Ogun Irem Bilen, Beyza Olcay Öztürk, Ecem Bilgehan Erden, Gulsah Elbuken, Halise Cinar Yavuz, Pinar Kadiogl
Hormone and Metabolic Research.2023; 55(05): 323. CrossRef
The Warthin-like variant of papillary thyroid carcinomas: a clinicopathologic analysis report of two cases
Xing Zhao, Yijia Zhang, Pengyu Hao, Mingzhen Zhao, Xingbin Shen
Oncologie.2023; 25(5): 581. CrossRef
A Retrospective Cohort Study with Validation of Predictors of Differentiated Thyroid Cancer Outcomes
Ayanthi Wijewardene, Anthony J. Gill, Matti Gild, Diana L. Learoyd, Anthony Robert Glover, Mark Sywak, Stan Sidhu, Paul Roach, Geoffrey Schembri, Jeremy Hoang, Bruce Robinson, Lyndal Tacon, Roderick Clifton-Bligh
Thyroid.2022;[Epub] CrossRef
Clinicopathological Implications of the BRAFV600E Mutation in Papillary Thyroid Carcinoma of Ukrainian Patients Exposed to the Chernobyl Radiation in Childhood: A Study for 30 Years After the Accident
Liudmyla Zurnadzhy, Tetiana Bogdanova, Tatiana I. Rogounovitch, Masahiro Ito, Mykola Tronko, Shunichi Yamashita, Norisato Mitsutake, Michael Bolgov, Serhii Chernyshov, Sergii Masiuk, Vladimir A. Saenko
Frontiers in Medicine.2022;[Epub] CrossRef

Clinical Study
Lactate Dehydrogenase A as a Potential New Biomarker for Thyroid Cancer: Eun Jeong Ban, Daham Kim, Jin Kyong Kim, Sang-Wook Kang, Jandee Lee, Jong Ju Jeong, Kee-Hyun Nam, Woong Youn Chung, Kunhong Kim; Endocrinol Metab. 2021;36(1):96-105. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.819

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Background
Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV^600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker.
Methods
LDHA expression was examined in 83 PTC tissue specimens by immunohistochemistry. Human thyroid cell lines were genetically manipulated to overexpress BRAFV^600E or were treated with a BRAF-specific short hairpin RNA (shBRAF), whose effects on LDHA expression were evaluated by Western blotting. Data from 465 PTC patients were obtained from The Cancer Genome Atlas (TCGA) database and analyzed to validate the in vitro results.
Results
LDHA was aberrantly overexpressed in PTC. Intense immunostaining for LDHA was observed in PTC specimens carrying mutated BRAF, whereas the intensity was less in wild-type BRAF samples. Overexpression of BRAFV^600E resulted in LDHA upregulation, whereas treatment with shBRAF downregulated LDHA in human thyroid cell lines. Furthermore, LDHA mRNA expression was significantly elevated and associated with BRAFV^600E expression in thyroid cancer tissues from TCGA database. Additionally, LDHA overexpression was found to be correlated with aggressive clinical features of PTC, such as lymph node metastases and advanced tumor stages.
Conclusion
LDHA overexpression is associated with the BRAFV^600E mutation and an aggressive PTC behavior. Therefore, LDHA may serve as a biomarker and therapeutic target in PTC.

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Integrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks
Ning Qu, Di Chen, Ben Ma, Lijun Zhang, Qiuping Wang, Yuting Wang, Hongping Wang, Zhaoxian Ni, Wen Wang, Tian Liao, Jun Xiang, Yulong Wang, Shi Jin, Dixin Xue, Weili Wu, Yu Wang, Qinghai Ji, Hui He, Hai-long Piao, Rongliang Shi
Nature Communications.2024;[Epub] CrossRef
Fibroblast growth factor pathway promotes glycolysis by activating LDHA and suppressing LDHB in a STAT1-dependent manner in prostate cancer
Yongkang Ye, Fukan Yang, Zhanhao Gu, Wenxuan Li, Yinjiao Yuan, Shaoqian Liu, Le Zhou, Bo Han, Ruinian Zheng, Zhengguo Cao
Journal of Translational Medicine.2024;[Epub] CrossRef
Lactate Dehydrogenase A is Associated with Elevated FDG Metabolism, Radioiodine Non-avidity, and Poor Prognosis in Differentiated Thyroid Cancer
Tian Tian, Hongyuan Dai, Mengni Zhang, Minggang Su, Xueqin Chen, Rui Huang
Academic Radiology.2024; 31(10): 4011. CrossRef
Peripheral lymphocytes and lactate dehydrogenase correlate with response and survival in head and neck cancers treated with immune checkpoint inhibitors
Cassie Pan, Qian Vicky Wu, Jenna Voutsinas, Jeffrey J. Houlton, Brittany Barber, Zain H. Rizvi, Emily Marchiano, Neal Futran, George E. Laramore, Jay J. Liao, Upendra Parvathaneni, Renato G. Martins, Jonathan R. Fromm, Cristina P. Rodriguez
Cancer Medicine.2023; 12(8): 9384. CrossRef
LncRNA GLTC targets LDHA for succinylation and enzymatic activity to promote progression and radioiodine resistance in papillary thyroid cancer
Liang Shi, Rui Duan, Zhenhua Sun, Qiong Jia, Wenyu Wu, Feng Wang, Jianjun Liu, Hao Zhang, Xue Xue
Cell Death & Differentiation.2023; 30(6): 1517. CrossRef
Integrated analysis of circulating and tissue proteomes reveals that fibronectin 1 is a potential biomarker in papillary thyroid cancer
Guochao Ye, Xiaomei Zhang, Mansheng Li, Zixiang Lin, Yongcan Xu, Haoru Dong, Jie Zhou, Jiaqi Zhang, Sheng Wang, Yunping Zhu, Xiaobo Yu, Xu Qian
BMC Cancer.2023;[Epub] CrossRef
Targeting metabolism by B-raf inhibitors and diclofenac restrains the viability of BRAF-mutated thyroid carcinomas with Hif-1α-mediated glycolytic phenotype
Marianna Aprile, Simona Cataldi, Caterina Perfetto, Antonio Federico, Alfredo Ciccodicola, Valerio Costa
British Journal of Cancer.2023; 129(2): 249. CrossRef
circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
Hongguo Xie, Xiaopeng Lu
Open Medicine.2023;[Epub] CrossRef
The potential role of reprogrammed glucose metabolism: an emerging actionable codependent target in thyroid cancer
Sai-li Duan, Min Wu, Zhe-Jia Zhang, Shi Chang
Journal of Translational Medicine.2023;[Epub] CrossRef
CENPE and LDHA were potential prognostic biomarkers of chromophobe renal cell carcinoma
Hui-feng Wu, Hao Liu, Zhe-wei Zhang, Ji-min Chen
European Journal of Medical Research.2023;[Epub] CrossRef
Classification for Staging and Managing Patients with Biopolymer-induced Human Adjuvant Disease
Jaime Eduardo Pachón Suárez, Marcela C. Salazar, Victor Z. Rizo
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Development of Metabolic Synthetic Lethality and Its Implications for Thyroid Cancer
Sang-Hyeon Ju, Seong Eun Lee, Yea Eun Kang, Minho Shong
Endocrinology and Metabolism.2022; 37(1): 53. CrossRef
Drug delivery for metabolism targeted cancer immunotherapy
Taravat Khodaei, Sahil Inamdar, Abhirami P. Suresh, Abhinav P. Acharya
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Sulfur quantum dot based fluorescence assay for lactate dehydrogenase activity detection
Shengnan Fan, Xiaoqing Li, Fanghui Ma, Minghui Yang, Juan Su, Xiang Chen
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STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysis
Nan Huo, Rui Cong, Zhi-jia Sun, Wen-chao Li, Xiang Zhu, Chun-yuan Xue, Zhao Chen, Lu-yuan Ma, Zhong Chu, Yu-chen Han, Xiao-feng Kang, Song-hao Jia, Nan Du, Lei Kang, Xiao-jie Xu
Cell Death & Disease.2021;[Epub] CrossRef
80MAP17 promotes the tumorigenesis of papillary thyroid carcinoma by reducing the stability of p53
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Frontiers in Bioscience-Landmark.2021;[Epub] CrossRef

Review Article

Thyroid
Updates in the Pathologic Classification of Thyroid Neoplasms: A Review of the World Health Organization Classification: Yanhua Bai, Kennichi Kakudo, Chan Kwon Jung; Endocrinol Metab. 2020;35(4):696-715. Published online December 2, 2020; DOI: https://doi.org/10.3803/EnM.2020.807

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Advances in medical sciences and evidence-based medicine have led to momentous changes in classification and management of thyroid neoplasms. Much progress has been made toward avoiding overdiagnosis and overtreatment of thyroid cancers. The new 2017 World Health Organization (WHO) classification of thyroid neoplasms updated the diagnostic criteria and molecular and genetic characteristics reflecting the biology and behavior of the tumors, and newly introduced the category of borderline malignancy or uncertain malignant potential. Some neoplasms were subclassified, renamed, or redefined as a specific entity. This review introduces changes in the fourth edition WHO classification of thyroid tumors and updates the contemporary diagnosis and classification of thyroid tumors. We also discuss several challenges with the proposal of new diagnostic entities, since they have unique histopathologic and molecular features and clinical relevance.

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Original Articles

Clinical Study
Clinical Outcomes after Early and Delayed Radioiodine Remnant Ablation in Patients with Low-Risk Papillary Thyroid Carcinoma: Propensity Score Matching Analysis: Jonghwa Ahn, Meihua Jin, Eyun Song, Min Ji Jeon, Tae Yong Kim, Jin-Sook Ryu, Won Bae Kim, Young Kee Shong, Ji Min Han, Won Gu Kim; Endocrinol Metab. 2020;35(4):830-837. Published online November 18, 2020; DOI: https://doi.org/10.3803/EnM.2020.747

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Background
The clinical outcomes of delayed radioiodine remnant ablation (RRA) therapy in patients with low-risk papillary thyroid carcinoma (PTC) are unclear. We aimed to evaluate the clinical impact of the interval between total thyroidectomy (TT) and RRA therapy in patients with low-risk PTC.
Methods
We included 526 patients who underwent TT and RRA for low-risk PTC with a primary tumor size of >1 cm between 2000 and 2012. Patients were divided into the early (<90 days) and the delayed (≥90 days) RRA groups based on the interval between TT and RRA. The results of diagnostic whole-body scan (DxWBS), ongoing risk stratification (ORS; response to therapy), and disease-free survival (DFS) were evaluated before and after propensity score matching (PSM).
Results
Among the 526 patients, 75 (14.3%) patients underwent delayed RRA; they had more cervical lymph node metastasis and received a higher RRA dose than those who underwent early RRA. The median follow-up period was 9.1 years after initial therapy, and the structural recurrence rate was 1.9%. In DxWBS, 60 patients had focal iodine uptake limited in operative bed, with no significant difference between groups. According to ORS, 78%, 20%, 1%, and 1% patients were classified into excellent, indeterminate, biochemical incomplete, and structural incomplete response groups, respectively. There was no significant difference in ORS or DFS between groups before and after PSM.
Conclusion
The timing of the first RRA had no clinical impact in patients with low-risk PTC. Thus, the clinical decision for RRA can be determined >3 months after TT considering other prognostic factors.

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Dynamic risk assessment in patients with differentiated thyroid cancer
Erika Abelleira, Fernando Jerkovich
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Ablation Rates and Long-Term Outcome Following Low-Dose Radioiodine for Differentiated Thyroid Cancer in the West of Scotland: A Retrospective Analysis
Kathryn Graham, Fay Tough, Helena Belikova, Irene Wotherspoon, David Colville, Nicholas Reed
Endocrine Practice.2024; 30(4): 327. CrossRef
Radioiodine ablation after thyroidectomy could be safely abandoned or postponed in selected stage I papillary thyroid carcinoma patients of low-risk group: an observational prospective study
S.M. Cherenko, A.Yu. Glagolieva, D.E. Makhmudov
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Endocrine Research
Liver X Receptor β Related to Tumor Progression and Ribosome Gene Expression in Papillary Thyroid Cancer: Seonhyang Jeong, In-Kyu Kim, Hyunji Kim, Moon Jung Choi, Jandee Lee, Young Suk Jo; Endocrinol Metab. 2020;35(3):656-668. Published online August 20, 2020; DOI: https://doi.org/10.3803/EnM.2020.667

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Background
Intracellular lipid deposition has been reported in thyroid glands in obese animal and human. To understand the regulatory mechanism of lipid metabolism in thyroid cancer, we investigated the expression status of liver X receptor (LXR) and analyzed its clinicopathological characteristics and molecular biological features.
Methods
Expression status of LXR and its transcriptional targets in human cancers were analyzed using The Cancer Genome Atlas (TCGA). The gene-sets related to high LXRβ expression was investigated by gene set enrichment analysis (GSEA) using Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and gene ontology biologic process. Quantitative reverse transcription polymerase chain reaction was performed in thyroid cancer samples using our validation cohort.
Results
In contrast to low expression of LXRα, LXRβ was highly expressed in thyroid cancer compared to the other types of human cancers. High LXRβ expression was correlated with the expression of LXRβ transcriptional targets genes, such as apolipoprotein C1 (APOC1), APOC2, apolipoprotein E (APOE), ATP binding cassette subfamily G member 8 (ABCG8), sterol regulatory elementbinding protein 1c (SREBP1c), and SPOT14. Furthermore, High LXRβ expression group indicated poor clinicopathological characteristics and aggressive molecular biological features independently from the drive mutation status. Mechanistically, high LXRβ expression was coordinately related to ribosome-related gene sets.
Conclusion
The mechanistic link between LXRβ and ribosomal activity will be addressed to develop new diagnostic and therapeutic targets in thyroid cancers.

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Nour M. Darwish, Mooza Kh. Al-Hail, Youssef Mohamed, Rafif Al Saady, Sara Mohsen, Amna Zar, Layla Al-Mansoori, Shona Pedersen
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Simultaneous Expression of Long Non-Coding RNA FAL1 and Extracellular Matrix Protein 1 Defines Tumour Behaviour in Young Patients with Papillary Thyroid Cancer
Seonhyang Jeong, Seul-Gi Lee, Hyunji Kim, Gibbeum Lee, Sunmi Park, In-Kyu Kim, Jandee Lee, Young-Suk Jo
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Giuseppe Agapito, Mario Cannataro
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Mian Liu, Rooh Afza Khushbu, Pei Chen, Hui-Yu Hu, Neng Tang, Deng-jie Ou-yang, Bo Wei, Ya-xin Zhao, Peng Huang, Shi Chang
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Lisha Bao, Tong Xu, Xixuan Lu, Ping Huang, Zongfu Pan, Minghua Ge
Frontiers in Oncology.2021;[Epub] CrossRef
Cooperative Subtype Switch of Thyroid Hormone Receptor and Nuclear Receptor Corepressor Related Epithelial–Mesenchymal Transition in Papillary Thyroid Cancer
Seonhyang Jeong, Seul Gi Lee, Hyunji Kim, Gibbeum Lee, Sunmi Park, In-Kyu Kim, Jandee Lee, Young Suk Jo
International Journal of Thyroidology.2021; 14(2): 152. CrossRef

Clinical Study
Development and Validation of a Risk Scoring System Derived from Meta-Analyses of Papillary Thyroid Cancer: Sunghwan Suh, Tae Sik Goh, Yun Hak Kim, Sae-Ock Oh, Kyoungjune Pak, Ju Won Seok, In Joo Kim; Endocrinol Metab. 2020;35(2):435-442. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.435; Correction in: Endocrinol Metab 2023;38(2):287

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Background
The aim of this study was to develop a scoring system to stratify the risk of papillary thyroid cancer (PTC) and to select the proper management.
Methods
We performed a systematic search of MEDLINE and Embase. Data regarding patients’ prognoses were obtained from the included studies. Odds ratios (ORs) with statistical significance were extracted from the publications. To generate a risk scoring system (RSS), ORs were summed (RSS1), and summed after natural-logarithmic transformation (RSS2). RSS1 and RSS2 were compared to the eighth edition of the American Joint Committee on Cancer (AJCC) staging system and the 2015 American Thyroid Association (ATA) guidelines for thyroid nodules and differentiated thyroid carcinoma.
Results
Five meta-analyses were eligible for inclusion in the study. Eight variables (sex, tumour size, extrathyroidal extension, BRAF mutation, TERT mutation, histologic subtype, lymph node metastasis, and distant metastasis) were included. RSS1 was the best of the analysed models.
Conclusion
We developed and validated a new RSS derived from previous meta-analyses for patients with PTC. This RSS seems to be superior to previously published systems.

Citations

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Devan Diwanji, Emmanuel Carrodeguas, Youngho Seo, Hyunseok Kang, Myat Han Soe, Janet M. Chiang, Li Zhang, Chienying Liu, Spencer C. Behr, Robert R. Flavell
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Clinical Study
Subclinical Hypothyroidism Affects the Long-Term Outcomes of Patients Who Undergo Coronary Artery Bypass Grafting Surgery but Not Heart Valve Surgery: Hana Kim, Sung Hye Kong, Jae Hoon Moon, Sang Yoon Kim, Kay-Hyun Park, Jun Sung Kim, Joong Haeng Choh, Young Joo Park, Cheong Lim; Endocrinol Metab. 2020;35(2):308-318. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.308

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Background
The aim of this study was to determine the associations between subclinical hypothyroidism (SCH) and long-term cardiovascular outcomes after coronary artery bypass grafting (CABG) or heart valve surgery (HVS).
Methods
We retrospectively reviewed and compared all-cause mortality, cardiovascular mortality, and cardiovascular events in 461 patients who underwent CABG and 104 patients who underwent HVS.
Results
During a mean±standard deviation follow-up duration of 7.6±3.8 years, there were 187 all-cause deaths, 97 cardiovascular deaths, 127 major adverse cardiovascular events (MACE), 11 myocardial infarctions, one unstable angina, 70 strokes, 30 hospitalizations due to heart failure, 101 atrial fibrillation, and 33 coronary revascularizations. The incidence of all-cause mortality after CABG was significantly higher in patients with SCH (n=36, 55.4%) than in euthyroid patients (n=120, 30.3%), with a hazard ratio of 1.70 (95% confidence interval, 1.10 to 2.63; P=0.018) after adjustment for age, sex, current smoking status, body mass index, underlying diseases, left ventricular dysfunction, and emergency operation. Interestingly, low total triiodothyronine (T3) levels in euthyroid patients who underwent CABG were significantly associated with increased risks of all-cause mortality, cardiovascular mortality, and MACE, but those associations were not observed in HVS patients. Both free thyroxine and thyroid-stimulating hormone levels in euthyroid patients were not related with any cardiovascular outcomes in either the CABG or HVS group.
Conclusion
SCH or low total T3 might be associated with a poor prognosis after CABG, but not after HVS, implying that preoperative thyroid hormonal status may be important in ischemic heart disease patients.

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Subclinical hypothyroidism and clinical outcomes after cardiac surgery: A systematic review and meta-analysis
Michele Dell’Aquila, Camilla S. Rossi, Tulio Caldonazo, Gianmarco Cancelli, Lamia Harik, Giovanni J. Soletti, Kevin R. An, Jordan Leith, Hristo Kirov, Mudathir Ibrahim, Michelle Demetres, Arnaldo Dimagli, Mohamed Rahouma, Mario Gaudino
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The Journal of Cardiovascular Surgery.2024;[Epub] CrossRef
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Mid-term outcomes of patients with subclinical hypothyroidism after coronary bypass surgery
Dong Zhao, Wei Zhao, Chuangshi Wang, Fei Xu, Wei Zhao, Xieraili Tiemuerniyazi, Hao Ma, Wei Feng
Interdisciplinary CardioVascular and Thoracic Surgery.2023;[Epub] CrossRef
Thyroid Pathology in High-Risk Cardiac Surgery Patients with Coronary Artery Disease
Olena K. Gogayeva, Anatoliy V. Rudenko, Vasyl V. Lazoryshynets, Serhii A. Rudenko, Tetiana A. Andrushchenko
Ukrainian Journal of Cardiovascular Surgery.2022; 30(1 (46)): 9. CrossRef
High-TSH Subclinical Hypothyroidism Is Associated With Postoperative Mortality in Acute Type A Aortic Dissection
Shi-Pan Wang, Yuan Xue, Hai-Yang Li, Wen-Jian Jiang, Hong-Jia Zhang
Frontiers in Endocrinology.2022;[Epub] CrossRef
Triiodothyronine improves contractile recovery of human atrial trabeculae after hypoxia/reoxygenation
Petra Kleinbongard, Philipp Kuthan, Chantal Eickelmann, Philipp Jakobs, Joachim Altschmied, Judith Haendeler, Arjang Ruhparwar, Matthias Thielmann, Gerd Heusch
International Journal of Cardiology.2022; 363: 159. CrossRef
Hypothyroidism Is Correlated with Ventilator Complications and Longer Hospital Days after Coronary Artery Bypass Grafting Surgery in a Relatively Young Population: A Nationwide, Population-Based Study
Jiun-Yu Lin, Pei-Chi Kao, Yi-Ting Tsai, Chi-Hsiang Chung, Wu-Chien Chien, Chih-Yuan Lin, Chieh-Hua Lu, Chien-Sung Tsai
Journal of Clinical Medicine.2022; 11(13): 3881. CrossRef
Minor perturbations of thyroid homeostasis and major cardiovascular endpoints—Physiological mechanisms and clinical evidence
Patrick Müller, Melvin Khee-Shing Leow, Johannes W. Dietrich
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Subclinical Hypothyroidism: Prevalence, Health Impact, and Treatment Landscape
Won Sang Yoo, Hyun Kyung Chung
Endocrinology and Metabolism.2021; 36(3): 500. CrossRef

Clinical Study
Epidemiology and Prognosis of Pheochromocytoma/Paraganglioma in Korea: A Nationwide Study Based on the National Health Insurance Service: Jung Hee Kim, Hyemi Moon, Junghyun Noh, Juneyoung Lee, Sin Gon Kim; Endocrinol Metab. 2020;35(1):157-164. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.157

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Background

Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors originating from chromaffin cells. PPGLs are associated with a high mortality rate and several complications. To date, no epidemiological studies have been conducted on PPGLs in Asia. This study aimed to investigate the epidemiology and prognosis of PPGLs in Korea using nationwide data.

Methods

Using the National Health Insurance Service Database, subjects with a principal diagnosis of PPGLs on two or more occasions between 2003 and 2014 who satisfied the operational definition of PPGLs were included. Incidence, prevalence, complications, metastasis, and mortality were investigated.

Results

In total, 1048 subjects with a mean age of 47.6±16.1 years were included. There was no sex preponderance. The overall prevalence of PPGLs was 2.13 per 100,000 persons, and the overall age-standardized incidence rate was 0.18 per 100,000 person-years. Malignant PPGLs accounted for 17.7% (185 of 1,048) of cases, and 94 subjects exhibited metastasis at the time of diagnosis. Among initially non-metastatic PPGLs, 9.5% (nine of 954) eventually metastasized after a mean duration of 78.1±41.4 months. The 5-year survival rates for non-metastatic and metastatic PPGLs at diagnosis were 97% and 84%, respectively. Multivariable Cox regression models adjusted for covariates showed that metastatic PPGLs were associated with a 2.40-fold higher risk of mortality than non-metastatic PPGLs (95% confidence interval, 1.38 to 4.17; P=0.002).

Conclusion

PPGLs are rare in Korea, and the prognosis of these endocrine tumors varies depending on whether they are benign or malignant. This epidemiological study paves the way for further research on PPGLs.

Citations

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Review Article

Thyroid
Unmet Clinical Needs in the Treatment of Patients with Thyroid Cancer: Won Bae Kim, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong; Endocrinol Metab. 2020;35(1):14-25. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.14

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The increased incidence of thyroid cancer is a worldwide phenomenon; however, the issue of overdiagnosis has been most prominent in South Korea. The age-standardized mortality rate of thyroid cancer in Korea steeply increased from 1985 to 2004 (from 0.17 per 100,000 to 0.85 per 100,000), and then decreased until 2015 to 0.42 per 100,000, suggesting that early detection reduced mortality. However, early detection of thyroid cancer may be cost-ineffective, considering its very high prevalence and indolent course. Therefore, risk stratification and tailored management are vitally important, but many prognostic markers can only be evaluated postoperatively. Discovery of preoperative marker(s), especially for small cancers, is the most important unmet clinical need for thyroid cancer. Herein, we discuss some such factors that we recently discovered. Another unmet clinical need is better treatment of radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC) and undifferentiated cancers. Although sorafenib and lenvatinib are available, better drugs are needed. We found that phosphoglycerate dehydrogenase, a critical enzyme for serine biosynthesis, could be a novel therapeutic target, and that the lymphocyte-to-monocyte ratio is a prognostic marker of survival in patients with anaplastic thyroid carcinoma or RAIR DTC. Deeper insights are needed into tumor-host interactions in thyroid cancer to improve treatment.

Citations

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Lenvatinib Compared with Sorafenib as a First-Line Treatment for Radioactive Iodine-Refractory, Progressive, Differentiated Thyroid Carcinoma: Real-World Outcomes in a Multicenter Retrospective Cohort Study
Mijin Kim, Meihua Jin, Min Ji Jeon, Eui Young Kim, Dong Yeob Shin, Dong Jun Lim, Bo Hyun Kim, Ho-Cheol Kang, Won Bae Kim, Young Kee Shong, Hee Kyung Kim, Won Gu Kim
Thyroid.2023; 33(1): 91. CrossRef
Serum thyroglobulin testing after thyroid lobectomy in patients with 1–4 cm papillary thyroid carcinoma
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Fengjing Fan, Fei Li, Yixuan Wang, Zhengjun Dai, Yuyang Lin, Lin Liao, Bei Wang, Hongjun Sun
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Transcriptomic Analysis of Papillary Thyroid Cancer: A Focus on Immune-Subtyping, Oncogenic Fusion, and Recurrence
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Original Article

Clinical Study
Protein Expression of Cyclin B1, Transferrin Receptor, and Fibronectin Is Correlated with the Prognosis of Adrenal Cortical Carcinoma: Sun Joon Moon, Jung Hee Kim, Sung Hye Kong, Chan Soo Shin; Endocrinol Metab. 2020;35(1):132-141. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.132

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Background

Adrenal cortical carcinoma (ACC) is a rare cancer with a variable prognosis. Several prognostic factors of ACC have been previously reported, but a proteomic analysis has not yet been performed. This study aimed to investigate prognostic biomarkers for ACC using a proteomic approach.

Methods

We used reverse-phase protein array data from The Cancer Proteome Atlas, and identified differentially expressed proteins in metastatic ACCs. Multivariate Cox regression analysis adjusted by age and staging was used for survival analysis, and the C-index and category-free net reclassification improvement (cfNRI) were utilized to evaluate additive prognostic value.

Results

In 46 patients with ACC, cyclin B1, transferrin receptor (TfR1), and fibronectin were significantly overexpressed in patients with distant metastasis. In multivariate models, high expression of cyclin B1 and TfR1 was significantly associated with mortality (hazard ratio [HR], 6.13; 95% confidence interval [CI], 1.02 to 36.7; and HR, 6.59; 95% CI, 1.14 to 38.2; respectively), whereas high fibronectin expression was not (HR, 3.92; 95% CI, 0.75 to 20.4). Combinations of high cyclin B1/high TfR1, high cyclin B1/high fibronectin, and high TfR1/high fibronectin were strongly associated with mortality ([HR, 13.72; 95% CI, 1.89 to 99.66], [HR, 9.22; 95% CI, 1.34 to 63.55], and [HR, 18.59; 95% CI, 2.54 to 135.88], respectively). In reclassification analyses, cyclin B1, TfR1, fibronectin, and combinations thereof improved the prognostic performance (C-index, 0.78 to 0.82–0.86; cfNRI, all P values <0.05).

Conclusion

In ACC patients, the overexpression of cyclin B1, TfR1, and fibronectin and combinations thereof were associated with poor prognosis.

Citations

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