Co-Occurrence of Differentiated Thyroid Cancer and Second Primary Malignancy: Correlation with Expression Profiles of Mismatch Repair Protein and Cell Cycle Regulators

Some patients with thyroid cancer develop a second primary cancer. Defining the characteristics of patients with double primary cancers (DPCs) is crucial and needs to be followed. In this study, we examine molecular profiles in DPC. We enrolled 71 patients who received thyroid cancer surgery, 26 wit...

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Autores principales:	Chih-Yi Liu, Ching-Shui Huang, Chi-Cheng Huang, Wei-Chi Ku, Hsing-Yu Shih, Chi-Jung Huang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	thyroid neoplasms neoplasms second primary multiple primary immunohistochemistry Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/be3b775f0a1b4095801bcd57faeb0a9e
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spelling	oai:doaj.org-article:be3b775f0a1b4095801bcd57faeb0a9e2021-11-11T15:33:40ZCo-Occurrence of Differentiated Thyroid Cancer and Second Primary Malignancy: Correlation with Expression Profiles of Mismatch Repair Protein and Cell Cycle Regulators10.3390/cancers132154862072-6694https://doaj.org/article/be3b775f0a1b4095801bcd57faeb0a9e2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5486https://doaj.org/toc/2072-6694Some patients with thyroid cancer develop a second primary cancer. Defining the characteristics of patients with double primary cancers (DPCs) is crucial and needs to be followed. In this study, we examine molecular profiles in DPC. We enrolled 71 patients who received thyroid cancer surgery, 26 with single thyroid cancer (STC), and 45 with DPC. A retrograde cohort was used to develop immunohistochemical expressions of mismatch repair (MMR) proteins and cell-cycle-related markers from tissue microarrays to produce an equation for predicting the occurrence of DPC. The multivariate logistic model of 67 randomly selected patients (24 with STC and 43 with DPC) identified that the expression of deficient MMR (dMMR) (odds ratio (OR), 10.34; 95% confidence interval (CI), 2.17–49.21) and pRb (OR, 62.71; 95% CI, 4.83–814.22) were significantly associated with a higher risk of DPC. In contrast, the expression of CDK4 (OR, 0.19; 95% CI, 0.04–0.99) and CDK6 (OR, 0.03; 95% CI, 0.002–0.44) was significantly associated with a lower risk of DPC. Collectively, dMMR, pRb, CDK4, and CDK6 have a sensitivity of 88.9% (95% CI, 75.1–95.8) and a specificity of 69.2% (95% CI, 48.1–84.9) for occurrence of DPC in all 71 patients. This is the first report to demonstrate the molecular differentiation of STC and DPC. Overall, the integral molecular profile performed excellent discrimination and denoted an exponential function to predict the probability of DPC.Chih-Yi LiuChing-Shui HuangChi-Cheng HuangWei-Chi KuHsing-Yu ShihChi-Jung HuangMDPI AGarticlethyroid neoplasmsneoplasmssecond primaryneoplasmsmultiple primaryimmunohistochemistryNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5486, p 5486 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	thyroid neoplasms neoplasms second primary neoplasms multiple primary immunohistochemistry Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	thyroid neoplasms neoplasms second primary neoplasms multiple primary immunohistochemistry Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Chih-Yi Liu Ching-Shui Huang Chi-Cheng Huang Wei-Chi Ku Hsing-Yu Shih Chi-Jung Huang Co-Occurrence of Differentiated Thyroid Cancer and Second Primary Malignancy: Correlation with Expression Profiles of Mismatch Repair Protein and Cell Cycle Regulators
description	Some patients with thyroid cancer develop a second primary cancer. Defining the characteristics of patients with double primary cancers (DPCs) is crucial and needs to be followed. In this study, we examine molecular profiles in DPC. We enrolled 71 patients who received thyroid cancer surgery, 26 with single thyroid cancer (STC), and 45 with DPC. A retrograde cohort was used to develop immunohistochemical expressions of mismatch repair (MMR) proteins and cell-cycle-related markers from tissue microarrays to produce an equation for predicting the occurrence of DPC. The multivariate logistic model of 67 randomly selected patients (24 with STC and 43 with DPC) identified that the expression of deficient MMR (dMMR) (odds ratio (OR), 10.34; 95% confidence interval (CI), 2.17–49.21) and pRb (OR, 62.71; 95% CI, 4.83–814.22) were significantly associated with a higher risk of DPC. In contrast, the expression of CDK4 (OR, 0.19; 95% CI, 0.04–0.99) and CDK6 (OR, 0.03; 95% CI, 0.002–0.44) was significantly associated with a lower risk of DPC. Collectively, dMMR, pRb, CDK4, and CDK6 have a sensitivity of 88.9% (95% CI, 75.1–95.8) and a specificity of 69.2% (95% CI, 48.1–84.9) for occurrence of DPC in all 71 patients. This is the first report to demonstrate the molecular differentiation of STC and DPC. Overall, the integral molecular profile performed excellent discrimination and denoted an exponential function to predict the probability of DPC.
format	article
author	Chih-Yi Liu Ching-Shui Huang Chi-Cheng Huang Wei-Chi Ku Hsing-Yu Shih Chi-Jung Huang
author_facet	Chih-Yi Liu Ching-Shui Huang Chi-Cheng Huang Wei-Chi Ku Hsing-Yu Shih Chi-Jung Huang
author_sort	Chih-Yi Liu
title	Co-Occurrence of Differentiated Thyroid Cancer and Second Primary Malignancy: Correlation with Expression Profiles of Mismatch Repair Protein and Cell Cycle Regulators
title_short	Co-Occurrence of Differentiated Thyroid Cancer and Second Primary Malignancy: Correlation with Expression Profiles of Mismatch Repair Protein and Cell Cycle Regulators
title_full	Co-Occurrence of Differentiated Thyroid Cancer and Second Primary Malignancy: Correlation with Expression Profiles of Mismatch Repair Protein and Cell Cycle Regulators
title_fullStr	Co-Occurrence of Differentiated Thyroid Cancer and Second Primary Malignancy: Correlation with Expression Profiles of Mismatch Repair Protein and Cell Cycle Regulators
title_full_unstemmed	Co-Occurrence of Differentiated Thyroid Cancer and Second Primary Malignancy: Correlation with Expression Profiles of Mismatch Repair Protein and Cell Cycle Regulators
title_sort	co-occurrence of differentiated thyroid cancer and second primary malignancy: correlation with expression profiles of mismatch repair protein and cell cycle regulators
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/be3b775f0a1b4095801bcd57faeb0a9e
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Co-Occurrence of Differentiated Thyroid Cancer and Second Primary Malignancy: Correlation with Expression Profiles of Mismatch Repair Protein and Cell Cycle Regulators

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