Chih-Yi Liu ^{1, 2}, Ching-Shui Huang ^{3, 4}, Chi-Cheng Huang ^{5, 6}, Wei-Chi Ku ², Hsing-Yu Shih ³, Chi-Jung Huang ^{7, 8}

Affiliations

1. Division of Pathology, Sijhih Cathay General Hospital, New Taipei City 221, Taiwan.
2. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan.
3. Division of General Surgery, Department of Surgery, Cathay General Hospital, Taipei 106, Taiwan.
4. School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
5. Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, Taipei 1121, Taiwan.
6. School of Public Health, College of Public Health, National Taiwan University, Taipei 100, Taiwan.
7. Department of Medical Research, Cathay General Hospital, Taipei 106, Taiwan.
8. Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan.

ABSTRACT

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.

Keywords: DNA mismatch repair; cell cycle; immunohistochemistry; multiple primary; neoplasms; second primary; thyroid neoplasms.

>Cancers (Basel). 2021 Oct 31;13(21):5486. doi: 10.3390/cancers13215486.