Evaluation of Grade in a Genotyped Cohort of Sporadic Medullary Thyroid Carcinoma.

Najdawi, Fedaa; Ahmadi, Sara; Capelletti, Marzia; Dong, Fei; Chau, Nicole G; Barletta, Justine A

BACKGROUND Tumor grade and RET mutation status, especially presence of high-risk exon 15 and 16 RET mutations, have been reported to be prognostic in sporadic medullary thyroid carcinoma (MTC). The aim of our study was to evaluate the performance of two recently proposed grading systems and to assess the association between grade and genotype in a cohort of sporadic MTC. DESIGN We identified 44 sporadic MTC. All available tumor slides were examined, and cases were assigned a grade based on either mitotic count and tumor necrosis or mitotic count, tumor necrosis, and Ki-67 proliferative index, as described in two recent studies. Additional clinicopathologic features and outcome information were obtained from the pathology reports and electronic medical records. Presence of RET and RAS mutations were determined either by direct sequencing or massively parallel sequencing. RESULTS Both grading systems were prognostic for progression-free survival and disease-specific survival on univariate analysis. There was no correlation between grade and mutation status. Specifically, neither RET nor high-risk RET mutations were enriched in high-grade tumors, as assessed by either grading scheme. CONCLUSION Our findings suggest that grade is not correlated with RET/RAS mutation status, indicating that grade and genotype may give independent prognostic information.