Development and validation of an RNA sequencing–based classifier for medullary thyroid carcinoma on thyroid FNA

Abstract

This commentary describes the development and validation of the Afirma RNA sequencing–based classifier for medullary thyroid carcinoma (MTC). The importance of the early diagnosis of MTC is discussed along with the limitations of cytomorphology alone.

Grading medullary thyroid carcinoma on fine‐needle aspiration cytology specimens with the International Medullary Thyroid Carcinoma Grading System: A cytologic–histologic correlation

“…We performed a validation study of the IMTCGS at our institution that found similar promising results. 8 Of our 87 MTC cases, 18.4% (n = 16) were high grade. These high-grade MTCs had decreased disease-free survival (DFS), DMFS, DSS, and OS compared to low-grade MTCs.…”

“…In our validation study of the IMTCGS on surgical resection material, of the eight high-grade MTCs with increased mitoses (five or greater per 2 mm 2 ), only four showed a concurrent increase in Ki67 PR. 8 On the other hand, only two cases showed an increased Ki67 PR in the absence of an increased mitotic rate. In the current study, we attempted to determine how predictive the mere presence of mitotic figures in MTC cytology might be of tumor grade.…”

Novel prognostic nomogram for predicting recurrence‐free survival in medullary thyroid carcinoma

“…The initial training and discovery cohort was based on 300 patients with MTC from five academic centres (Royal North Shore Hospital [RNSH], Sydney, Australia: n = 58; Institut Gustave Roussy [IGR], Villejuif, France: n = 70; Memorial Sloan Kettering Cancer Center [MSKCC], New York, NY: n = 68; University of Bologna Medical Center [BO], Bologna, Italy: n = 64; and Brigham and Women's Hospital [BWH], Boston, MA: n = 40) which had previously contributed to the IMTCGS study 9 . In addition to k ‐fold validation (described below), as an independent validation cohort we included data from an additional 87 MTC patients from Emory University Midtown Hospital, Atlanta, GA 18 . Although patients from these cohorts were included in prior studies, 7,8,9,18,19 prognostic factors were independently assessed, and survival data updated for this study.…”

“…The predictive model was externally validated using a separate cohort of patients with MTC ( n = 87) from Emory University Midtown Hospital to test the model's generalizability. The clinical and pathological features of this cohort have been previously reported, 18 but were not used in any way for model training. ROC curves for the two cohorts are illustrated in Figure S8.…”

“…The initial training and discovery cohort was based on 300 patients with MTC from five academic 9 In addition to k-fold validation (described below), as an independent validation cohort we included data from an additional 87 MTC patients from Emory University Midtown Hospital, Atlanta, GA. 18 Although patients from these cohorts were included in prior studies, 7,8,9,18,19 prognostic factors were independently assessed, and survival data updated for this study. All cases were previously reviewed at individual participating sites by at least one specialist endocrine pathologist to confirm the diagnosis of MTC as part of the preceding studies.…”