Validation of the International Medullary Thyroid Carcinoma Grading System in a Multicenter Cohort: Digital Image Analysis-Based Evaluation of Ki-67 Cutoffs and Assessment Methods
Year: 2026
Type: article
Abstract: Although the International Medullary Thyroid Carcinoma Grading System (IMTCGS) was proposed to standardize the histologic grading of medullary thyroid carcinoma (MTC), the validity of its 5% Ki-67 index cutoff and the optimal assessment method remain to be fully established. This multicenter study aimed to validate the Ki-67 index component of the IMTCGS in a Korean cohort using digital image analysis (DIA) and to determine the most clinically relevant evaluation method. We retrospectively analyzed 187 surgically resected MTC cases across 16 institutions. Ki-67 indices were evaluated via DIA using two approaches: the hotspot method (highest proliferative area) and the average method (across three representative regions). Prognostic values of various Ki-67 cutoffs (5%, 3%, and ROC curve-derived thresholds) were evaluated independently and within the IMTCGS framework. IMTCGS high-grade status incorporating the 5% hotspot Ki-67 index emerged as an independent prognostic factor for recurrence-free survival (RFS), along with male sex, elevated postoperative serum calcitonin levels, and pN1b status. IMTCGS grading using the 5% average Ki-67 index failed to retain independent significance. While the composite high-grade IMTCGS classification remained an independent predictor of RFS in multivariate analysis, none of its constituent components (tumor necrosis, mitotic count, or Ki-67 index) retained independent prognostic significance when evaluated separately. This multicenter study validates the prognostic utility of the IMTCGS in Korean MTC patients. DIA-based hotspot Ki-67 assessment provides superior prognostic stratification compared to the average method, supporting its preference for routine clinical IMTCGS implementation.
Source: Endocrine Pathology
Institutions: Yonsei University, Severance Hospital, Gangnam Severance Hospital, Kyungpook National University Medical Center, The Catholic University of Korea Seoul St. Mary's Hospital, Chungnam National University Hospital, Pusan National University Yangsan Hospital, Ajou University, Inje University Busan Paik Hospital, Seoul National University, Seoul National University Hospital, Keimyung University Dongsan Hospital, Yeungnam University College, Yeungnam University, Korea University Anam Hospital, Catholic Kwandong University International St. Mary's Hospital, Soonchunhyang University, Soonchunhyang University Hospital Seoul, Inha University, Inha University Hospital, Seoul National University Bundang Hospital
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,190
OpenAlex ID: W7225770982