Immunohistochemical study of endometrial high-grade endometrioid carcinoma with or without a concurrent low-grade component: implications for pathogenetic and survival differences.

Abstract

To compare the clinical and pathogenetic differences between high-grade (HG) endometrioid carcinomas with and without concurrent low-grade (LG) components. The expression of ARID1A, PTEN, p53 and mismatch repair (MMR) proteins in HG endometrioid carcinomas without (n = 19) or with (n = 22) concurrent LG endometrioid carcinomas was studied by immunohistochemistry. Microsatellite instability (MSI) was also tested in 31 cases. The frequencies of ARID1A loss, PTEN loss, MMR deficiency or MSI and aberrant p53 expression were 58%, 37%, 37% and 47% in pure HG tumours, and 77%, 45%, 55% and 32% in HG tumours with concurrent LG components (P = 0.07 for ARID1A; P > 0.1 for other proteins). Pure HG tumours had a higher frequency of the type II phenotype (positive for ARID1A, PTEN and MMR proteins; aberrant p53 expression) than HG tumours with concurrent LG components (21% versus 5%) (P = 0.2). The 5-year overall survival rate was worse for pure HG tumours (61.7%) than for HG tumours with concurrent LG components (93.3%) (P = 0.07). HG endometrioid carcinomas are heterogeneous in pathogenesis: some arise from LG endometrioid carcinomas via the type I pathway, whereas others may arise de novo through either the type I pathway or the type II pathway, and have a different prognosis. Thus, HG endometrioid carcinomas should be subclassified properly and treated accordingly.