Pathological features of colorectal carcinomas in MYH-associated polyposis

Abstract

Aims: MYH is a DNA glycosylase in the base excision repair pathway. Germ-line biallelic mutations in the MYH gene are associated with the development of multiple colorectal adenomas and colorectal carcinoma (CRC). A slightly increased risk of CRC is suggested in monoallelic MYH mutation carriers. The aim was to characterize the histopathological features of carcinomas from biallelics and monoallelics.

Methods and results: Clinicopathological features of 57 colorectal carcinomas from 50 patients identified in familial CRC registries were recorded. These included 16 cancers from 14 MYH biallelics; 25 cancers from 22 MYH monoallelics; and 16 cancers from 14 controls. Carcinomas in biallelics demonstrated tubular, papillary or cribriform patterns as the predominant histological subtype, and main histological groups differed according to mutation status (P = 0.0053). All biallelic cancers were low grade, with high-grade tumours more common in monoallelics and controls (P = 0.002). Synchronous polyps were observed in 75% of biallelics, 33% of monoallelics and 43% of controls (P = 0.035). Serrated carcinoma was the predominant type in 12% (3/25) of the monoallelics but in none of the biallelics or controls. MYH immunohistochemistry failed to distinguish between groups.

Conclusions: Neither pathological features nor immunohistochemistry could predict the MYH mutation status of CRCs in this study.

Figure 1

Serrated carcinoma from a heterozygote. A, The carcinoma has a serrated growth pattern with eosinophilic cytoplasm (H&E). B, Detail of (A) showing vesicular nuclei with chromatin condensation around the nuclear envelope (H&E).

Figure 2

MYH immunohistochemistry showing a similar pattern of granular cytoplasmic reactivity in malignant and benign epithelium from biallelics (A = tumour, B = normal), heterozygotes (C = tumour, D = normal) and controls (E = tumour, F = normal).