Diagnosis of hereditary non‐polyposis colorectal cancer

Abstract

The term hereditary non-polyposis colorectal cancer (HNPCC) was introduced initially to encompass autosomal dominant syndromes predisposing to colorectal cancer other than the polyposes. The term is a poor descriptor and is often applied to families on the basis of inadequate information. It is suggested that 'hereditary mismatch repair deficiency syndrome' (HMRDS) should replace the term HNPCC for describing the specific autosomal dominant condition which predisposes to cancer displaying the mutator phenotype. Population-based studies have shown that HMRDS probably accounts for no more than 2% of bowel cancer. A working diagnosis of HMRDS can be made on the basis of clinical, pathological and molecular characteristics. The histopathologist has an important role to play in the recognition and diagnosis of HMRDS. The characteristic morphology of colorectal cancer in HMRDS is reviewed and the diagnostic utility of 'field changes' and adenomas is discussed critically.

Pancreatic Mucinous Noncystic (Colloid) Carcinomas and Intraductal Papillary Mucinous Carcinomas Are Usually Microsatellite Stable

“…They have been found to cause the HNPCC syndrome but have also been detected in sporadic carcinomas (14,21). Frequently, the MSI carcinomas are of a special histological type, such as medullary carcinomas (15) or, more often, mucinous carcinomas (22). The tissue of the latter carcinomas is composed of Ͼ50% mucin-producing tumor cells and mucus extravasation.…”

Effect of statin therapy on colorectal cancer

“…Alternate preventative strategies have included chemoprevention, which involves the long-term use of a variety of oral agents that can delay, prevent, or even reverse the development of adenomas in the large bowel, and interferes with the multistep progression from adenoma to carcinoma. Chemoprevention is of particular importance to individuals with a hereditary predisposition to colorectal neoplasia6 7 and to those who are especially susceptible to the environmental triggers of CRC.…”

ClassifyingMLH1andMSH2variants using bioinformatic prediction, splicing assays, segregation, and tumor characteristics

“…Identified mutations in the MMR genes MLH1 (MIM# 120436) and MSH2 (MIM# 609309) account for approximately 90% of Lynch syndrome families with detectable mutations, MSH6 (MIM# 600678) for up to 10%, and PMS2 (MIM# 600259) only very occasionally (Hampel, et al, 2005; Viel, et al, 1998; Wang, et al, 1999). Although Lynch syndrome families often exhibit a clinical phenotype of multiple cases of early onset colorectal and endometrial cancers across several generations (Jass, 1998; Lynch, et al, 1998), a more definitive diagnosis can be readily made on two important molecular pathological features of the tumour. Defects in MMR lead to tumour DNA microsatellite instability (MSI), detected in the laboratory as numerous insertion or deletion mutations in short repetitive sequence elements.…”