Identification and Classification of Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome): Adapting Old Concepts to Recent Advancements. Report from the Italian Association for the Study of Hereditary Colorectal Tumors Consensus Group

Abstract

Knowledge about hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome clearly evolved during the last 10 to 15 years much more rapidly than in the past century. Consequently, long-established concepts and attitudes that held for many years should now be changed or updated. With regard to classification, we suggest maintaining the eponym "Lynch syndrome" for families that have a well-documented deficiency of the DNA mismatch repair system, whereas "clinical hereditary nonpolyposis colorectal cancer" should be reserved for those families that meet the Amsterdam criteria but without evidence of mismatch repair impairment. Any family (or individual) meeting one or more of the Bethesda criteria can be considered as suspected HNPCC. For the identification of hereditary colorectal cancer molecular screening or the pedigree analysis show advantages and disadvantages; the ideal would be to combine the two approaches. Diffusion of the microsatellite instability test and of immunohistochemistry in the pathology laboratories might render in the immediate future molecular screening more realistic. Strict endoscopic surveillance of family members at risk (with first colonoscopy at age 20-25 years and then every 2-3 years) is needed only in families with documented alterations of the DNA mismatch repair. To a certain extent, our conclusions were similar to the recently proposed "European guidelines for the clinical management of HNPCC," although we prefer the term "clinical hereditary nonpolyposis colorectal cancer," instead of familial colorectal cancer, for families meeting the Amsterdam criteria but not having evidence of mismatch repair impairment.

Population prevalence of familial cancer and common hereditary cancer syndromes. The 2005 California Health Interview Survey

“…Our family history criteria for hereditary nonpolyposis colorectal cancer (HNPCC) were adapted from the Amsterdam II criteria 11 and revised Bethesda guidelines. 12,13 The revised Bethesda criteria are used to determine which individuals with colon cancer should undergo testing of their tumor for microsatellite instability. An adaptation of these criteria was used to identify family histories that suggested the possible diagnosis of HNPCC.…”

“…We have chosen these thresholds for early-and late-onset cancer based on published guidelines. 4,[11][12][13] …”

“…1). 4,[11][12][13] However, certain criteria could not be applied because the necessary data were not collected. For example, for HBOC, family history of bilateral breast cancer and Ashkenazi Jewish ancestry were not available, and for HNPCC, only family histories of colorectal and endometrial cancers were considered.…”

“…For both syndromes, guidelines are available regarding family history criteria for genetic testing and early cancer detection and prevention interventions. [3][4][5][11][12][13] The family history rules we developed for HBOC and HNPCC were derived from the family history criteria found in these guidelines (Fig. 1).…”

Lynch syndrome in a predominantly Afrocentric population: a clinicopathological and genetic study

“…Identification of supporting MMR mutations in patients who fulfill the original Amsterdam criteria varies among institutions, with rates of 50% and 70% often reported. 23,24 Two of our patients had mutations in keeping with a diagnosis of Lynch syndrome, whereas a third had alterations of uncertain significance. This patient would not be considered to belong to the familial CRC type X (FCC type X), as, although the family met the Amsterdam criteria, there was MMR immunodeficiency.…”