Lynch syndrome

Lynch, H. T., and Smyrk, T. 1996. Hereditary nonpolyposis colorectal cancer (Lynch Syndrome) An updated review. Cancer 78 1149-1167. 

Vasen HFA, Watson P, Mecklin JP, Lynch HT and The International Collaborative Group on HNPCC. New clinical criteria for Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome) proposed by the International Collaborative Group on HNPCC. Gastroenterology 1999 116 1453-6. 

Lynch HT, Lynch J. Lynch syndrome Genetics, natural history, genetic counseling, and prevention. J Clin Oncol 2000 18(Nov 1 suppl) 19s-31s. 

Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004 96 261-268. 

FIGURE 14.22 High and low magnification of an invasive cecal adenocarcinoma from a 46-year-old patient with hereditary nonpolyposis colon cancer syndrome (Lynch syndrome). Neoplastic cell nuclei are completely devoid of MLH2 immunoreactivity, whereas cell nuclei of the surrounding stromal cells stain strongly. Only the complete absence of nuclear staining should be interpreted as a marker of a mismatch repair enzyme defect. 

Hampel H, Frankel WL, Martin E, et al. Feasibility of screening for lynch syndrome among patients with colorectal cancer. J Clin Oncol. 2008 26 5783-5788. 

Endometrial cancer is the most common gynecologic cancer in women with Lynch syndrome, and about 12% of women with the syndrome will develop ovarian cancer. The same types of testing that are performed on endometrial cancer specimens can also be performed on ovarian tumors. Unfortunately, in contrast with the substantial body of knowledge that exists about endometrial cancers developing in affected women, little is known about the ovarian cancers that they develop. For example, we do not know what histologic types of cancers they develop, and there are no histologic criteria... 

As discussed earlier in this chapter, Lynch syndrome or hereditary nonpolyposis colon cancer syndrome (HNPCC) is a cancer predisposition syndrome caused by mutation of a mismatch repair gene. Immunohistochemistry can be used to screen for mutations in... 

Lynch HT, Lanspa S, Smyrk T, et al. Hereditary nonpolyposis colorectal cancer (Lynch syndromes I II). Genetics, pathology, natural history, and cancer control. Part I. Cancer Genet Cytogenet. 1991 53 143-160. 

Lynch HT, Smyrk T. An update on Lynch syndrome. Curr Opin Oncol. 1998 10 349-356. 

Lu KH, Schorge JO, Rodabaugh KJ, et al. Prospective determination of prevalence of Lynch syndrome in young women with endometrial cancer. / Clin Oncol. 2007 25 5158-5164. 

Hampel H, Frankel W, Panescu J, et al. Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res. 2006 66 7810-7817. 

Soliman PT, Broaddus RR, Schmeler KM, et al. Women with synchronous primary cancers of the endometrium and ovary Do they have Lynch syndrome J Clin Oncol. 2005 23 9344-9350. 

B. Application to Digestive Tract Tumors in Lynch Syndrome... 

B. Explanation of the Lynch Syndrome-Associated Tumor Spectrum... 

Lack of polyposis in Lynch syndrome appears like another logical consequence (1) There is no reason that at-risk people should develop more sporadic (RER —) adenomas than the general population (2) They are protected from the development of RER+ adenomas by apoptosis (3) Whenever a RER+ adenoma appears, it is difficult to observe because it degenerates so rapidly into a carcinoma. 

This shift in perspective led us to consider Lynch syndrome to be an inherited predisposition to short-lived foci of RER + cells, which appear when somatic cells lose the wild-type allele of the MMR gene involved, and dis-... 

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