Diagnosis and management of hereditary colorectal cancer syndromes: Lynch syndrome as a model

Lynch, Henry T.; Lynch, Jane F.; Attard, Thomas

doi:10.1503/cmaj.071574

Cited by 61 publications

(72 citation statements)

References 40 publications

(37 reference statements)

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“…Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) accounts for approximately 2-5% of colorectal cancers [Hampel et al, 2008;Lynch et al, 2009]. The patients are exposed in addition to colorectal cancer to some extracolonic cancers (endometrium, stomach, ovary, kidney, urinary tract, biliary tract, small intestine, brain, and skin tumors).…”

Section: Introductionmentioning

confidence: 99%

Classification of mismatch repair gene missense variants with PON-MMR

Ali¹,

Olatubosun²,

Vihinen

2012

Hum. Mutat.

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Section: Introductionmentioning

confidence: 99%

Classification of mismatch repair gene missense variants with PON-MMR

Ali¹,

Olatubosun²,

Vihinen

2012

Hum. Mutat.

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“…16,22,[29][30][31][32] The FCCTX tumor spectrum is predominated by colorectal cancer and does, in contrast to Lynch syndrome, not show any increased risk of extracolonic cancers. 16,33,34 Colorectal cancers linked to FCCTX are left sided in 70% of the cases. Synchronous as well as metachronous adenomas are frequent with a high adenoma/carcinoma ratio that may suggest a slower adenomacarcinoma progression rate than in Lynch syndrome.…”

mentioning

confidence: 99%

“…Synchronous as well as metachronous adenomas are frequent with a high adenoma/carcinoma ratio that may suggest a slower adenomacarcinoma progression rate than in Lynch syndrome. 16,21,31,33,[35][36][37][38][39] Whereas colorectal cancers linked to Lynch syndrome are characterized by poorly differentiated tumors, mucinous differentiation, an expanding growth pattern, and abundant lymphocytic reactions (including tumor-infiltrating lymphocytes, peritumoral lymphocytes, and Crohn-like reactions), FCCTX tumors typically show a more 'sporadic-like' phenotype with medium high differentiation, glandular and infiltrative growth patterns, and frequent dirty necrosis ( Figure 2). 37,38 The lack of distinct histopathologic features makes identification of FCCTX-associated colorectal cancer challenging from a pathologist's perspective and underscores the importance of obtaining a family history of cancer.…”

mentioning

confidence: 99%

Familial colorectal cancer type X: genetic profiles and phenotypic features

Dominguez‐Valentin

Therkildsen²,

Silva³

et al. 2015

Modern Pathology

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Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) syndrome with the aim to delineate tumor characteristics that may contribute to refined diagnostics and optimized tumor prevention.

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“…Affected individuals have more synchronous and metachronous cancers than sporadic CRC, and these patients are also more likely to have right-sided tumours. 15,16 In this respect, our finding that 70% of our young patients with CRC and all those with MMR protein deficiency, which is suggestive of Lynch syndrome, had left-sided cancers is surprising. Although this finding may be owing to our small sample size, it may warrant further investigation in this population.…”

Section: Discussionmentioning

confidence: 78%

“…It is generally believed that HNPCC or Lynch syndrome accounts for 2%-5% of all cases of CRCs, 15 but it is fair to say that the true prevalence is unknown, and current estimates of the disease may be an underestimate owing in part to the diagnostic criteria.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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Background:We investigated the prevalence of Lynch syndrome as a hereditary cause of colon cancer in the young Jamaican colorectal cancer (CRC) population. Methods:We identified patients aged 40 years or younger in whom primary CRC was diagnosed at the University Hospital of the West Indies from January 2004 to December 2008. We reviewed the medical records and hematoxylin and eosin (H&E)-stained histopathology slides. Tumour blocks were tested for microsatellite instability (MSI). Patients with MSI-high phenotype (MSI-H) tumours had genetic counselling, after which genomic DNA was extracted from peripheral blood to test for MLH1 and MSH2 germline mutations. Patients also had pedigree mapping. Results:There were 25 patients with CRC aged 40 years or younger with no history of hereditary colon cancer syndrome. The patients' mean age was 33 (range 21-40) years. Histopathologic review confirmed CRC in all patients; 8 of 25 (32%) showed morphologic features suggestive of MSI. We detected MSI-H in 5 of 23 (22%) tumour blocks tested. Review with H&E staining correctly identified 80% of cases positive for MSI-H. The false-positive rate and positive predictive value on H&E review was 50%. The negative predictive value of histomorphologic H&E review was 94%. Three patients were available for and had mutational analysis of DNA mismatch repair genes; 2 were positive for mutations in keeping with Lynch syndrome and 1 had MLH1 alterations of uncertain significance. All 3 met the Amsterdam criteria for hereditary nonpolyposis CRC. Conclusion:Thirteen percent of the population had mutations in keeping with Lynch syndrome. This prevalence is similar to that reported for white populations.Contexte : Nous avons analysé la prévalence du syndrome de Lynch comme cause héréditaire du cancer du côlon dans la population jamaïcaine jeune touchée par le cancer colorectal (CCR). Méthodes Conclusion :Treize pour cent de la population présentaient des mutations concordant avec un syndrome de Lynch. Cette prévalence ressemble à celle que l'on observe dans les populations de race blanche.

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Diagnosis and management of hereditary colorectal cancer syndromes: Lynch syndrome as a model

Cited by 61 publications

References 40 publications

Classification of mismatch repair gene missense variants with PON-MMR

Classification of mismatch repair gene missense variants with PON-MMR

Familial colorectal cancer type X: genetic profiles and phenotypic features

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

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