Low Frequency of Lynch Syndrome Among Young Patients With Non-Familial Colorectal Cancer

Goel, Ajay; Nagasaka, Takeshi; Spiegel, Jennifer L.; Meyer, Richard L.; Lichliter, Warren E.; Boland, C. Richard

doi:10.1016/j.cgh.2010.06.030

Cited by 68 publications

(57 citation statements)

References 20 publications

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“…However, LSs represent 9.2% –21.3% of cases in this subgroup14–21 and this research like other current studies55–57 revealed it is a heterogeneous disease, which includes cases with a high familial component other than LS as well as a substantial proportion of sporadic cases with distal location.…”

Section: Discussionsupporting

confidence: 85%

Prevalence and clinicopathological characteristics of mismatch repair-deficient colorectal carcinoma in early onset cases as compared with late-onset cases: a retrospective cross-sectional study in Northeastern Iran

et al. 2018

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ObjectivesLynch syndrome (LS), a genetically inherited autosomal disorder, increases the incidence of colorectal carcinoma (CRC). We aimed to perform a universal strategy to assess the prevalence and clinicopathological characteristics of early onset CRCs at high risk of LS versus late-onset ones in the Iranian population.SettingA local population-based study from Northeastern Iran.Participants321 consecutive CRCs and pathology specimen screened between 2013 and 2016.Primary and secondary outcome measuresRetrospectively, information regarding the clinical criteria was obtained by interviewing the patients with CRC or, their families. Pathologists tested tumours with immunohistochemistry (IHC) staining of four mismatch repair (MMR) proteins (MLH1, MSH2, MSH6 and PMS2). Tumours with absent IHC staining of MLH1 were tested for BRAF mutations to exclude sporadic CRCs. Prevalence of early onset CRCs at high risk of LS and familial CRC type X were assessed as primary and secondary outcome measures, respectively.ResultsOf 321 CRCs (13/123 (10.57%), early onset vs 21/198 (10.6%) late-onset) were detected to be MMR-deficient (dMMR). Nine early onset cases and 14 late-onset ones with a loss of MLH1 underwent testing for the BRAF mutation, none of the early onset and four (2.02%) late-onset were recognised as sporadic. The difference in the outcome of IHC-analysis between early and late-onset CRCs at high risk of LS was not statistically significant (p=0.34). Majority of the suspected LS tumours from early onset patients had arisen in distal part (8/11 (72.72%) vs 8/14 (57.14%)), all of which were occurred in the rectum or sigmoid.ConclusionClinically, these findings suggest that in case of limitation for BRAF testing, the practitioner in Iran may consider managing early onset dMMR cases like LS until access to BRAF testing becomes available to them, before germline testing to accurately diagnose LS.

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Section: Discussionsupporting

confidence: 85%

Prevalence and clinicopathological characteristics of mismatch repair-deficient colorectal carcinoma in early onset cases as compared with late-onset cases: a retrospective cross-sectional study in Northeastern Iran

et al. 2018

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“…There was a strong nuclear reactivity to both hMSH2 and hMSH6 (92.3% to 100%) in all biopsied areas, which is similar to the findings in developed country populations [14,15]. This may be attributed to the fact that since this is a general community hospital, it accepts all types of patients with colorectal carcinoma, thus eliminating selection bias.…”

Section: Discussionsupporting

confidence: 67%

1114 Status of mismatch repair genes hMSH2 and hMSH6 in colorectal cancer in Saudi patients: an immunohistochemical analysis

Alkhalidi¹,

Kfoury²

2012

Easter Mediterr Health J

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This study aimed to identify the status of 2 major microsatellite instability markers (repair genes hMSH2 and hMSH6) in colorectal cancer cases operated at King Khalid University Hospital, Riyadh, Saudi Arabia between 2007 and 2009. Immunohistochemical study of microsatellite instability was done with antibodies to hMSH2 and hMSH6. A total of 32 blocks were analysed from patients aged 16-83 years (median 56 years); 14 blocks (43.8%) were from resections and 18 (56.2%) were from biopsies. An adenomatous component was present in 4 (12.5%) blocks. The colonic carcinoma, the adenomas and the normal tissue showed strong nuclear reactivity to hMSH2 and hMSH6 in 96.9% of the cases. The rate of loss of expression was 3.1%. The rate of mutation in our sampled population was low and matched the rate reported in the literature from industrialized countries. Further studies are needed to confirm the use of these markers in the diagnosis of colorectal cancer.

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“…Of these 59 patients, most were in the distal colorectum (42/59, 71%), none demonstrated BRAF mutations, and 14/59 (24%) demonstrated KRAS mutations. 24 Our results identified a lower rate of KRAS mutation (4%) in early-onset colorectal carcinoma. The reason for this discrepancy is not entirely clear, although a lower frequency of KRAS mutation was also observed in our control group of carcinomas identified over the age of 40 years.…”

Section: Discussionmentioning

confidence: 48%

“…Goel et al 24 analyzed 75 colorectal carcinomas diagnosed in patients under the age of 50 and identified 59 with proficient mismatch repair. Of these 59 patients, most were in the distal colorectum (42/59, 71%), none demonstrated BRAF mutations, and 14/59 (24%) demonstrated KRAS mutations.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: an adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features

et al. 2012

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Recent literature suggests an increasing incidence of colorectal carcinoma in young patients. We performed a histologic, molecular, and immunophenotypic analysis of patients with sporadic early-onset (r40 years of age) colorectal carcinoma seen at our institution from the years 2000-2010 and compared these tumors to a cohort of consecutively resected colorectal carcinomas seen in patients 440 years of age. A total of 1160 primary colorectal adenocarcinomas were surgically resected for the years 2000 through 2010. Of these, 75 (6%) were diagnoses in patients r40 years of age of which 13 (17%) demonstrated abnormalities in DNA mismatch repair, 4 (5%) were in patients with known germline genetic disorders (two patients with familial adenomatous polyposis, one patient with juvenile polyposis, and one patient with Li-Fraumeni syndrome), and three patients (4%) had long-standing chronic inflammatory bowel disease. The sporadic early-onset colorectal carcinoma group comprised a total of 55 patients (55/1160, 5%) and were compared with a control group comprising 73 consecutively resected colorectal carcinomas with proficient DNA mismatch repair in patients 440 years of age. For the early-onset colorectal carcinoma group, most cases (33/55, 60%) were diagnosed between the age of 35 and 40 years of age. Compared with the control group, the early-onset colorectal carcinoma group was significantly different with respect to tumor location (Po0.007) with 80% (44/55 cases) identified in either the sigmoid colon (24/55, 44%) or rectum (20/55, 36%). Morphologically, early-onset colorectal carcinomas more frequently displayed adverse histologic features compared with the control colorectal carcinoma group such as signet ring cell differentiation (7/55, 13% vs 1/73, 1%, P ¼ 0.021), perineural invasion (16/55, 29% vs 8/73, 11%, P ¼ 0.009) and venous invasion (12/55, 22% vs 4/73, 6%, P ¼ 0.006). A precursor adenomatous lesion was less frequently identified in the early-onset colorectal carcinoma group compared with the control group (19/55, 35% vs 39/73, 53%, P ¼ 0.034). Of the early-onset colorectal carcinomas, only 2/45 cases (4%) demonstrated KRAS mutations compared with 11/73 (15%) of the control group colorectal adenocarcinomas harboring KRAS mutations, although this difference did not reach statistical significance (P ¼ 0.13). BRAF V600E mutations were not identified in the early-onset colorectal carcinoma group. No difference was identified between the two

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Low Frequency of Lynch Syndrome Among Young Patients With Non-Familial Colorectal Cancer

Cited by 68 publications

References 20 publications

Prevalence and clinicopathological characteristics of mismatch repair-deficient colorectal carcinoma in early onset cases as compared with late-onset cases: a retrospective cross-sectional study in Northeastern Iran

Prevalence and clinicopathological characteristics of mismatch repair-deficient colorectal carcinoma in early onset cases as compared with late-onset cases: a retrospective cross-sectional study in Northeastern Iran

1114 Status of mismatch repair genes hMSH2 and hMSH6 in colorectal cancer in Saudi patients: an immunohistochemical analysis

Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: an adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features

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