Systematic Immunohistochemistry Screening for Lynch Syndrome in Early Age-of-Onset Colorectal Cancer Patients Undergoing Surgical Resection

Steinhagen, Emily; Shia, Jinru; Markowitz, Arnold J.; Stadler, Zsofia K.; Salo‐Mullen, Erin; Zheng, Junting; Lee-Kong, Steven A.; Nash, Garrett M.; Offit, Kenneth; Guillem, José G.

doi:10.1016/j.jamcollsurg.2011.10.004

Cited by 29 publications

(15 citation statements)

References 38 publications

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“…In particular, in these two groups, the left colon was more frequently involved (77.1% of cases in group A and 71.4% in group C) (Table 1). Previous studies on young CRC series reported, as well, a predilection for the distal colon ranging from 55 to 80% of cases [4,11,21,23,27,29,31,32],[39,40]. The heterogeneity between these studies, compared to the CRC site in early onset CRC, maybe related to the proportion of LS detected in each study, as LS related CRC mainly occurs in the right colon.…”

Section: Discussionmentioning

confidence: 96%

“…These data are in agreement with those of Jasperson et al [20] which reported a low frequency (6.5%) of MMR germline mutations among young patients without family history suspecting LS and found 73.3% of MMR germline mutations in the cases with Amsterdam Criteria. Other authors reported a highly variable prevalence of MMR gene mutation carriers in early onset CRC, ranging between 4.2% and 17.7% [13], [21], [23], [24], [26][27], [31], [32], [39], but the number of cases without family history was specified in few studies [21,27,31]. If we only consider these studies, we will observe a dramatic decrease in the LS prevalence rate to 3.5%-6.4%, in agreement with our results.…”

Section: Discussionmentioning

confidence: 99%

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Early-onset colorectal cancer patients without family history are “at very low risk” for lynch syndrome

Stigliano¹,

Sanchez-Mete²,

Martayan³

et al. 2014

J Exp Clin Cancer Res

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IntroductionSeveral studies evaluated the prevalence of Lynch Syndrome (LS) in young onset colorectal cancer (CRC) patients and the results were extremely variable (5%-20%). Immunohistochemistry (IHC) for MMR proteins and/or MSI analysis are screening tests that are done, either by themselves or in conjunction, on colon cancer tissue to identify individuals at risk for LS. The primary aim of our study was to evaluate the prevalence of LS in a large series of early-onset CRC without family history compared with those with family history. The secondary aim was to assess the diagnostic accuracy of IHC and MSI analysis as pre-screening tools for LS.MethodsEarly-onset CRC patients (≤ 50 years) were prospectively recruited in the study. IHC and MSI analysis were performed in all the patients. Germ-line mutation analysis (GMA) was carried out in all MMR deficient tumors. A logistic regression model was performed to identify clinical features predictive of MSI-H.Results117 early onset CRC cases were categorized in three groups (A, B, C) according with family history of CRC. IHC and MSI analysis showed MMR deficiency in 6/70 patients (8.6%) of group A, 24/40 patients (60%) of group B and none of group C. GMA showed a deleterious mutation in 19 (47.5%) patients of group B. MSI analysis had a diagnostic accuracy of 95.7% (CI 92.1-99.4) and IHC of 83.8% (CI 77.1-90.4). The logistic regression model revealed that by using a combination of the two features “No Amsterdam Criteria” and ”left sided CRC” to exclude MSI-H, accuracy was 89.7% (84.2-95.2).ConclusionsEarly-onset CRC patients, with left sided CRC and without family history are “at very low risk” for Lynch syndrome. The two simple criteria of family history and CRC site could be used as a pre-screening tool to evaluate whether or not patients should undergo tissue molecular screening. In the few cases of suspected LS (right sided CRC and/or Amsterdam Criteria), a reasonable approach could be to perform MSI analysis first and IHC afterwards only in MSI-H patients.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Early-onset colorectal cancer patients without family history are “at very low risk” for lynch syndrome

Stigliano¹,

Sanchez-Mete²,

Martayan³

et al. 2014

J Exp Clin Cancer Res

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show abstract

“…31,32 Our comparison of detailed family history information with MMR IHC test results indeed suggest that IHC testing may be valuable to prioritize genetic testing for mutation-positive patients who did not report a family history of cancer. Although a recent study reported better sensitivity of routine tumor IHC or MSI analysis for loss of MMR protein expression in colorectal cancer patients for detecting Lynch syndrome than family history, 33 IHC performed best in distinguishing mutation carriers from noncarriers when combined with personal and family history.…”

Section: Early Detection and Diagnosismentioning

confidence: 91%

Improving identification of lynch syndrome patients: A comparison of research data with clinical records

Tan

McGaughran

Ferguson

et al. 2013

Intl Journal of Cancer

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Current evidence suggests poor identification and referral of Lynch syndrome patients. This study evaluated the strategies by which patients with endometrial cancer were referred to genetics services. Data from clinic-based patients with endometrial cancer enrolled through the Australian National Endometrial Cancer population-based research study with detailed family history information were analyzed. The Amsterdam II criteria, the revised Bethesda guidelines, and criteria adapted for this study was assessed using personal/family history information. The percentages of patients referred and who could have been referred to genetics services, and the performance of each criterion for identifying possible mismatch-repair (MMR) gene mutation carriers, based on tumor MMR immunohistochemistry (IHC), were determined. Research data indicated that 236/397(59%) of patients with endometrial cancer had family/personal history of cancer, including 14 (4%) who fulfilled Amsterdam II criteria. Family history information was noted in the hospital records for only 61(15%) patients, including 7/14 (50%) of patients meeting Amsterdam criteria, and always less extensively than that recorded in the research setting. Only 13 patients (two meeting Amsterdam criteria) were referred for genetic assessment. Of 58 patients with tumor MMR protein-IHC loss, the Amsterdam criteria and Bethesda guidelines identified only three and 34% of these possible germline mutation carriers, respectively. Greater sensitivity (60%) was obtained using a single criterion proposed by our study, 2 first-degree or second-degree relatives reporting Lynch cancers. Hospital records indicate poor recognition of family history. Application of research methods show improved identification and may facilitate appropriate referrals of endometrial cancer patients with possible Lynch syndrome.

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“…6,7 This strategy can identify a significant number of Lynch syndrome patients. [8][9][10] A description of genomic sequence and a listing of mutations and single-nucleotide polymorphisms (SNPs) for genes is provided in this document. The entire genomic sequence along with the structural motifs of the genes described in this document can be found at http://www.genome.ucsc.edu.…”

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confidence: 99%

ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis)

Hegde

Ferber

Mao

et al. 2014

Genetics in Medicine

146

105

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Systematic Immunohistochemistry Screening for Lynch Syndrome in Early Age-of-Onset Colorectal Cancer Patients Undergoing Surgical Resection

Cited by 29 publications

References 38 publications

Early-onset colorectal cancer patients without family history are “at very low risk” for lynch syndrome

Early-onset colorectal cancer patients without family history are “at very low risk” for lynch syndrome

Improving identification of lynch syndrome patients: A comparison of research data with clinical records

ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis)

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