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DOI: 10.1055/s-0038-1668894
Systematic immunohistochemistry for microstatellite instability in colorectal cancer specimens. A comprehensive approach for personalized treatment?
Publication History
Publication Date:
13 August 2018 (online)
Background:
At least 10 – 15% of cases with unselected colorectal cancer (CRC) are inherent to the pathway of microstellite instability (MSI). A subset of these pertain to Lynch syndrom as a genetic predisposition for CRC and other extra intestinal tumors following mutations in the MMR genes. Both the hereditary and sporadic forms of MSI cancers require a different therapeutic approach regarding adjuvant therapy. Immunohistochemical (IHC) staining of tumor specimens for MSI using antibodies against the most frequent MMR proteins (MLH1, MSH2, MSH6 and PMS2) represents a cost effective method of investigating MSI in colorectal cancer specimens. A reflex testing, as implemented in the UK according to 2017 guidelines, may be the most efficient approach to select candidates that do not require adjuvant therapy (UICC 2) and also pose an ideal potential for identifying candidates with a genetic predisposition to cancer (Lynch syndrome) and are much more reliable than family history selection using the revised Bethesda criteria.
Methods:
Data from a prospectively maintained database of patients undergoing surgical resection of CRC was reviewed. The findings from IHC staining for MLH1, MSH2, MSH6 and PMS2 were reviewed. Cases with negative IHC stains for MHL1 and PMS2 were further stratified via BRAF mutation analysis.
Results:
Tumor specimens from 138 patients (60 females and 78 males) following resection of CRC were analyzed. Positive revised Bethesda criteria were positive in 7.2% of the cohort. MSI – H was found in 29% of cases. Results of MSI via IHC and BRAF analysis warranted genetic counseling and further work-up for Lynch syndrome in 13.7% of cases.
Conclusion:
Systematic screening of CRC specimens für MSI via IHC can easily and cheaply identify potential candidates for further germline LS-testing. Additionally, this procedure has been implemented as the basis for decision-making in tumor boards in order to assess the rationale for adjuvant therapy in cases with sporadic MSI cancers. Systematic testing should be implemented for all CRCs independent of family history, following the NIVE recommendations in the UK.
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