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http://purl.uniprot.org/citations/28651545http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28651545http://www.w3.org/2000/01/rdf-schema#comment"

Background

Microsatellite instability (MSI) operates as the second major pathway in the colorectal carcinogenesis. Although genetic testing remains the gold standard for the detection of MSI, the College of American Pathologists (CAP) recommends an initial immunohistochemical workup with a four-antibody panel (MLH1, PMS2, MSH2, and MSH6) to screen for a defective mismatch repair system. An increased trend towards young age colorectal carcinoma (CRC) has been noticed in our population over recent years; however, neither screening for MSI by immunohistochemistry (IHC)/genetic testing was done nor were its morphological features studied. We aimed to determine the frequency of mismatch repair deficiency (dMMR) by loss of IHC expression of the aforementioned enzymes in CRC patients and its correlatation with clinicopathologic parameters.

Methods

This was a retrospective study conducted at Liaquat National Hospital, Karachi, between 2012 and 2015. A total of 100 cases of CRC were included in the study that underwent surgical resection. IHC stains using antibodies MLH1, PMS2, MSH2, and MSH6 were performed by DAKO EnVision method on representative tissue blocks. The results were interpreted by senior histopathologists and correlated with clinico-pathological parameters.

Results

A total of 100 cases of CRC were studied that included 51 males and 49 females. Thirty-four percent (n = 34) of the patients showed loss of IHC staining for MMR markers. Combined loss of expression for MLH1/PMS2 were observed in 16% (n = 16) of the cases. Loss of MSH2/MSH6 were seen in 6% (n = 6) of the cases. Loss of expression for all markers were noted in 7% (n = 7) of the cases. There were 5% (n = 5) of the cases that showed isolated loss of MLH1 only. The tumors with dMMR status were significantly associated with right-sided location (p = 0.013), exhibited intra-tumoral lymphocytosis (p = 0.007), and lymphovascular invasion (p = 0.043). No significant association was seen with gender, age, tumor stage, grade, or other morphological features.

Conclusion

The frequency of mismatch repair deficiency in CRC patients was found to be 34% in Pakistani population which warrants further genetic testing to exclude Lynch syndrome. Moreover, right-sided location and intra-tumoral lymphocyte count may be used to identify patients who may need further workup."xsd:string
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http://purl.uniprot.org/citations/28651545http://purl.uniprot.org/core/author"Ali R."xsd:string
http://purl.uniprot.org/citations/28651545http://purl.uniprot.org/core/author"Khan M."xsd:string
http://purl.uniprot.org/citations/28651545http://purl.uniprot.org/core/author"Faridi N."xsd:string
http://purl.uniprot.org/citations/28651545http://purl.uniprot.org/core/author"Hashmi A.A."xsd:string
http://purl.uniprot.org/citations/28651545http://purl.uniprot.org/core/author"Hussain Z.F."xsd:string
http://purl.uniprot.org/citations/28651545http://purl.uniprot.org/core/author"Bakar S.M.A."xsd:string
http://purl.uniprot.org/citations/28651545http://purl.uniprot.org/core/author"Edhi M.M."xsd:string
http://purl.uniprot.org/citations/28651545http://purl.uniprot.org/core/author"Khan E.Y."xsd:string
http://purl.uniprot.org/citations/28651545http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/28651545http://purl.uniprot.org/core/name"World J Surg Oncol"xsd:string
http://purl.uniprot.org/citations/28651545http://purl.uniprot.org/core/pages"116"xsd:string
http://purl.uniprot.org/citations/28651545http://purl.uniprot.org/core/title"Mismatch repair deficiency screening in colorectal carcinoma by a four-antibody immunohistochemical panel in Pakistani population and its correlation with histopathological parameters."xsd:string
http://purl.uniprot.org/citations/28651545http://purl.uniprot.org/core/volume"15"xsd:string
http://purl.uniprot.org/citations/28651545http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/28651545
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