title: Relationship between MLH-1, MSH-2, PMS-2,MSH-6 expression and clinicopathological features in colorectal cancer.
abstract: Colorectal cancers are the third most common in both sexes and they are the second most common cause of cancer-related death. 12-15% of colorectal cancers develop through microsatellite instability (the hereditary mutation in at least one of DNA mismatch repair genes) pathway and they are 2-5% hereditary. In this study, we investigated the correlation between the clinicopathological features themselves and also the correlation between them and the immunohistochemical MLH-1, MSH-2, PMS-2, MSH-6 expressions in a total of 186 resection materials with colorectal adenocarcinoma between 2008 and 2012. All the cases were retrospectively evaluated in terms of age, sex, localization, size, accompanying polyp, multiple tumor, arising from polyp, differentiation, mucinous differentiation, pathological tumor stage, lymphovascular and perineural invasion, lymphocyte amount in the tumor microenvironment, surgical border and lymph node metastasis. We prepared multiple tissue blocks which had 4-millimeter tumor. Immunohistochemically, MLH-1, MSH-2, PMS-2, MSH-6 primary antibodies were studied. Statistically, "Kruskal-Wallis" ve "Pearson's chi-squared" tests were used. We found a positive correlation between loss of MLH-1 and PMS-2 expressions and the right-colon location, poor and mucinous differentiation and dense lymphocytic infiltration. In addition, loss of MSH-2 and MSH-6 expressions was correlated with the right-colon location, poor and mucinous differentiation. We found a meaningful relationship between immunohistochemical markers and clinicopathological features usually observed in tumors with microsatellite instability. This finding may arouse suspicion for MSI. However, the findings in our study must be supported with studies conducted in large series including molecular methods.
authors.affiliation: Department of Pathology, Izmir Bozyaka Training and Research Hospital Izmir, Turkey.
authors.forename: Birgül
authors.initials: B
authors.lastname: Karahan
authors.affiliation: Department of Pathology, Izmir Bozyaka Training and Research Hospital Izmir, Turkey.
authors.forename: Asuman
authors.initials: A
authors.lastname: Argon
authors.affiliation: Department of General Surgery, Izmir Bozyaka Training and Research Hospital Izmir, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Yıldırım
authors.affiliation: Department of Pathology, Izmir Bozyaka Training and Research Hospital Izmir, Turkey.
authors.forename: Enver
authors.initials: E
authors.lastname: Vardar
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis*; D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000556:secondary / Q000601:surgery; D000251:Adenosine Triphosphatases / Q000032:analysis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002454:Cell Differentiation; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D045643:DNA Repair Enzymes / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D047368:Tumor Burden
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes
keywords: MLH-1; MSH-2; MSH-6; Microsatellite instability; PMS-2; colorectal cancer