The prognostic importance of CDX2, SOX2, STAT1 and BRAF V600E expression in microsatellite instable colorectal carcinoma cases

Aim: Although MSI CRCs exhibit different clinical and pathological features from MSS tumors, they are associated with a favorable clinical course. Revealing the histopathological and prognostic marker differences between these two tumor groups improves the clinical approach by enabling us to better recognize these entities. In our study, it was aimed to examine MSI and MSS colon tumors diagnosed in our department clinically and histopathologically, to distinguish between these tumors and to determine the effects of CDX2, BRAF, SOX2 and STAT1 expressions on histopathological parameters and prognosis, which we think may have a pognostic significance. Material and methods: Between 2000 and 2018, 593 colorectal adenocarcinoma cases with resection material in our hospital were examined by tissue microarray method. MSI and MSS tumors were detected by immunohistochemical methods. Histopathological and clinical parameters were examined in both tumor groups, CDX2, BRAF, SOX2 and STAT1 immune markers were evaluated, and differences between groups were determined. Then, the effects of these data on survival were investigated on 353 patients for whom we have prognostic information. Results: MSI was detected in 19.1% of the cases. MSI tumors were associated with increased tumor size, loss of differentiation, right colonic location and mucinous morphology, whereas MSS tumors were associated with increased perineural invasion and distant metastasis as well as early levels of invasion. The cases were compared in the presence of other histopathological findings, based on the main histopathological prognostic parameters, the depth of invasion and lymph node metastasis. In MSS cases, deep invasion level was associated with high TT, PDC, and lymph node metastasis. Lymph node metastasis rates increased in both groups with loss of differentiation, high TT, PDC and LVI levels. When we look at the relationship between immune markers and our findings, BRAF expression was associated with; MSI, right colon localization, increased tumor size and poor differentiation, CDX2 expression was associated with; MSS, left colonic location, good differentiation and decreased PNI; SOX2 expression was associated with poor differentiation and increased TIL, and STAT1 expression was associated with; MSI right colonic location, poor differentiation, early invasion levels, increased TIL, and high TT. Although survival was higher in MSI cases, no significant difference was found between the two groups. Advanced age, surgical margin positivity, tumor perforation, mucinous morphology, loss of differentiation, LVI, venous invasion, PNI, tumor deposit, LN metastasis, TT, PDC, advanced TNM stage were associated with decreased survival, and high peritumoral lymphocyte levels were associated with increased survival. High nuclear expression of CDX2 and STAT1 was associated with increased survival in the MSS group. Conclusion: In our study, differences between MSI and CNS tumors, which develop with different mechanisms and have different clinical reflections, were revealed. MSI tumors were found to be larger in size and poorly differentiated, with more frequent mucinous morphology, but with better prognostic features. Advanced age, positive surgical margins, tumor perforation, mucinous morphology, loss of differentiation, LVI, venous invasion, PNI, tumor deposit, LN metastasis, TT, PDC, advanced TNM stage were found to be poor prognostic factors. CDX2 expression was found to be associated with good prognosis in MSS cases, but if it is to be used as a prognostic marker, it was thought that standardization should be provided in evaluating its expression. It was concluded that BRAF mutation should be investigated in CRCs as it will help in predicting prognosis and treatment response and in choosing effective treatment management. SOX2 expression was found to be associated with increased TIL, and it was thought that it could be used as a marker to predict the success of immunotherapy treatment, and it was determined that more studies are needed to reveal its effect on prognosis and its relationship with clinicopathological parameters. Although it was determined that STAT1 is a prognostic marker, it was thought that immunohistochemical studies on STAT1 should be increased and the evaluation should be standardized, and it was found that it had different effects on prognosis with different pathways. It has also been found that it can guide immunotherapy treatment with increased TIL rates. Key words: Microsatellite instable colorectal carcinoma, CDX2, SOX2, BRAF, STAT1