Frequency and clinicopathologic features of DNA mismatch repair protein deficiency in colorectal carcinoma in Turkish population: Mismatch repair deficiency in colorectal carcinoma

Fatma Yıldırım; Murat Sezak; Tayfun  Yoldaş; Bülent Karabulut; Başak Doğanavşargil

doi:10.5281/zenodo.11111148

Authors

Fatma Yıldırım Lokman Hekim University, Faculty of Medicine, Department of Pathology, Ankara, Turkey https://orcid.org/0000-0003-3887-702X
Murat Sezak Ege University, Faculty of Medicine, Department of Pathology, İzmir, Turkey https://orcid.org/0000-0002-0457-4832
Tayfun Yoldaş Ege University, Faculty of Medicine, Department of General Surgery, İzmir, Turkey https://orcid.org/0000-0002-1796-7854
Bülent Karabulut Ege University, Faculty of Medicine, Department of Medical Oncology, İzmir, Turkey https://orcid.org/0000-0002-1949-8334
Başak Doğanavşargil Ege University, Faculty of Medicine, Department of Pathology, İzmir, Turkey https://orcid.org/0000-0002-4738-4350

DOI:

https://doi.org/10.5281/zenodo.11111148

Keywords:

Colorectal cancer, microsatellite instability, mismatch repair deficiency, prognosis

Abstract

Objective: Microsatellite instability pathway caused by loss of DNA “Mismatch Repair genes” (MMR) is responsible of Lynch Syndrome-related tumors and 10-15% of sporadic colorectal cancers. Although MSI-test is regarded as the golden standard for detection of “Lynch Syndrome-related tumors”, there are increasing evidence on similar analytic sensitivity of immunohistochemical evaluations.

Methods: We retrospectively evaluated 1,002 colorectal tumors for loss of DNA MMR protein (MLH1, PMS2, MSH2, MSH6) immunohistochemically. The results were correlated with clinicopathological features and high level-microsatellite instability (MSI-H) related histological parameters.

Results: MMR protein expression loss was observed in 9.8% of the cases. MLH1-PMS2 loss (53.2%) was the most common loss followed by MSH2-MSH6 (31.6%), isolated PMS2 loss (12%), and isolated MSH6 loss (2%). MMR deficiency was more frequent under 50 years-old (p<0.0001), in right colon tumors (p<0.0001), poorly differentiated tumors (p<0.0001), tumors with tumor infiltrating lymphocytes (p<0.0001), mucinous component (p=0.001), and medullary component (p<0.0001). Also MMR deficiency was less frequent in tumor with tumor budding (p<0.0001) and dirty necrosis (p<0.0001). The 5 years-survival rate was 55.7%. No significant correlation was found with MMR deficiency and survival.

Conclusions: MMR deficiency was observed in 9.8% of the cases with distinct clinicopathological features. The results were consistent with previous studies. Unlike the literature, we did not find any statistically significant difference between MMR deficiency and prognosis.

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