Immunohistochemical Expression of MLH1 and MSH2 in Prostate Cancer and Its Implications

Abstract

Background: Prostate cancer is a complex disease characterized by the uncontrolled growth of cells in the prostate. DNA mismatch repair (MMR) proteins, such as MutS homolog 2 (MSH2) and MutL protein homolog 1 (MLH1), play a crucial role in correcting errors in DNA replication that can lead to cancer. Loss of these proteins can result in genetic changes that contribute to the development of cancer. This study aimed to assess the expression of MLH1 and MSH2 in prostate cancer.

Methods: The study was retrospective and involved the analysis of 40 formalin-fixed paraffin-embedded tissue blocks, including 20 blocks from malignant invasive prostate cancer and 20 from benign prostatic hyperplasia (BPH) tissues. Immunohistochemical analysis was conducted using the Avidin-biotin immuno-peroxidase method to detect MLH1 and MSH2 expression. The expression levels were evaluated using a semi-quantitative method, which involved grading the intensity of staining and the percentage of stained cells per field. The stained sections were examined under a LEICA research microscope (LEICA DM750, Switzerland) equipped with a digital camera (LEICA ICC50).

Results: Nuclear staining of MLH1 was observed, with a mean positivity rate (MPR) of 6.4% in BPH cases and 29.7% in prostate cancer cases, where only 50% of cancer cells showed moderate significant expression. Nuclear staining of MSH2 was also detected, with a MPR of 7.6% in BPH cases and 77.4% in prostate cancer cases, where 60% of cancer cells showed significant marked expression. Statistically, MLH1 and MSH2 expression were significantly higher in PC compared to BPH (P<0.05), and MSH2 loss was higher compared to MLH1.

Conclusion: In conclusion, this study revealed low frequency of MLH1 immunohistochemical expression in BPH and prostate cancer. The loss of mismatch repair proteins in prostate cancer suggests a role in DNA repair processes and potential resistance to chemotherapeutic medications. As a result, defect in mismatch repair may accelerate prostate cancer development. Determining the immunohistochemical expression of the DNA mismatch repair (MMR) proteinscan predict tumor behavior, serve as diagnostic markers and guide treatment decisions.