An Evaluation of the Immunohistochemical Expression of Mismatch Repair Proteins (MSH2, MSH6, MLH1, and PMS2) in Prostate Adenocarcinoma
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Updated: Aug 30, 2025

Quantitation of Protein Expression and Co-localization Using Multiplexed Immuno-histochemical Staining and Multispectral Imaging
Published on: April 8, 2016
Saira Javeed1, Anila Chughtai1, Ghazi Zafar1
1Histopathology, Chughtai Institute of Pathology, Lahore, PAK.
Abstract:
Background and objective Mismatch repair (MMR) proteins are an integral part of the cell cycle, and they play an important role in the genomic stability of the microsatellite complex. Microsatellite instability (MSI) is associated with Lynch and multi-tumor syndromes. Identifying patients with Lynch syndrome is essential for screening, early detection, and surveillance of other Lynch syndrome-associated tumors. The role of MMR deficiency is well known in colorectal and endometrial adenocarcinoma. However, the role of MMR deficiency in prostatic adenocarcinoma is a matter of controversy. A few studies have been published to analyze the association between MMR deficiency and prostatic adenocarcinoma. In this study, we used immunohistochemistry to look into the expression of four MMR proteins in prostatic adenocarcinoma: MSH2, MSH6, MLH1, and PMS2. Methodology This was a cross-sectional descriptive study involving 74 cases of acinar prostatic adenocarcinoma, diagnosed with hematoxylin & eosin (H&E), over a period of six months between December 2021 and May 2022 at the Chughtai Institute of Pathology in Lahore, Pakistan. We performed the immunohistochemical (IHC) analysis and interpretation of four antibodies, i.e., MSH2, MSH6, MLH1, and PMS2. Results In our study, the age of the patients ranged from 50 to 98 years, with a mean age of 67.99 ± 9.59 years. The specimens were collected through transurethral resection of the prostate (TURP), transurethral vaporization of the prostate (TVP), core biopsy, and radical prostatectomy. Isolated loss of each MSH2 and PMS2 was noted in nine cases (12.20%) and MSH6 in two cases (2.70%). There was no loss noted for MLH1. Furthermore, simultaneous loss of MSH2/MSH6 was observed in one case (1.35%). Conclusion Our study findings revealed a low frequency of IHC expression of MMR proteins, especially the concurrent loss of paired MMR proteins. However, prostatic adenocarcinoma is associated with the isolated loss of MMR proteins. Thus, the present study does not warrant reflex testing/screening in every case of prostatic adenocarcinoma, because of its low frequency, which is probably suggestive of its sporadic pattern.
Insights
Mismatch repair (MMR) protein deficiency is uncommon in prostatic adenocarcinoma, with isolated loss of MMR proteins observed. This low frequency suggests a sporadic pattern, not warranting routine screening for MMR deficiency in all prostate cancer cases.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Mismatch repair (MMR) proteins are crucial for genomic stability and microsatellite integrity.
- MMR deficiency is linked to Lynch syndrome and various cancers, including colorectal and endometrial adenocarcinoma.
- The role of MMR deficiency in prostatic adenocarcinoma remains controversial and requires further investigation.
Purpose of the Study:
- To investigate the expression of four key MMR proteins (MSH2, MSH6, MLH1, and PMS2) in prostatic adenocarcinoma using immunohistochemistry.
- To determine the frequency and pattern of MMR deficiency in a cohort of prostate adenocarcinoma cases.
Main Methods:
- A cross-sectional descriptive study was conducted on 74 cases of acinar prostatic adenocarcinoma.
- Immunohistochemistry (IHC) was employed to analyze the expression of MSH2, MSH6, MLH1, and PMS2 proteins.
- Specimens were obtained from various procedures including TURP, TVP, core biopsy, and radical prostatectomy.
Main Results:
- The study observed a low frequency of MMR protein deficiency in prostatic adenocarcinoma.
- Isolated loss of MSH2 and PMS2 was noted in 12.20% of cases, and MSH6 loss in 2.70%.
- No loss of MLH1 was detected, and simultaneous loss of MSH2/MSH6 occurred in only 1.35% of cases.
Conclusions:
- Prostatic adenocarcinoma exhibits a low frequency of MMR protein deficiency, particularly concurrent loss of paired proteins.
- Isolated loss of MMR proteins is associated with prostatic adenocarcinoma, suggesting a predominantly sporadic pattern.
- The findings do not support routine reflex testing for MMR deficiency in all prostate adenocarcinoma cases due to its low incidence.

