An Evaluation of the Immunohistochemical Expression of Mismatch Repair Proteins (MSH2, MSH6, MLH1, and PMS2) in

Saira Javeed1, Anila Chughtai1, Ghazi Zafar1

  • 1Histopathology, Chughtai Institute of Pathology, Lahore, PAK.

Cureus
|September 2, 2022
PubMed

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.