Clinicopathological Significance of Exosomal Proteins CD9 and CD63 and DNA Mismatch Repair Proteins in Prostate Adenocarcinoma and Benign Hyperplasia.

Kristofs Folkmanis,Vilnis Lietuvietis,Igors Ivanovs,Janis Eglitis,Maris Jakubovskis,Inese Folkmane,Sven Laabs,Valdis Folkmanis,Elizabete Junk,Evelina Merdane,Sergejs Isajevs

doi:10.3390/diagnostics12020287

Abstract

Introduction. Recently, it has been shown that exosomal biomarkers and DNA mismatch repair proteins (MMR) could play an important role in cancer risk stratification and prognosis assessment. The gold standard for prostate carcinoma (PCa) diagnosis is biopsy and histopathological examination. Thus, the complex evaluation of exosomal and MMR proteins could be beneficial for prostate cancer risk stratification and diagnostics. The aim of the current study was to evaluate and compare the expression of exosomal proteins CD9 and CD63 and MMR proteins in the tissue of patients with prostate benign hyperplasia (BPH) and PCa. Methods. The study was retrospective. Altogether, 92 patients with PCa and 20 patients with BPH (control group) were enrolled in the study. Exosomal and MMR protein expression was analyzed by immunohistochemistry (IHC). The follow-up for each PCa patient in our study lasted till disease progression and/or a maximum of 5 years. Results. Low-grade PCa was observed in 56 patients and high-grade PCa in 36 patients. CD63 expression was significantly higher in patients with high-grade PCa compared to those with low-grade PCa. CD9 expression was significantly downregulated in PCa patients compared to the control group. MMR protein expression deficiency was observed in 10 PCa patients. MMR proteins were maintained in all cases of BPH. The study found a negative correlation between MMR protein loss and PCa ISUP grade groups. Progression-free survival (PFS) in patients with MMR deficiency was significantly shorter than in patients with maintained MMR expression. Conclusions. CD9 protein expression was downregulated in PCa, compared to BPH, while CD63 protein expression was upregulated in high-grade PCa but downregulated in low-grade PCa. CD63 protein upregulation, CD9 downregulation, and loss of MMR protein characterized the shorter PFS of high-grade PCa patients. CD9, CD63, and MMR could be the routine immunohistochemical biomarkers for the diagnosis and risk stratification of PCa.

Highlights

It has been shown that exosomal biomarkers and DNA mismatch repair proteins (MMR) could play an important role in cancer risk stratification and prognosis assessment
92 patients with prostate acinar adenocarcinoma undergoing radical prostatectomy (RP) and 20 patients undergoing fine-needle biopsy with histopathologically confirmed benign prostate hyperplasia (BPH) diagnosis in the year 2013–2015 were enrolled in the study
112 patients were enrolled in the study, of which 92 patients were with prostate carcinoma (PCa) and 20 patients were with BPH

Summary

Introduction

It has been shown that exosomal biomarkers and DNA mismatch repair proteins (MMR) could play an important role in cancer risk stratification and prognosis assessment. Different risk classification tools have been developed to distinguish patients with early PCa according to the prognosis, including the D’Amico classification system, the Cancer of the Prostate Risk Assessment score, and the National Comprehensive Cancer Network (NCCN) risk groups classification [1,2,4,5]. These systems recognize a low risk of cancer progression for PCa patients with ISUP grade group ≤ 2. Liquid biopsies, circulating tumor cells, exosomes, and circulating nucleic acids have been developed as minimally invasive assays to monitor PCa patients [1,6,7]

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Results