Evaluation of CD44 Expression in Prostatic Adenocarcinoma: An Institutional Study

Prostate adenocarcinoma is the second-most common cause of cancer. Globally, many cancer-related deaths among men were noted due to prostate adenocarcinoma. CD44 plays a key role in mediating cell-to-cell and cell-to-matrix interaction, which further helps to maintain the integrity of tissue and also inhibits tumor metastasis.

Cross-sectional study was done on chips from transurethral resections of the prostate (TURP) and prostatic core biopsy specimens. All specimens with clinically diagnosed and histopathologically confirmed prostatic adenocarcinoma were included in the study. Prostatic intraepithelial neoplasia (PIN), recurrent cases, and patients who had undergone radiotherapy/ chemotherapy prior to biopsy were excluded from the study. The sample size for the current study was 57 with an 8% prevalence value, 95% confidence interval, and 8% absolute error. Immunoreaction to CD44 antibody is membranous and was evaluated by calculating positively stained cell percentage and staining intensity. These two parameters were added to obtain a final score; a score of 0-3 was considered as negative, and a score of 4-6 was regarded as positive.

A statistically significant difference was only found between Gleason grade (p<0.001), clinical staging (p<0.002), nodal metastasis (p<0.015), and distant metastasis (p<0.020) with CD44 positive expression. The rest of the parameters like PSA (p=0.642) and age (p=0.051) did not correlate with CD44-positive expression. Out of 29 cases with positive CD44 expression, 100% positivity was seen in Gleason's grades 1, 2, and 3. This indicates that CD44 expression showed lesser positivity in poorly differentiated carcinoma. CD44 positivity was seen in 83.3% in the T2 stage. An inverse relationship between tumor staging and CD44 expression was observed with positive CD44 expression in lower tumor staging which implies loss of CD44 expression was associated with greater tumor aggressiveness. Lymph node metastasis cases showed more negative CD44 expression (59.5%) and the same was noted in patients without distant metastasis, that is in 61% of the subjects.  Conclusion: Cells tend to lose the ability of CD44 expression as they progress from well-differentiated adenocarcinoma to poorly differentiated adenocarcinoma. CD44 expression suggests that the tumor is in a well-differentiated and gland-forming state as compared to Gleason's grade. Loss of CD44 expression suggests tumor aggressiveness. Thus, the upregulation of CD44 expression can be considered as a potential target for targeted therapy. As many targeted and gene therapies are in clinical trials, large-scale multicentered studies are needed for a better understanding of the clinical course of the disease.