Investigation of the clinical significance of the expression of immunohistochemical biomarkers Enhancer of zeste homolog 2 and Forkhead box M1 in localized prostate cancer tissue: A Greek retrospective study

Abstract

Objective

In recent decades, studies have underscored nuclear proteins and signaling pathways in prostate cancer (PCa) development. Key biomarkers like Enhancer of zeste homolog 2 (EZH2) and Forkhead box M1 (FOXM1) are expressed in both healthy and malignant prostate cells. This study aimed to demonstrate the relationship between pathological characteristics, survival, recurrence, and tissue expression of EZH2 and FOXM1 in high-risk PCa patients.

Methods

PCa tissues were used in a retrospective analysis that spanned from September 2009 to August 2019. Inclusion criteria comprised pathological tumor stage (pT) 3 patients with positive surgical margins or tumor proximity to inked margins within 5 mm. After case selection, tissue slides were stained for EZH2 and FOXM1 antibodies, and Allred scores were calculated. Patients or relatives of deceased patients were contacted for signed agreements and disease follow-ups.

Results

The pT3b, ductal carcinoma component, and moderate EZH2 expression were associated with relapse (odds ratio [OR] 6.21, 95% confidence interval [CI] 1.41–27.27, p=0.016; OR 7.29, 95% CI 1.03–51.43, p=0.046; OR 5.96, 95% CI 1.09–32.48, p=0.039; respectively). The unilateral and bilateral seminal vesicle invasion increased the likelihood of recurrence by 9.98 times and 5.36 times, and the risk of death by around 9.78 times and 10.79 times, respectively. The pT3b was linked to higher death likelihood (OR 7.16, 95% CI 1.38–37.23, p=0.019), while moderate EZH2 expression did not show statistical significance (OR 4.54, 95% CI 0.87–23.60, p=0.072, marginally). Pathological regional lymph node stage (pN) 1 had significantly higher probability of mortality than pN unknown (3.9% vs. 27%, p<0.001). PCa in the neck and apex of the prostate gland increased death risk tenfold.

Conclusion

Sufficient immunoexpression of EZH2, ductal carcinoma component, and neoplastic proliferation in the seminal vesicles, apex and neck of the prostate gland correlates with elevated risks of recurrence and mortality. Clinicians should use these criteria for appropriate patient referrals, and a multicenter trial could provide accurate classifications.