Discussion

The present study aimed to evaluate the clinicopathological profile of prostate adenocarcinoma and BPH, while assessing the immunohistochemical expression of p53 and Ki67 in these lesions and correlating them with tumor grade. Given the heterogeneous biological behavior of prostate adenocarcinoma and the limitations of traditional prognostic parameters, markers such as p53 and Ki67 have garnered interest as potential adjuncts for risk stratification.

In the present study, patients with prostate adenocarcinoma presented at a higher mean age (71.5 years) compared to those with BPH (69 years), with the majority (76%) aged 70 years or older. This finding aligns with that presented in the established literature, including studies by Verma et al. and Bhat et al., which identify advancing age as a predominant non-modifiable risk factor for prostatic malignancy [12,13]. The notable age overlap between patients with BPH and carcinoma observed here underscores the diagnostic challenges in elderly populations and reinforces the necessity of histopathological and immunohistochemical evaluation for accurate differentiation.

Serum PSA levels in adenocarcinoma cases exhibited a wide range (10.3-96.4 ng/mL) with no statistically significant association with Gleason grade groups. This observation supports the growing consensus that PSA alone is an unreliable predictor of tumor aggressiveness. Similar findings were reported by Verma et al., Bhat et al., and Gangwar et al., who noted wide PSA variability across grades and emphasized that high-grade tumors may lose proportional PSA production, leading to disproportionately lower serum levels despite aggressive behavior [12-14]. Consequently, PSA should be interpreted alongside histopathological parameters rather than in isolation.

Histologically, Gleason score 7 was most frequent (48%), with a predominance of the prognostically unfavorable 4+3 pattern over 3+4. High-grade tumors (Gleason score 8-10) constituted 48% of cases, and no well-differentiated tumors were identified. This distribution reflects a substantial burden of advanced disease at presentation, consistent with Indian studies by Verma et al., Bhat et al., Gangwar et al., and Rajeswari et al., and highlights the gaps in early detection practices [12-15].

p53 immunoexpression was observed in 96% of adenocarcinoma cases, with 76% showing strong (3+) positivity. However, no significant association was found between p53 expression and Gleason grade. Moreover, p53 expression did not significantly differ between adenocarcinoma and BPH, limiting its diagnostic utility. These findings concur with those of Thompson et al., Verma et al., and Bhat et al., who concluded that p53 accumulation may reflect genomic instability rather than malignant transformation specifically, and that its mutations are infrequent in primary prostate adenocarcinoma, being more common in the advanced disease [11-13].

In contrast, Ki-67 expression demonstrated significant prognostic relevance. A statistically significant positive correlation was observed between Ki-67 labeling index and Gleason grade group (p=0.047), with higher-grade tumors exhibiting increased proliferative activity. Furthermore, Ki-67 expression was markedly higher in adenocarcinoma compared to BPH (p=0.0001), supporting its diagnostic value in distinguishing malignant from benign lesions. These findings align with those of studies by Gangwar et al., Rajeswari et al., and Muñoz et al., which identified Ki-67 as a reliable indicator of tumor proliferation and aggressiveness [14-16].

Limitations

The present study is limited by its single-center design, small cohort size, and the use of a conventional (old) immunohistochemical method for evaluating p53 expression, which may affect the generalizability of the findings. Furthermore, analyses of clinicopathological subgroups were based on even smaller subcohorts, limiting statistical power and the precision of subgroup comparisons. The cross-sectional design precluded evaluation of long-term clinical outcomes, including recurrence, metastasis, and survival. In addition, molecular analysis of TP53 mutations was not performed, limiting the correlation between p53 protein expression and underlying genetic alterations. Interobserver variability in immunohistochemical interpretation was also not assessed.