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Purpose <p>Prostatic adenocarcinoma with neuroendocrine differentiation (PaNED) is distinct from treatment-related and de-novo neuroendocrine prostate carcinomas, yet remains under-investigated in treatment-naïve patients. This study aimed to evaluate the associations of NED extent, synaptophysin intensity score (SIS), and PD-L1 expression with other histomorphological features and prognosis in treatment-naïve PaNED.</p> Materials and methods <p>Seventeen patients with PaNED diagnosed between 2014 and 2024 were retrospectively analyzed. NED was classified as diffuse (≥ 30%) or focal (&lt; 30%), and SIS was scored as weak (+ 1), moderate (+ 2), or strong (+ 3). PD-L1 expression was assessed using tumor proportion score (TPS, cut-off ≥ 1%) and combined positive score (CPS, cut-off ≥ 10). Clinicopathological data and survival outcomes were evaluated.</p> Results <p>The mean age was 65.2 ± 6.6 years, and 47.1% (<i>n</i> = 8) of the cases were Grade Group 5. Diffuse NED was observed in 70.6% of cases, and strong synaptophysin expression in 35.3%. PD-L1 TPS and CPS positivity were detected in 17.6% and 35.3% of patients, respectively. Neither NED extent nor percentage was significantly associated with PD-L1 expression or prognosis. A moderate negative correlation was found between SIS and PD-L1 CPS (rho = -0.48, <i>p</i> = 0.051). Strong synaptophysin expression was significantly associated with shorter overall survival (<i>p</i> = 0.031).</p> Conclusions <p>In treatment-naïve PaNED, higher SIS was correlated with lower PD-L1 CPS values, and strong synaptophysin expression was associated with poorer survival. Assessment of SIS in morphologically suspected neuroendocrine areas may provide additional prognostic information and help predict the PD-L1 response. Larger studies are required to validate these findings.</p>

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Prognostic significance of neuroendocrine differentiation and PD-L1 expression in treatment-naïve prostate cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月17日

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  • Ilkay Tosun,
  • Onur Sahin,
  • İrem Güvendir Bakkaloğlu,
  • Nurullah Mustafa Şişik,
  • Melike Özçelik

摘要

Purpose

Prostatic adenocarcinoma with neuroendocrine differentiation (PaNED) is distinct from treatment-related and de-novo neuroendocrine prostate carcinomas, yet remains under-investigated in treatment-naïve patients. This study aimed to evaluate the associations of NED extent, synaptophysin intensity score (SIS), and PD-L1 expression with other histomorphological features and prognosis in treatment-naïve PaNED.

Materials and methods

Seventeen patients with PaNED diagnosed between 2014 and 2024 were retrospectively analyzed. NED was classified as diffuse (≥ 30%) or focal (< 30%), and SIS was scored as weak (+ 1), moderate (+ 2), or strong (+ 3). PD-L1 expression was assessed using tumor proportion score (TPS, cut-off ≥ 1%) and combined positive score (CPS, cut-off ≥ 10). Clinicopathological data and survival outcomes were evaluated.

Results

The mean age was 65.2 ± 6.6 years, and 47.1% (n = 8) of the cases were Grade Group 5. Diffuse NED was observed in 70.6% of cases, and strong synaptophysin expression in 35.3%. PD-L1 TPS and CPS positivity were detected in 17.6% and 35.3% of patients, respectively. Neither NED extent nor percentage was significantly associated with PD-L1 expression or prognosis. A moderate negative correlation was found between SIS and PD-L1 CPS (rho = -0.48, p = 0.051). Strong synaptophysin expression was significantly associated with shorter overall survival (p = 0.031).

Conclusions

In treatment-naïve PaNED, higher SIS was correlated with lower PD-L1 CPS values, and strong synaptophysin expression was associated with poorer survival. Assessment of SIS in morphologically suspected neuroendocrine areas may provide additional prognostic information and help predict the PD-L1 response. Larger studies are required to validate these findings.