Prognostic implications of synaptophysin, CD56, thyroid transcription factor-1, and Ki-67 in pulmonary high-grade neuroendocrine carcinomas

Abstract

Background

The correlation between the expression of immunohistochemical markers and the clinicopathological characteristics of pulmonary high-grade neuroendocrine carcinomas (HGNEC) and its impact on the clinical outcomes of individuals with HGNEC has not yet been explored.

Methods

This study enrolled patients diagnosed with HGNEC between April 2015 and July 2023. Based on the expression levels of synaptophysin (Syn), the neural cell adhesion molecule (CD56), thyroid transcription factor-1 (TTF-1), and Ki-67, a comprehensive analysis was conducted. This involved a comparison of clinicopathological characteristics, chemosensitivity, overall survival (OS), and progression-free survival (PFS). Furthermore, the study identified prognostic factors associated with patient survival through univariate and multivariate analyses.

Results

Eighty-two patients were analyzed. Significant differences were identified in tumor stage (χ² = 5.473, P = 0.019), lymphatic invasion (χ² = 8.839, P = 0.003), and distant metastasis (χ² = 5.473, P = 0.019), respectively, between the CD56 positive and negative groups. A significant difference in lymphatic invasion was observed (χ² = 9.949, P = 0.002) between the CD56 positive and negative groups. A significant difference in vascular invasion was observed (χ² = 5.106, P = 0.024) between the low and high Ki-67 groups. Compared to the Syn negative group, the Syn positive group had significantly shorter PFS (P = 0.006). Compared to the Syn negative group, the Syn positive group had significantly shorter OS (P = 0.004). The CD56 positive group also had significantly shorter OS than the CD56 negative group (P = 0.027). Univariate analysis revealed that tumor stage and Syn expression were associated with OS and PFS. Lymphatic invasion and CD56 expression were associated with OS. Multivariate analysis revealed that tumor stage was the strongest predictor of poor prognosis for OS (hazard ratio [HR] 0.551, 95 % confidence interval [CI] 0.328–0.927, P = 0.025) and PFS (HR 0.409, 95 % CI 0.247–0.676, P < 0.001).

Conclusions

Positive expression of Syn was associated with reduced PFS and OS, while positive CD56 expression was correlated with a shorter OS in HGNEC. The TNM stage was an independent risk factor that significantly influenced PFS and OS in patients with HGNEC. More studies are needed to make further progress in future treatment.