Clinical Impact of POU2F3 Expression in Surgically Resected Pulmonary High-Grade Neuroendocrine Carcinoma.

OBJECTIVE

High-grade neuroendocrine carcinoma (HGNEC) with dominant POU2F3 expression exhibits non-neuroendocrine features. However, clinical data regarding this subset of pulmonary HGNECs are scarce, and its clinical characteristics remain unclear.

METHODS

Clinicopathological data from 109 patients who underwent surgery for HGNEC were collected and analyzed based on transcription factor expression. Patients were divided into a POU2F3-dominant group (HGNEC-P) and a non-dominant group (HGNEC-non-P) according to immunohistochemical analysis. The clinicopathological characteristics of the two groups were compared, and univariate and multivariate analyses were conducted to identify prognostic factors.

RESULTS

The HGNEC-P group comprised 26 patients, while the HGNEC-non-P group comprised 83 patients. The HGNEC-P group showed significantly lower expression of carcinoembryonic antigen (CEA) (p < 0.001) and a lower rate of vascular invasion (p = 0.021) compared to the HGNEC-non-P group. In addition, the HGNEC-P group exhibited a unique tumor marker profile, with lower serum CEA and higher serum cytokeratin antigen (CYFRA) levels (p < 0.001 and p = 0.046, respectively). Complete resection was achieved in all HGNEC-P cases, whereas only 75.9% of HGNEC-non-P cases achieved complete resection. Multivariate analysis identified POU2F3 expression as an independent prognostic factor for recurrence-free survival (RFS) and disease-specific survival (DSS) (p = 0.037 and p = 0.038, respectively). In patients with pathological Stage I disease, the HGNEC-P group showed significantly better RFS (p = 0.010).

CONCLUSIONS

POU2F3-dominant HGNEC is associated with distinct clinicopathological features and favorable prognosis, particularly in early-stage disease. These findings may support the identification of this subset and inform the development of more effective treatment strategies.