Molecular Profiling and Survival of Completely Resected Primary Pulmonary Neuroendocrine Carcinoma

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Abstract

Micro-Abstract

We investigated the genomic abnormalities and survival in patients with primary pulmonary neuroendocrine carcinoma based on the 2015 World Health Organization classification. The results demonstrated that the frequencies of gene aberrations were 15.4%, 6.8%, and 8.3% in pulmonary large-cell neuroendocrine carcinoma, small-cell lung cancer, and carcinoid, respectively. Survival differences existed among the 3 groups, but no difference existed between pulmonary large-cell neuroendocrine carcinoma and small-cell lung cancer.

Background:

Currently, molecular profiles and prognosis of primary pulmonary neuroendocrine carcinoma (PNC) are poorly elucidated. The present study was designed to evaluate genomic abnormalities and survival in patients with primary PNC.

Methods:

Completely resected PNC samples were collected from Zhejiang Cancer Hospital during the period of 2008 to 2015. Nine driver genes, including 6 mutations (EGFR, KRAS, NRAS, PIK3CA, BRAF, and HER2) and 3 fusions (ALK, ROS1, and RET), were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Survival analysis was conducted by the Kaplan-Meier method.

Results:

A total of 108 patients with pathologically confirmed PNC were enrolled. The types were pulmonary large-cell neuroendocrine carcinoma (PLCNC, n = 52), small-cell lung cancer (SCLC, n = 44), and carcinoid (n = 12). Twelve patients (11.1%) harbored genomic aberrations. The most frequent gene abnormalities in decreasing order were PIK3CA (n = 5, 4.6%), EGFR (n = 3, 2.8%), KRAS (n = 2, 1.9%), ALK (n = 1, 0.9%), and RET (n = 1, 0.9%). No ROS1, BRAF, NRAS, or HER2 mutation was detected. The frequencies of gene aberrations were 15.4%, 6.8%, and 8.3% in PLCNC, SCLC, and carcinoid, respectively. Survival differences existed among PLCNC, SCLC, and carcinoid groups (37.0 vs. 34.0 vs. not reached, P = .035); however, no difference existed between PLCNC and SCLC groups (P = .606).

Conclusions:

Genomic abnormality is rare in patients with PNC and it is the most frequently observed in PLCNC.

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