Abstract
According to the 2015 World Health Organization classification of lung tumors, pulmonary large cell neuroendocrine carcinoma (PLCNC) is grouped with the small cell lung cancer (SCLC) and carcinoid as pulmonary neuroendocrine carcinoma (PNC) for the common features of neuroendocrine characteristics. Molecular profiles and prognosis of primary pulmonary neuroendocrine carcinoma (PNC) are not well investigated currently. We conducted present study to evaluate genomic abnormality and survivals in patients with primary PNC. Tumor samples of PNC after completely resection from Zhejiang Cancer Hospital were collected from 2008 to 2015. Nine driver genes including six mutation (EGFR, KRAS, NRAS, PIK3CA, BRAF, HER2) and three fusions (ALK, ROS1, RET) were evaluated by RT-PCR. Survival analysis was evaluated using the Kaplan-Meier method. Totally, 108 patients with pathologic confirmed PNC were enrolled. Samples included 52 PLCNC, 44 small cell lung cancer (SCLC) and 12 carcinoid. Twelve patients were found to harbor genomic aberrations (11.1%). The most frequent gene abnormality was PIK3CA (n=5, 4.6%), followed with EGFR (n=3, 2.8%), KRAS (n=2, n=1.9%), ALK (n=1, 0.9%), RET (n=1,0.9%). No ROS1, BRAF, NRAS and HER2 mutations were observed. The frequencies of gene aberrations in PLCNC, SCLC and carcinoid were 15.4%, 6.8% and 8.3%, respectively. Sixty-seven patients were with recurrence or metastasis after surgery, including 32 PLCNC, 33 of SCLC, and two of carcinoid (both were atypical carcinoid). Among the 32 patients with PLCNC, none received molecular targeted treatment, 28 received first-line chemotherapy, including 18 of etoposide/platinum regimen and 10 of other platinum-based treatment. The progression free survival in patients with etoposide/platinum regimen was longer than patients with non-etoposide/platinum treatment (4.8 vs. 3.4 months, P=0.019). Survival difference was observed among the PLCNC, SCLC and carcinoid group (37.0 vs. 34.0 vs. not reached, P=0.035), but no difference existed between the PLCNC and SCLC group (P=0.606). Common genomic abnormality is rare in PNC patients and most frequently observed in PLCNC. Patients with carcinoid had a superior survival than PLCNC and SCLC.
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