CXCR2 expression in lung neuroendocrine neoplasms.

Abstract

e20143 Background: The incidence of lung neuroendocrine neoplasms (NENs), which account for 1%-3% of all lung malignancies, has been increasing in recent years. Lung NENs range from low-grade typical carcinoid tumor, to intermediate-grade atypical carcinoid tumor, to aggressive high-grade neuroendocrine carcinoma (small cell and large cell neuroendocrine carcinoma). C-X-C Motif Chemokine Receptor 2 (CXCR2) is a G protein-coupled receptor for chemokine interleukin-8 (IL-8), and previous studies suggested that IL-8/CXCR2 pathway may drive the neuroendocrine cell differentiation; however, the expression levels and functional roles of CXCR2 in lung NENs have not been studied. Methods: The expression levels of CXCR2 in lung typical carcinoid (TC) tumors, atypical carcinoid (AC) tumors, and high-grade neuroendocrine carcinomas (HGNEC, including small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC)) were examined by immunohistochemistry using anti-CXCR2 antibody (clone 6C6, BD Biosciences). The immunostaining of CXCR2 was scored by pulmonary pathologists using the intensity of labeling (1 = weak, 2 = moderate, 3 = strong) and percentage of positive tumor cells (1–100%), with the product of these two parameters yielding an H-score (ranged from 0 to 300). The H-scores in three groups were compared using one-way analysis of variance (ANOVA) with multiple groups comparison, P ≤ 0.05 was considered statistically significant. Results: 25 TCs, 18 ACs, and 18 HGNECs (14 SCLC, 1 LCNEC, 3 SCLC and LCNEC combined) were examined. All TC and AC tumors were from resection specimens, the HGNEC group included 10 transbronchial biopsies and 8 resection cases. CXCR2 expression levels did not differ significantly between the TC and AC tumors (mean 182.2 versus 159.7, P = 0.5211), despite a slight reduction in the AC group. HGNECs showed significantly reduced CXCR2 expression compared to the TC (25.2 versus 182.2, P < 0.0001) and AC (25.2 versus 159.7, P < 0.0001) tumors. Using H-score ≤ 20 to define negative staining, 83% (15/18) HGNECs were negative for CXCR2 expression, while none of TCs and only 5.6% (1/18) of ACs showed negative staining. When compared HGNECs to all carcinoid tumors (TCs + ACs), CXCR2 loss demonstrated 83% sensitivity and 98% specificity for distinguishing HGNECs from carcinoid tumors. Conclusions: Our data indicates that pulmonary HGNECs lost CXCR2 expression in comparison to typical and atypical carcinoid tumors, although the underlying mechanism is not clear. CXCR2 might be a valuable diagnostic marker in distinguishing HGNEC from carcinoid tumor in challenging diagnostic scenarios for pathologists. Analysis of the correlation between CXCR2 expression and tumor clinicopathologic characteristics is underway.