Resected Lung Squamous Cell Carcinoma Research Articles

Abstract 1913: FGFR1 amplification as a druggable target in lung squamous cell carcinoma.

Abstract Background: Focal gene amplification is a potential target for diagnosis and therapy in cancer. Fibroblast growth factor receptor-type 1 (FGFR1) may play a role in the pathogenesis of lung squamous cell carcinoma (LSCC) and amplification of the FGFR1 gene is considered a candidate target for treatment of LSCC. The aim of this study was to simultaneously explore copy number changes of FGFR1 and 23 other genes by multiplex ligation-dependent probe amplification (MLPA), to compare the results with fluorescent in situ hybridization (FISH) data, and determine the clinicopathological significance of gene amplification. Methods: This study included 81 resected LSCC specimens obtained between 2008 and 2010, and 14 lung cancer cell lines. MLPA was performed using fresh tumor samples and cell lines and FISH was applied to formalin-fixed, paraffin-embedded tissues. Results: MLPA showed amplification/gain of MYC (48.1% of LSCCs), AURKA (44.4%), MET (29.6%), KIT (21.0%), and FGFR1 (14.8%). FISH showed FGFR1 amplification in 22 LSCCs (27.2%) using a cut-off value of ≥5. There was high concordance between FISH and MLPA (85.2%). No association between FGFR1 amplification and any clinicopathological variables was observed; however, associations were identified between EGFR and FGFR1 FISH-amplified tumors; PDGFRA and poor differentiation; KDR, ABL1, and MET and age; and SMO and CCND2 and pT stages. Conclusions: Our MLPA and FISH data showed that FGFR1 amplification is a common event, occurring in 15-27.2% of LSCCs. Other amplified genes may be also candidate targets for the treatment of LSCC. Citation Format: Mi Jung Kwon, Seung Eun Lee, Joungho Han, Jin Seok Ahn, Keunchil Park, Jhingook Kim, Myung-Ju Ahn, Yoon-La Choi. FGFR1 amplification as a druggable target in lung squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1913. doi:10.1158/1538-7445.AM2013-1913

Abstract 4147: Ratio of miR-146b/miR-191 in serum predicts prognosis in surgically resected lung squamous cell carcinomas

Abstract Background: We profiled 61 lung squamous cell carcinomas (SCC) and 10 matched adjacent normal lung tissue using the Ambion mirVana Bioarray that contains 328 human micro-RNA (miR) probes (Raponi et al. Cancer Research 2009). MiR-146b and miR-191 showed the strongest prediction accuracy for stratifying the prognostic groups. We hypothesize that these miRs can be detectable in serum and its expression in serum might be prognostic. Methods: Using the mirVana PARIS kit (Ambion), total RNA was isolated from 0.5 ml serum samples from 60 resected lung SCC patients, 30 healthy controls and 17 patients with benign lung disease. Reverse transcription reaction using Megaplex RT primers (Applied Biosystems) and preamplification using Megaplex PreAmp primers (Applied Biosystems) were performed. Expression of mature miRs, miR-146b and miR-191, were examined by real-time quantitative polymerase chain reaction using the comparative cycle threshold (Ct) method. Since the normalization of miRNA data in blood samples is still controversial, the ratio between the expression values of miR-146b and miR-191 was calculated and data log transformed. Results: miR-146b and miR-191 expression was detectable in the serum from all lung SCC patients and the serum miR-146b/miR-191 ratio was significantly higher in lung SCC patients (0.29±0.25) than in cancer-free subjects (0.16±0.11) (p-value=0.001). The miR-146b/miR-191 ratio showed a modest discriminative receiver-operator characteristic (ROC) curve, distinguishing cancer patients from cancer-free subjects with areas under the ROC curve at 0.69 (95% CI 0.59-0.79). In 20 SCC patients, the primary tumor miR-146b/miR-191 ratio (calculated using our microarray data) was compared with the miR ratio in serum and a significant correlation was observed (Pearson coefficient=0.455; p-value<0.001). Median overall survival of patients with high miR-146b/miR-191 ratio was significantly shorter (2.25 years ±0.32) than in patients with low miR ratio (5 years ±0.23, log-rank p-value=0.020). After adjusting by clinical covariates (sex, age and stage), miR-146b/miR-191 ratio remained as independent prognostic markers individually. Using the median of miR-146b/miR-191 ratio as a cutoff, the adjusted hazard ratio (HR) for death in those patients with higher miR ratio was 2.24 (95% CI 1.18-4.23). A validation of this miR-146b/miR-191 ratio as a prognostic marker in an independent cohort of resected lung SCC is warranted. Conclusions: Serum miR-146b/miR-191 ratio was significantly higher in lung SCC patients than in cancer-free subjects, but its accuracy to detect lung cancer is limited. Serum miR-146b/miR-191 ratio was significantly correlated with the primary tumor expression and the serum expression has a potential utility as independent prognostic marker in resected lung SCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4147. doi:1538-7445.AM2012-4147

Clinicopathologic characteristics of peripheral squamous cell carcinoma of the lung.

Squamous cell carcinoma of the lung can be divided into two types according to the location of the primary site: the central type and the peripheral type. The clinicopathologic factors in the peripheral type of lung squamous cell carcinoma have not yet been fully evaluated. A total of 204 surgically resected lung squamous cell carcinomas were reviewed with special reference to their location, histologic characteristics based on tumor growth patterns, and clinicopathologic factors. The central type and the peripheral type accounted for 95 and 109 cases, respectively. Although the patient population of the peripheral type was older, with a lower pathologic stage, lower lymphatic vessel involvement, and lymph node metastasis, the Kaplan-Meier survival proportions did not differ significantly between these two groups. Based on the histologic growth pattern, the peripheral type was classified under three subgroups as follows: 1). the alveolar space-filling type, 2). the expanding type, and 3). the combined type. Among these three types, the alveolar space-filling type showed neither lymphatic vessel invasion nor lymph node metastasis and had the most favorable prognosis. The central and peripheral types of lung squamous cell carcinoma have different clinicopathologic characteristics and should be classified under respectively different categories.