Lung Squamous Cell Carcinoma Specimens Research Articles

Identification of tumor-suppressor genes in lung squamous cell carcinoma through integrated bioinformatics analyses.

Lung cancer is a prevalent malignancy, and fatalities of the disease exceed 400,000 cases worldwide. Lung squamous cell carcinoma (LUSC) has been recognized as the most common pathological form of lung cancer. The comprehensive understanding of molecular features related to LUSC progression has great significance in LUSC prognosis assessment and clinical management. In this study, we aim to identify a panel of signature genes closely associated with LUSC, which can provide novel insights into the progression of LUSC. Gene expression profiles were retrieved from public resources including gene expression omnibus (GEO) and the cancer genome atlas (TCGA) database. Differentially expressed genes (DEGs) between LUSC specimens and normal lung tissues were identified by bioinformatics analyses. A total of 66 DEGs were identified based on two cohorts of data. CytoHubba plugin of Cytoscape software was utilized for the further analyses of the top 10 candidate hub genes including OGN, ABI3BP, MAMDC2, FGF7, FAM107A, SPARCL1, DCN, COL14A1, and MFAP4 and CHRDL1, which showed significant downregulation in LUSC. Two LUSC cell lines were used to validate the functions of CHRDL1 and FAM107A through overexpression experiment. Together, our data revealed novel candidate tumor-suppressor genes in LUSC, suggesting previously unappreciated mechanisms in the progression of LUSC.

Perilipin1 Expression as a Prognostic Factor in Patients with Squamous Cell Carcinoma of the Lung.

Perilipin (PLIN) is a major structural protein located on the surface of lipid droplets. PLIN plays an important role in human metabolism and is associated with metabolic diseases, such as obesity, diabetes, hypertension, and endocrine disorders. The dysregulation of lipid metabolism is one of the most prominent metabolic changes observed in cancers. Therefore, the PLIN protein family has recently attracted attention owing to its role in lipid metabolism and cancer. To date, no studies have addressed the association between the prognosis of lung cancer and PLIN1 expression. For the first time, we found that high PLIN1 expression was significantly correlated with worse disease-free survival (DFS) in lung squamous cell carcinoma (SCC). We examined PLIN1 expression by the immunohistochemical analysis of surgical lung SCC specimens obtained from 94 patients. We analyzed the correlation between PLIN1 expression, clinicopathological data, and patient survival, using a chi-squared test, Kaplan-Meier analysis with log-rank tests, and the multivariate Cox proportional hazards regression test. High PLIN1 expression was significantly correlated with lower DFS in the Kaplan-Meier analysis and the multivariate Cox proportional hazards regression model. High PLIN1 expression was significantly correlated with worse prognosis in lung SCC.

S100A7 as a founder of immunosuppressive tumor microenvironment shed light on immunotherapy in lung squamous cell carcinoma.

e20541 Background: The application of immune checkpoint inhibitors (ICIs) has revolutionarily improved the prognosis of patients with lung squamous cell carcinoma (LUSC) with limited treatment options, yet only certain patients can benefit from ICIs. S100A7 has been reported to accelerate tumor progression by activating oncogenic pathway in LUSC. Here, we aimed to deepen in the role played by S100A7 in the tumor immune microenvironment (TIME) and immunotherapeutic efficacy. Methods: Immunohistochemical analysis of PD-L1 expression and CD8+ tumor infiltrating lymphocytes (TILs) was applied to investigate the correlation between S100A7 expression and TIME. The mechanism of S100A7 regulating PD-L1 expression and infiltration of CD8+ TILs was then explored. Based on a mouse model and a clinical cohort, the association between S100A7 expression and the efficacy of ICIs was also analyzed. Results: Immunohistochemical analysis of 102 LUSC specimens revealed that S100A7 expression negatively corelated with PD-L1 expression and the infiltration of CD8+ TILs. The in vitro studies showed that S100A7 deregulated PD-L1 expression by activating the p-AKT pathway. Notably, a negative correlation between S100A7 expression and CXCL9 expression in tumor cell and CD68+ macrophage was observed in LUSC samples, which may lead to a decrease in CD8+ TILs. Results of murine models of LUSC revealed that dysregulation of S100A7 exerted an impact on anti-tumor response of immunotherapy. Further analysis showed that targeting S100A7 may enhance the efficacy of immunotherapy by yielding an inflammatory phenotype. In addition, baseline plasma level of S100A7 was higher in patients with progressive disease ( p = 0.0393) based on our cohort of LUSC patients treated with ICIs. The potential predictive value of baseline plasma level of S100A7 for immunotherapy response was then confirmed with area under curve up to 0.869. Multivariate Cox regression analyses revealed that baseline S100A7 level in plasma samples was an independent prognostic factor. Conclusions: This study deepened in the understanding of the role played by S100A7 in the TIME, offering a novel insight of its mechanism of action on immunotherapy resistance. Our results indicated that S100A7 may emerge as a powerful predictive tool for immunotherapy and the treatment targeting S100A7 may be beneficial for immunotherapy in LUSC.

Expression of oncogenic long noncoding RNA PSMG3-antisense 1 in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is one of the most common subtypes of lung cancer that accounts for ~50% of all lung cancer cases. Long noncoding RNA (lncRNA) PSMG3-antisense (AS) 1 has been suggested to play an important role in various types of cancer. Therefore, the aim of the present study was to investigate the role of PSMG3-AS1 using clinical specimens and data from 130 patients with LUSC. The expression levels of PSMG3-AS1 and miR-143-3p were detected in LUSC specimens, and the correlation between lncRNA PSMG3-AS1 expression and patient clinical characteristics was analyzed. Cell Counting Kit-8, Transwell migration and invasion assays were used to investigate the functional role of PSMG3-AS1 in LUSC. The mechanism of PSMG3-AS1 on LUSC cells was also investigated using a luciferase activity assay with wild-type or mutated PSMG3-AS1. PSMG3-AS1 was found to be upregulated in LUSC, and high expression was associated with positive lymph node metastasis and a higher TNM stage. The results of multivariate Cox regression analysis revealed that PSMG3-AS1 may serve as an independent prognostic indicator in LUSC. Furthermore, inhibiting PSMG3-AS1 expression reduced tumor cell proliferative, migratory and invasive abilities. Moreover, PSMG3-AS1 was found to be closely associated with miR-143-3p in LUSC, and thus may become a potential prognostic marker and therapeutic target for the treatment of LUSC in the future.

Abstract 4716: Glutathione S transferase omega 2 (GSTO2) is a novel tumor suppressor gene of human lung squamous cell carcinoma

Abstract Lung cancer is one of the most common malignant diseases and the leading cause of cancer death globally. The clinical, pathologic, and genomic characteristics of lung cancer are very diverse. Non-small cell lung cancer (NSCLC) is the most frequent type of lung cancers and can be histologically classified into lung adenocarcinoma and squamous cell carcinoma (SCC). Lung adenocarcinoma is generally located in alveolar or endobronchial, whereas LSCC frequently arises in bronchi and bronchiole. Molecular-targeted drugs have been developed for lung adenocarcinoma; however, there is currently no definite clinical implication for lung SCC (LSCC). Therefore, to increase the cure and survival rates of lung cancers, developing type-specific diagnostic/prognostic markers and treatment methods might improve this situation. One of the major risk factors of LSCC is smoking, which causes aberrant DNA methylation, abnormal gene expression, and eventually malignant transformation. We previously identified glutathione S-transferase omega 2 (GSTO2) as one of DNA methylation target genes in esophageal SCC (Otsubo T, Oncotarget, 8, 84434-84448, 2017). We reported that GSTO2 was exclusively expressed in nethermost basal cells which are believed to function as stem cells in normal esophageal mucosa. Furthermore, GSTO2 overexpression in esophageal SCC cells significantly inhibited cell growth in vitro and in vivo. (Terayama M, Carcinogenesis, in press). In present study, we investigated the expression and function of GSTO2 in normal lung and LSCC. In normal bronchi and bronchiole containing a variety of epithelial cell populations such as ciliated cells, non-ciliated, columnar Clara cells, and basal cells, GSTO2 was expressed in cytokeratin 5/6-positive airway basal cells. In contrast, all 94 LSCC specimens examined in this study showed no GSTO2 expression. To clarify the significance of GSTO2 silencing LSCC, we restored GSTO2 expression in LK-2 LSCC cells. Overexpression of GSTO2 significantly inhibited cell growth compared with the mock-transfected LK-2 cells. In colony formation assay, GSTO2-transfected cells failed to form colonies, whereas mock-transfected cells formed colonies efficiently. When human LSCC cell lines (LK-2 and EBC-1) were treated with 5-aza-2'-deoxycytidine (5-aza-dC), a DNA-methyltransferase inhibitor, the GSTO2 transcription was induced, indicating that aberrant hypermethylation of the GSTO2 in LSCC was likely the cause of the downregulated expression. Considering its expression in basal cells which are proposed to be the precursor cells of LSCC, the silencing of GSTO2 by DNA hypermethylation may contribute malignant transformation of LSCC. Citation Format: Ryusuke Sumiya, Masayoshi Terayama, Teruki Hagiwara, Keigo Sekihara, Satoshi Nagasaka, Kazuhiko Yamada, Norihiro Kokudo, Yuki I. Kawamura. Glutathione S transferase omega 2 (GSTO2) is a novel tumor suppressor gene of human lung squamous cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4716.

Abstract B071: Genomic differences between non-small cell lung cancer (NSCLC) in African American and white patients

Abstract Background: Racial disparities in lung cancer exist, as African Americans (AAs) have the highest incidence of lung cancer and rate of lung cancer-related death and develop lung cancer at an earlier age compared with other racial groups. Multiple structural determinants of health affect poorer survival in AAs. In addition, evidence suggests that differences in tumor biology also contribute to disparities in clinical outcomes. This work addresses the urgent need to define further the molecular landscape of non-small cell lung cancer (NSCLC) in the AA population in order to drive novel biomarker and therapeutic development and ultimately improve clinical outcomes. Methods: We have analyzed differentially expressed genes (DEGs) and differentially spliced genes (DSGs) between resected formalin-fixed, paraffin-embedded lung squamous cell carcinoma specimens from 20 AA and 20 white patients (self-reported race) using Affymetrix Clariom D Assay, human and Transcriptome Analysis Console Software. To obtain genetically estimated indicators of race, we performed ancestral genotyping. After excluding specimens from biracial patients and those with positive versus negative area under the curve less than 0.6, we used a cohort of 14 specimens from AA patients and 13 specimens from white patients for analysis. Results: Transcriptome analysis revealed 450 DEGs and 7,089 DSGs, in which we identified 13,763 unique splicing events, between NSCLC in AA and white patients. The nuclear receptors meta pathway and the olfactory receptor pathway are over-represented with such DEGs. Seven of the DEGs also exhibit differential expression between lung squamous cell carcinoma in AA and white patients in The Cancer Genome Atlas (TCGA). Twenty-eight of the DEGs also exhibit differential expression between prostate cancer in AA and white patients. Among the 7,089 DSGs between NSCLC in AA and white patients, 599 also exhibit differential splicing between prostate cancer in AA and white patients, 33 also exhibit differential splicing in breast and liver cancer, and 6 also exhibit differential splicing in breast, liver and prostate cancer. Validation of prioritized genomic differences using polymerase chain reaction and investigation of the functional significance of prioritized genomic differences to lung cancer cell biology using CRISPR-Cas9 technology is currently under way. Conclusions: This study identifies novel aggregate gene expression and splicing differences between NSCLC in AA and white patients. Interestingly, the number of DSGs far exceeds the number of DEGs in the same tissues and a number of DEGs and DSGs exhibit differential aggregate gene expression and splicing, respectively, in additional solid tumor types. Upon further study, these mechanisms have the potential to serve as novel targets for the development of biomarkers or therapeutic agents for lung cancer, and to reduce the mortality burden from lung cancer among AAs. Citation Format: April E. Deveaux, Dadong Zhang, Muthana Al Abo, Nadine J. Barrett, Rick A. Kittles, Kouros Owzar, Shannon J. McCall, Jeffrey Crawford, Steven R. Patierno, Jeffrey M. Clarke, Jennifer A. Freedman. Genomic differences between non-small cell lung cancer (NSCLC) in African American and white patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B071.

Transcriptome-based molecular subtyping of non–small cell lung cancer may predict response to immune checkpoint inhibitors

ObjectivesWe set out to investigate whether transcriptome-based molecular subtypes in lung adenocarcinoma and lung squamous cell carcinoma are predictive of the response to programmed cell death 1 blockade. MethodsMolecular classification of non–small cell lung cancer was performed by unsupervised clustering of mRNA sequencing data from 87 lung adenocarcinoma and 101 lung squamous cell carcinoma specimens, and molecular subtypes were characterized according to their immunogenomic determinants. A prediction algorithm of molecular subtypes was applied to 35 patients with non–small cell lung cancer treated with programmed cell death 1 blockade to test its association with treatment response (GSE93157; the Barcelona cohort). ResultsUnsupervised hierarchical clustering of transcriptome sequencing data in lung adenocarcinoma and lung squamous cell carcinoma revealed 3 and 2 distinct clusters, respectively. Cluster 1 in each histology had a higher expression of immune regulatory molecules, increased cytolytic activity, higher interferon-γ signature, and more abundant infiltration of immune cells. Cluster 1 and other cluster(s) in lung adenocarcinoma and lung squamous cell carcinoma had immunologically-hot and immunologically-cold tumor-immune microenvironments, respectively. Immunologically-hot cluster 1 subtype is hereafter referred to as “good-tumor-immune microenvironments” and the other subtypes as “bad-tumor-immune microenvironments.” The “good-tumor–immune microenvironments” subtype in lung adenocarcinoma included a high fraction of CD8 T cells and memory B cells, but a low fraction of regulatory CD4 T cells and tumor-associated myeloid cells. Forward and backward application of our molecular subtyping to the Barcelona cohort revealed that transcriptome-based molecular subtyping is significantly associated with response to programmed cell death 1 blockade. ConclusionsMolecular stratification by transcriptome sequencing data in non–small cell lung cancer identifies distinct immunomolecular subtypes that predict the response to programmed cell death 1 blockade.

A Clinicopathological and Prognostic Analysis of PD-L2 Expression in Surgically Resected Primary Lung Squamous Cell Carcinoma.

Immunotherapy targeting programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has shown dramatic therapeutic effects for lung squamous cell carcinoma (SCC), and PD-L1 expression has been shown not only to be a predictive biomarker for response to immunotherapy but also a prognostic factor for lung SCC. However, the clinical significance of programmed death-ligand 2 (PD-L2), another PD-1 ligand, remains unclear. Therefore, we analyzed PD-L2 expression by immunohistochemistry in surgically resected primary lung SCC. PD-L1 and PD-L2 expression on tumor cells were analyzed in 211 primary lung SCC specimens by immunohistochemistry. Additionally, numbers of CD3+, CD4+, and CD8+ tumor-infiltrating lymphocytes were also examined. The rates of positive PD-L2 expression were 77.3% and 67.3% using 5% and 10% cut-off values, respectively. Low PD-L2 expression on tumor cells was statistically associated with histological type (non-keratinizing/keratinizing) and lymphatic invasion. PD-L2-positive patients had significantly longer postoperative survival time (log-rank test; p = 0.0170 at 5% cut-off and p = 0.0500 at 10% cut-off). Furthermore, survival analysis according to PD-L1 and PD-L2 expression revealed that PD-L1-positive and PD-L2-negative patients had the most unfavorable prognosis. PD-L2 protein expression was associated with prognosis in primary lung SCC patients. PD-L2 expression might be a potential biomarker for response to PD-1/PD-L1-targeted immunotherapy, which should be investigated in future studies.

MiR-223-3p functions as a tumor suppressor in lung squamous cell carcinoma by miR-223-3p-mutant p53 regulatory feedback loop

BackgroundMicroRNAs have an important role in diverse biological processes including tumorigenesis. MiR-223 has been reported to be deregulated in several human cancer types. However, its biological role has not been functionally characterized in lung squamous cell carcinoma (LSCC). The following study investigates the role of miR-223-3p in LSCC growth and metastasis and its underlying mechanism.MethodsMicroRNA profiling analyses were conducted to determine differential miRNAs expression levels in LSCC tumor tissues that successfully formed xenografts in immunocompromised mice (XG) and failed tumor tissues (no-XG). RT-PCR and in situ hybridization (ISH) was performed to evaluate the expression of miR-223-3p in 12 paired adjacent normal tissues and LSCC specimens. Cell proliferation and migration were assessed by CCK-8, colony formation and Transwell assay, respectively. The role of miR-223-3p in LSCC tumorigenesis was examined using xenograft nude models. Bioinformatics analysis, Dual-luciferase reporter assays, Chromatin immunoprecipitation (ChIP) assay and Western blot analysis were used to identify the direct target of miR-223-3p and its interactions.ResultsMiR-223-3p was downregulated in LSCC tissues that successfully formed xenografts (XG) compared with tumor tissues that failed (no-XG), which was also significantly reduced in LSCC tissues compared with the adjacent normal tissues. Gain- and loss-of function experiments showed that miR-223-3p inhibited proliferation and migration in vitro. More importantly, miR-223-3p overexpression greatly suppressed tumor growth in vivo. Mechanistically, we found that mutant p53 bound to the promoter region of miR-223 and reduced its transcription. Meanwhile, p53 is a direct target of miR-223-3p. Thus, miR-223-3p regulated mutant p53 expression in a feedback loop that inhibited cell proliferation and migration.ConclusionsOur study identified miR-223-3p, as a tumor suppressor gene, markedly inhibited cell proliferation and migration via miR-223-3p-mutant p53 feedback loop, which suggested miR-223-3p might be a new therapeutic target in LSCC bearing p53 mutations.

STXBP4 Drives Tumor Growth and Is Associated with Poor Prognosis through PDGF Receptor Signaling in Lung Squamous Cell Carcinoma.

Purpose: Expression of the ΔN isoform of p63 (ΔNp63) is a diagnostic marker highly specific for lung squamous cell carcinoma (SCC). We previously found that Syntaxin Binding Protein 4 (STXBP4) regulates ΔNp63 ubiquitination, suggesting that STXBP4 may also be an SCC biomarker. To address this issue, we investigated the role of STXBP4 expression in SCC biology and the impact of STXBP4 expression on SCC prognosis.Experimental Design: We carried out a clinicopathologic analysis of STXBP4 expression in 87 lung SCC patients. Whole transcriptome analysis using RNA-seq was performed in STXBP4-positive and STXBP4-negative tumors of lung SCC. Soft-agar assay and xenograft assay were performed using overexpressing or knockdown SCC cells.Results: Significantly higher levels of STXBP4 expression were correlated with accumulations of ΔNp63 in clinical lung SCC specimens (Spearman rank correlation ρ = 0.219). Notably, STXBP4-positive tumors correlated with three important clinical parameters: T factor (P < 0.001), disease stage (P = 0.030), and pleural involvement (P = 0.028). Whole transcriptome sequencing followed by pathway analysis indicated that STXBP4 is involved in functional gene networks that regulate cell growth, proliferation, cell death, and survival in cancer. Platelet-derived growth factor receptor alpha (PDGFRα) was a key downstream mediator of STXBP4 function. In line with this, shRNA mediated STXBP4 and PDGFRA knockdown suppressed tumor growth in soft-agar and xenograft assays.Conclusions: STXBP4 plays a crucial role in driving SCC growth and is an independent prognostic factor for predicting worse outcome in lung SCC. These data suggest that STXBP4 is a relevant therapeutic target for patients with lung SCC. Clin Cancer Res; 23(13); 3442-52. ©2017 AACR.

P1.02-041 Characterization of MET-N375S as an Activating Mutation in Squamous Cell Carcinoma of the Lung

Over the years, significant progress has been made in the treatment of lung carcinoma. While targeting EGFR mutations in the tyrosine kinase domain and EML4-ALK rearrangements have yielded impressive therapeutic gains in lung adenocarcinoma; the rarity of genetic aberration in squamous cell carcinoma (SCC) has restricted the use of molecular-targeting agents. Next-Generation sequencing analysis has identified a high frequency of c-MET mutation in Asian lung SCC specimens, in particular the MET-N375S mutant. This study aims to characterize the functional significance and therapeutic implications of MET-N375S in lung SCC cells. MET (N375S) mutation in tumor tissues was verified with droplet digital PCR. c-MET mutant expressing clones were generated through site-directed mutagenesis and single cell clonal selection. The impact of MET-N375S in lung SCC cells was characterized by defining the downstream effectors (Proteome profiling), biological functions (anchorage-independent growth, invasion and migration assays), transciptomic regulation (RNAseq) and protein-protein interaction (SILAC). Novel binding partners of MET-N375S was verified using co-immunoprecipitation (co-IP) and proximity ligation assay (PLA). Sensitivity of c-MET mutant to various kinase inhibitors was determined with CellTiter-Glo assay. MET (N375S) mutation was confirmed in 9/45 lung SCC specimens (20%). Ectopic expression of MET-N375S in lung SCC cells significantly elevated the activation of downstream Src, p38 and ERK1/2 kinases, increased hsp27 expression, while enhanced migratory, invasive and anchorage-independent colony forming ability in vitro. Despite so, comparative transcriptomic analysis revealed that epithelial-mesenchymal signature genes were not induced in cells expressing mutant c-MET. On the contrary, SILAC and co-IP analyses on the MET-N375S interactome demonstrated an increase in binding affinity towards receptor tyrosine kinases (RTKs) as compared to wild type c-MET, which was confirmed with in situ PLA. Moreover, MET-N375S augmented in vitro sensitivity to selective MET inhibitors. These findings suggest the role of MET-N375S as an activating mutation that strongly enhance malignant transformation and metastatic potential in lung SCC cells. Mechanistically, the dysregulation of various oncogenic events could be associated with the formation of heterodimers with RTKs. Clinically, MET-N375S could be utilized as a potential predictive biomarker for patients with advanced SCC of the lung to be treated with selective MET inhibitors.

FGFR gene alterations in lung squamous cell carcinoma are potential targets for the multikinase inhibitor nintedanib.

Fibroblast growth factor receptor (FGFR) gene alterations are relatively frequent in lung squamous cell carcinoma (LSCC) and are a potential targets for therapy with FGFR inhibitors. However, little is known regarding the clinicopathologic features associated with FGFR alterations. The angiokinase inhibitor nintedanib has shown promising activity in clinical trials for non‐small cell lung cancer. We have now applied next‐generation sequencing (NGS) to characterize FGFR alterations in LSCC patients as well as examined the antitumor activity of nintedanib in LSCC cell lines positive for FGFR1 copy number gain (CNG). The effects of nintedanib on the proliferation of and FGFR signaling in LSCC cell lines were examined in vitro, and its effects on tumor formation were examined in vivo. A total of 75 clinical LSCC specimens were screened for FGFR alterations by NGS. Nintedanib inhibited the proliferation of FGFR1 CNG‐positive LSCC cell lines in association with attenuation of the FGFR1–ERK signaling pathway in vitro and in vivo. FGFR1 CNG (10.7%), FGFR1 mutation (2.7%), FGFR2 mutation (2.7%), FGFR4 mutation (5.3%), and FGFR3 fusion (1.3%) were detected in LSCC specimens by NGS. Clinicopathologic features did not differ between LSCC patients positive or negative for FGFR alterations. However, among the 36 patients with disease recurrence after surgery, prognosis was significantly worse for those harboring FGFR alterations. Screening for FGFR alterations by NGS warrants further study as a means to identify patients with LSCC recurrence after surgery who might benefit from nintedanib therapy.

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

Human Papillomavirus Infection in Lung vs. Oral Squamous Cell Carcinomas: A Polymerase Chain Reaction Study

The role of Human Papillomavirus (HPV) has been suspected in pathogenesis of various malignancies; however, the available data are not conclusive. This study aimed to determine and compare the frequency of HPV infection in oral and lung Squamous Cell Carcinoma (SCC) by a sensitive method. Sixty specimens of oral and lung SCC (30 cases each one) were reevaluated in Tabriz Imam Reza Centre in a 24 month period. Following genomic DNA extract, the Polymerase Chain Reaction (PCR) amplification was performed in presence of specific MY11 and MY09 primers for HPV infection. Three cervical specimens and a combination of PCR solution lacking DNA plus healthy persons' DNA samples were employed as positive and negative controls, respectively. The oral group was significantly older than the lung group (68.90 vs. 56.67 y, p < 0.001) with more males in the latter (83.3 vs. 60%; p = 0.04). Percentages of HPV infection in the oral and lung groups were comparable (20 vs. 10%, respectively; p = 0.47). Majority of patients with HPV infection were older than 60 years (88.9%) or male (88.9%). In the oral group, all these cases were well differentiated and the majority was of lower lip origin (83.3%). In the lung group, 66.7% of these specimens were moderately differentiated and the origin was bronchus in all cases. In conclusion, the rate of HPV infection in lung and oral SCC samples is rather lower than the previous reports in the literature. This rate is apparently higher in the oral than the lung SCC specimens.