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Supplementary Information - PDF file 109K, Legends for Supplementary Figures 1-11

Supplementary Table 1 - PDF file 57K, Clinicopathological information of the NSCLC tissue microarray specimens analyzed by IHC analysis

Purpose: The ETS2 transcription factor is an evolutionarily conserved gene that is deregulated in cancer. We analyzed the transcriptome of lung adenocarcinomas and normal lung tissue by expression profiling and found that ETS2 was significantly downregulated in adenocarcinomas. In this study, we probed the yet unknown functional role of ETS2 in lung cancer pathogenesis.Experimental Design: Lung adenocarcinomas (n = 80) and normal lung tissues (n = 30) were profiled using the Affymetrix Human Gene 1.0 ST platform. Immunohistochemical (IHC) analysis was conducted to determine ETS2 protein expression in non–small cell lung cancer (NSCLC) histologic tissue specimens (n = 201). Patient clinical outcome, based on ETS2 IHC expression, was statistically assessed using the log-rank and Kaplan–Meier tests. RNA interference and overexpression strategies were used to assess the effects of ETS2 expression on the transcriptome and on various malignant phenotypes.Results:ETS2 expression was significantly reduced in lung adenocarcinomas compared with normal lung (P < 0.001). Low ETS2 IHC expression was a significant predictor of shorter time to recurrence in NSCLC (P = 0.009, HR = 1.89) and adenocarcinoma (P = 0.03, HR = 1.86). Moreover, ETS2 was found to significantly inhibit lung cancer cell growth, migration, and invasion (P < 0.05), and microarray and pathways analysis revealed significant (P < 0.001) activation of the HGF pathway following ETS2 knockdown. In addition, ETS2 was found to suppress MET phosphorylation and knockdown of MET expression significantly attenuated (P < 0.05) cell invasion mediated by ETS2-specific siRNA. Furthermore, knockdown of ETS2 augmented HGF-induced MET phosphorylation, cell migration, and invasion.Conclusion(s): Our findings point to a tumor suppressor role for ETS2 in human NSCLC pathogenesis through inhibition of the MET proto-oncogene. Clin Cancer Res; 19(13); 3383–95. ©2013 AACR.

Supplementary Table 2 - XLSX file 92K, Gene features significantly differentially expressed in lung cancer cells transfected with ETS2-specific siRNA compared to cells transfected with control siRNA

Supplementary Figures 1-11 - PDF file 905K, Supplementary Figure 1. Decreased ETS2 expression in smoker lung adenocarcinomas compared to adenocarcinomas from never-smoker patients. Supplementary Figure 2. ETS2 expression in never-smoker and smoker lung cancer cell lines. Supplementary Figure 3. IHC analysis of ETS2 protein in NSCLC FFPE histological tissue specimens. Supplementary Figure 4. Over-expression of ETS2 decreases lung cancer cell anchorage-dependent and -independent growth. Supplementary Figure 5. Modulation of HGF-mediated gene-interaction network following knockdown of ETS2 in H441 lung cancer cells. Supplementary Figure 6. Increased phospho-MET levels following ETS2 knockdown. Supplementary Figure 7. Over-expression of ETS2 decreases MET phosphorylation in lung cancer cells. Supplementary Figure 8. HGF treatment increases ETS2 levels in lung cancer cells. Supplementary Figure 9. ETS2 inhibits HGF-induced lung cancer cell proliferation and migration. Supplementary Figure 10. IHC analysis of phosphorylated MET protein in NSCLC FFPE histological tissue specimens. Supplementary Figure 11. NSCLC patients with both low ETS2 and high membrane phospho-MET IHC expression exhibit significantly reduced time to recurrence

One of the greatest challenges for older, homebound patients receiving health care is accessibility, particularly following a hospitalization. The current study evaluates the effects of using voice-activated technology in the homes of recently discharged patients and its effects on health care outcomes. Voice-based software was embedded in a smart device, which allowed patients to ask questions and receive answers about their own specific care plan. A pre-post study design was used. Forty-eight patients completed the pre and post survey. There was a 63% reduction in emergency department visits and a 26% reduction in physician calls. There was no change in the number of patients requiring hospitalization. More than one half of patients used the smart device daily for their health care needs. More than 70% of patients believed the device was helpful for their general health care needs and assisted in the achievement of care goals. This is the first study of its kind to evaluate patient engagement and outcomes after the use of a smart device with embedded health care directions. [ Journal of Gerontological Nursing, 48 (12), 17–24.]

This research examines Western Australian (WA) public library collections and the representations of Asia in these collections. Serving the needs of the general public within a certain geographic a...

Australia’s participation in the Eurovision Song Contest and involvement in the organisation of the Asian version of Eurovision (the Eurovision Asia Song Contest) through broadcaster SBS has been celebrated, questioned and criticised. In this article, I examine Australia’s role in the organisation of the Eurovision Asia Song Contest in the context of Australia’s relationship with the region, and what this reveals about Australia’s cultural identity and place in this Asia-Pacific region. If Eurovision was conceived as a post-war project to unify Europe, I argue that for the Eurovision Asia Song Contest to become a reality, it needs to have a framework that takes into account the region’s own historical, political and geo-political contexts rather than having a Eurocentric model imposed on it.

This paper argues that an important part of the work that remains to be done in Asian Australian studies is at the frontline of academia—teaching. In a world of contrarily increasing mobility and cultural apathy, how do we convey the relevance of Asia to students without resorting to the discourses of Asia as the exotic other and/or as a market? In what ways can “Asia literacy” be interpreted for a student body whose identities are becoming both more complex and syncretic? We suggest that university teachers are uniquely positioned to equip students with an understanding of Asia that is more processual than factual and more attitudinal than learnt. Drawing on the experience of teaching over a decade in Perth and Brisbane, we reflect on how the task has changed over the years, what the typical obstacles/barriers faced are, and what students understand Asia literacy to mean in the midst of the political and media discourses surrounding Asia today. Finally, we reflect on how our own experiences of su...

Overexpression and gene amplification of the HER family of receptors and their ligands are important prognostic factors in many solid tumors and treatment targeting these molecules has recently become available. The role of this group of receptors has only rarely been described in thymic epithelial neoplasms and never before in a series of cases consisting exclusively of thymic carcinoma. Twenty-four primary squamous cell carcinomas of the thymus were examined for immunohistochemical expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR (pEGFR), HER2, phosphorylated HER2 (pHER2), HER3, phosphorylated HER3 (pHER3) and their ligands epidermal growth factor (EGF), transforming growth factor-α (TGF-α), amphiregulin and epiregulin. Fluorescence in situ hybridization (FISH) analysis for amplification of the EGFR and HER2 genes was performed including assessment of the copy numbers of EGFR and HER2 gene per cell and the ratio of EGFR and HER2 to centromere 7 and 17, respectively. Significant immunohistochemical expression was observed for EGFR (33.3%), pEGFR (33.3%), HER2 (58.3%), HER3 (45.8%), TGF-α (54.1%), amphiregulin (25.0%) and epiregulin (91.7%). A single case showed HER2 gene amplification by FISH. Increased EGFR and HER2 gene copy numbers were observed in 2 (8.4%) and 18 cases (75%), respectively. Eight cases (33.3%) showed an increased HER2:CEP17 ratio. The results of this study indicate that EGFR and HER2 amplification is a rare event in thymic carcinoma, however, protein expression for HER receptors as well as their ligands is a common finding indicating that targeted therapy directed against these molecules may be considered in the treatment of these tumors.

BACKGROUND AND OBJECTIVES: We investigated a pertussis outbreak characterized by atypical cases, confirmed by polymerase chain reaction (PCR) alone at a single laboratory, which persisted despite high vaccine coverage and routine control measures. We aimed to determine whether Bordetella pertussis was the causative agent and advise on control interventions. METHODS: We conducted case ascertainment, confirmatory testing for pertussis and other pathogens, and an assessment for possible sources of specimen contamination, including a survey of clinic practices, sampling clinics for B pertussis DNA, and review of laboratory quality indicators. RESULTS: Between November 28, 2008, and September 4, 2009, 125 cases were reported, of which 92 (74%) were PCR positive. Cases occurring after April 2009 (n = 79; 63%) had fewer classic pertussis symptoms (63% vs 98%; P < .01), smaller amounts of B pertussis DNA (mean PCR cycle threshold value: 40.9 vs 33.1; P < .01), and a greater proportion of PCR-positive results (34% vs 6%; P < .01). Cultures and serology for B pertussis were negative. Other common respiratory pathogens were detected. We identified factors that likely resulted in specimen contamination at the point of collection: environmentally present B pertussis DNA in clinics from vaccine, clinic standard specimen collection practices, use of liquid transport medium, and lack of clinically relevant PCR cutoffs. CONCLUSIONS: A summer pertussis pseudo-outbreak, multifactorial in cause, likely occurred. Recommendations beyond standard practice were made to providers on specimen collection and environmental cleaning, and to laboratories on standardizing PCR protocols and reporting results, to minimize false-positive results from contaminated clinical specimens.

Purpose: The inhibition of c-Src results in a striking reduction in cancer cell invasion, but the effect on cell survival is modest. Defining mechanisms that limit apoptosis following c-Src inhibition could result in an ideal therapeutic approach that both inhibits invasion and leads to apoptosis. In this regard, we discovered a novel feedback loop that results in STAT3 reactivation following sustained c-Src inhibition. Here we define the mechanism underlying this feedback loop and examine the effect of inhibiting it in vivo. Experimental Design: We measured levels and activity of pathway components using PCR, Western blotting, and kinase assays following their manipulation using both molecular and pharmacologic approaches. We used a heterotransplant animal model in which human oral squamous cancer is maintained exclusively in vivo. Results: Following c-Src inhibition, STAT5 is durably inhibited. The inhibition of STAT5A, but not STAT5B, subsequently reduces the expression of suppressors of cytokine signaling 2 (SOCS2). SOCS2 inhibits Janus kinase 2 (Jak2) activity and Jak2–STAT3 binding. SOCS2 expression is necessary for STAT3 inhibition by c-Src inhibitors. Overexpression of SOCS2 is adequate to prevent STAT3 reactivation and to enhance the cytotoxic effects of c-Src inhibition. Likewise, the combination of Jak and c-Src inhibitors led to significantly more apoptosis than either agent alone in vivo. Conclusions: To our knowledge, ours is the first study that fully defines the mechanism underlying this feedback loop, in which sustained c-Src inhibition leads to diminished SOCS2 expression via sustained inhibition of STAT5A, allowing activation of Jak2 and STAT3, Jak2–STAT3 binding, and survival signals. Clin Cancer Res; 18(1); 127–39. ©2011 AACR.

Purpose: We investigated the feasibility, safety, and biologic activity of adenovirus-mediated p53 gene transfer in patients with locally advanced bladder cancer. Patients and Methods: Patients with measurable, locally advanced transitional-cell carcinoma of the bladder who were not candidates for cystectomy were eligible. On a 28-day cycle, intravesical instillations of INGN 201 (Ad5CMV-p53) were administered on days 1 and 4 at three dose levels (1010 particles to 1012 particles) or on either 4 or 8 consecutive days at a single dose level (1012 particles). Results: Thirteen patients received a total of 22 courses without dose-limiting toxicity. Specific transgene expression was detected by reverse transcriptase polymerase chain reaction in bladder biopsy tissue from two of seven assessable patients. There were no changes in p53, p21waf1/cip1, or bax protein levels in bladder epithelium evident from immunohistochemical analysis of 11 assessable patients. Outpatient administration of multiple courses was feasible and well tolerated. A patient with advanced superficial bladder cancer showed evidence of tumor response. Conclusion: Intravesical instillation of Ad5CMV-p53 is safe, feasible, and biologically active when administered in multiple doses to patients with bladder cancer. Observations from this study indicate that this treatment has an antitumor effect in superficial transitional-cell carcinoma. Improvements in the efficiency of gene transfer and the levels of gene expression are required to develop more effective gene therapy for bladder cancer.

It is said that pictures tell a thousand words, but to Malaysian Prime Minister Dr Mahathir, the images of Australian soldiers pointing guns at suspected militiamen in East Timor made one word stand out: ‘belligerent’. Images that meant one thing in Australia represented quite different and often opposite meanings in Southeast Asia. In the Australian press, the Australian soldiers were constructed as ‘the good guys’ helping out a neighbouring country in trouble. The press in some Southeast Asian countries told quite a different story — that of the Australian soldiers as intimidating and therefore the ‘bad guys’ of the region. Through a textual analysis of these images, this paper examines the ways in which the Australian soldiers have been represented in the press in Southeast Asia. This paper also discusses the role the reading of these images played in negotiating Australia's role in East Timor and the region.

Purpose: The ETS2 transcription factor is an evolutionarily conserved gene that is deregulated in cancer. We analyzed the transcriptome of lung adenocarcinomas and normal lung tissue by expression profiling and found that ETS2 was significantly downregulated in adenocarcinomas. In this study, we probed the yet unknown functional role of ETS2 in lung cancer pathogenesis. Experimental Design: Lung adenocarcinomas (n = 80) and normal lung tissues (n = 30) were profiled using the Affymetrix Human Gene 1.0 ST platform. Immunohistochemical (IHC) analysis was conducted to determine ETS2 protein expression in non–small cell lung cancer (NSCLC) histologic tissue specimens (n = 201). Patient clinical outcome, based on ETS2 IHC expression, was statistically assessed using the log-rank and Kaplan–Meier tests. RNA interference and overexpression strategies were used to assess the effects of ETS2 expression on the transcriptome and on various malignant phenotypes. Results: ETS2 expression was significantly reduced in lung adenocarcinomas compared with normal lung (P < 0.001). Low ETS2 IHC expression was a significant predictor of shorter time to recurrence in NSCLC (P = 0.009, HR = 1.89) and adenocarcinoma (P = 0.03, HR = 1.86). Moreover, ETS2 was found to significantly inhibit lung cancer cell growth, migration, and invasion (P < 0.05), and microarray and pathways analysis revealed significant (P < 0.001) activation of the HGF pathway following ETS2 knockdown. In addition, ETS2 was found to suppress MET phosphorylation and knockdown of MET expression significantly attenuated (P < 0.05) cell invasion mediated by ETS2-specific siRNA. Furthermore, knockdown of ETS2 augmented HGF-induced MET phosphorylation, cell migration, and invasion. Conclusion(s): Our findings point to a tumor suppressor role for ETS2 in human NSCLC pathogenesis through inhibition of the MET proto-oncogene. Clin Cancer Res; 19(13); 3383–95. ©2013 AACR.

Purpose: To determine the frequency of estrogen receptor α and β and progesterone receptor protein immunohistochemical expression in a large set of non–small cell lung carcinoma (NSCLC) specimens and to compare our results with those for some of the same antibodies that have provided inconsistent results in previously published reports. Experimental Design: Using multiple antibodies, we investigated the immunohistochemical expression of estrogen receptors α and β and progesterone receptor in 317 NSCLCs placed in tissue microarrays and correlated their expression with patients' clinicopathologic characteristics and in adenocarcinomas with EGFR mutation status. Results: Estrogen receptors α and β were detected in the nucleus and cytoplasm of NSCLC cells; however, the frequency of expression (nucleus, 5-36% for α and 42-56% for β; cytoplasm: Conclusions: Estrogen receptor α and β expression distinguishes a subset of NSCLC that has defined clinicopathologic and genetic features. In lung adenocarcinoma, estrogen receptor α expression correlates with EGFR mutations. (Clin Cancer Res 2009;15(17):5359–68)

Advances in prevention and treatment of non-small cell lung cancer (NSCLC) are dependent in part on the characterization of tumor suppressor genes and oncogenes and the roles they elicit in the pathogenesis of this malignancy. Although v-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) is a canonical transcription factor that regulates various cancer-associated cellular and developmental processes including proliferation and migration, its function in lung carcinogenesis is still unknown. In this study we sought to examine the role of ETS2 in NSCLC pathogenesis. We first examined ETS2 mRNA expression in lung adenocarcinomas (n=80) and normal lung (n=30) which we profiled using microarrays, and in seven matched adenocarcinoma and normal lung pairs analyzed using next-generation sequencing technology. Both array and sequencing datasets revealed that ETS2 mRNA was significantly lower in lung adenocarcinomas relative to normal lung (p 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 2177. doi:1538-7445.AM2012-2177

Background. The folate pathway is active in several cancers including malignant pleural mesothelioma (MPM). Membrane receptors folate receptor alpha (FRα), reduced folate carrier 1 (RFC1), proton coupled folate transporter (PCFT) and the enzyme thymidylate synthase (TS) regulate intra-cellular uptake of folate molecules and antifolate drugs. Due to the documented overexpression of folate markers in MPM they arise as potential targets for novel specific therapies with humanized monoclonal anti-FRα antibody and also to antifolate chemotherapy with pemetrexed. Material and Methods. We studied 79 surgically resected MPM (43 epithelioid, 28 biphasic and 13 sarcomatoid histology types). Protein expression of FRα, RFC1, PCFT and TS was examined by immunohistochemistry (IHC) in FFPE tissues placed in tissue microarray platform and results correlated to clinical-pathologic characteristics. Gene expression and DNA copy number changes of the FRα gene (FOLR1) were examined in 53 mesothelioma tumors using Affymetrix U133 Plus 2.0 microarray's and Illumina HumanOmni1-Quad v1.0 chips, respectively. The expression microarray data was analyzed in the GeneSpring GX 11 software (Agilent technologies Inc.) while DNA copy number changes were detected using the Nexus 5.0 software (BioDiscovery Inc.). Results. MPM frequently showed protein over-expression of FRα, RFC1 and PCFT. Nuclear TS expression positively correlated (P0) had a lower hazard ratio than those who did not (HR=0.309; 95%CI 0.159, 0.601; P=0.0005). Patients with any level (score >0) of cytoplasmic PCFT had lower hazard ratio than those with absence of the marker (HR=0.539; 95%CI 0.306, 0.952; P=0.0332). Our gene expression data analysis on 53 mesothelioma tumors showed greater than 2-fold increase in the FOLR1 and 3-fold increase in the TYMS messenger RNA levels compared to paired normal tissue. Additionally, at least 7 of these tumors show increased gene copy number at the FOLR1 locus (Ch11q 13.4). Conclusions. Folate membrane transporters (FRα, RFC1, PCFT) and the enzyme TS are frequently over expressed in MPM tumor tissues, and PCFT and TS are associated with tumors’ clinico-pathological features. The high level of expression of FRα in MPM supports the rational use of potential utilization of humanized monoclonal anti-FRα antibody and also standard antifolate chemotherapy in this disease. Supported by grant US DoD W81XWH-07-1-0306, ASCO CDA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4121. doi:10.1158/1538-7445.AM2011-4121

Background: Most invasive lung adenocarcinomas (LAC) consist of mixed histological growth patterns including a non-invasive component referred as bronchioloalveolar carcinoma (BAC). Invasive LACs with BAC features are suspected to evolve from pure non-invasive (BAC) tumors. However, in this tumor type there is limited information about the molecular abnormalities associated to the progression from non-invasive to the invasive components. Materials and methods: To perform a detailed mapping analysis of molecular abnormalities comparing non-invasive and invasive sites in lung AC with BAC features we selected archival tumor tissue specimens from 77 LACs with more than 10% of non-invasive component out of 553 available tumors. Using whole histologic sections, we analyzed on each component (non-invasive and invasive) the immunohistochemical (IHC) expression of five markers known to be deregulated in lung AC, including EGFR, Her2-Neu, TTF-1, BRG1 and p53. We also compared in both tumor components the status of EGFR gene copy number gain (CNG) by fluorescent in situ hybridization and mutation of EGFR (exon 18-21) and KRAS (codons 12 and 13) by PCR-based sequencing using DNA extracted from microdissected tissue. For EGFR, we defined 2 types of CNGs: low (trysomy and low-polysomy), and high (high-polysomy and amplification). Results: Most cases had similar levels of expression in the non-invasive and invasive components of LAC for all IHC markers: EGFR, 54/70, 77%; Her2-Neu, 56/71, 79%; p53, 58/72, 80%; TTF-1, 57/71, 80%; and BRG1, 70/73, 96%. In a subset of cases, we found that the invasive component of LAC showed higher frequency of overexpression than non-invasive sites of EGFR (invasive 14/70, 20% vs. non-invasive 2/70, 3%) and Her2Neu (13/71, 18% vs. 2/71, 3%). EGFR mutations of exons 18-21 were found in 11/44 (20%) LAC, and in 7 (64%) mutant tumors the mutations were detected only in the invasive component. KRAS mutations were found in 14/56 (25%) tumors, and in all mutant tumors the mutations were found in both the non-invasive and corresponding invasive components. Any EGFR CNG was found in the invasive component of 20/56 (36%) tumors, including 9 cases with high CNG (4 high-polysomy and 5 gene amplification). In most (16/20, 80%) tumors the invasive component demonstrated higher CNG levels than the corresponding non-invasive sites. Interestingly, all 5 invasive tumors with EGFR amplification did not show such of abnormality in the corresponding non-invasive site. Conclusions: Our findings suggest that in LAC with BAC features the overexpression of EGFR and Her2Neu, and EGFR gene abnormalities (CNGs and mutations) are associated with the progression of non-invasive to invasive components of the tumors. In contrast, in LAC with KRAS mutation this abnormality commences at the non-invasive stage of tumor development. Supported by grant from Uniting Against Lung Cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1417. doi:10.1158/1538-7445.AM2011-1417

Background: Lung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) accounts for ∼80% of all lung cancers. Brain metastases (BMs) are estimated to occur in up to 40% of patients with NSCLC. DNA copy number changes are common in cancer and lead to altered expression and function of genes residing within the affected region of the genome. The aim of this study was to compare DNA copy number abnormalities between primary tumors (PT) and their corresponding BM in NSCLC to identify genomic regions associated with BM development by using array comparative genomic hybridization (aCGH). Material and Method: From surgically resected NSCLC formalin-fixed and paraffin-embedded (FFPE) tissues, we selected 28 paired PTs and BMs (24 adenocarcinomas, and 4 squamous cell carcinomas, SCCs), and 55 additional BMs (43 adenocarcinomas, 2 SCCs, and 10 NSCLCs) specimens for analysis. Using DNA extracted from FFPE tumor tissues we performed oligo-based aCGH in 10 paired PT and BM adenocarcinomas. Statistical aberration detection algorithms of data were conducted by aCGH with Nexus Copy Number software v5.0. Immunohistochemical (IHC) analysis of two proteins (PSCA and LY6K) coded by genes located in 8q24.3 region was performed in both PT and BM specimens. Results: In the aCGH analysis, multiple chromosomal regions with significant (P≤0.05) copy number gain and loss were detected. Whereas PT demonstrated 32 regions (harboring 933 genes) of copy number gain and 16 regions (108 genes) of copy number loss, BM showed 31 regions (1274 genes) with gains and 16 regions (90 genes) with losses. BM demonstrated significantly (P≤0.01) higher frequency of copy number gains in 3 chromosomal regions: 8q24.3 (BM 100% vs. PT 40%), 19q13.33 (BM 90% vs. PT 20%), and 20q13.12 (BM 60% vs. PT 0%). The 8q24.3 region with copy number gain in tumors harbors 7 genes, including Prostate Stem Cell Antigen (PSCA) and Lymphocyte Antigen 6 Complex Locus K (LY6K). Interestingly, in our IHC analysis, BMs (n=84; mean score 141.8) showed a significantly (P=0.008) higher score of expression of PSCA than the corresponding PTs (n=27; mean score 97.8). Similar significant differences were detected when we analyzed only adenocarcinomas samples. No significant differences in the level of IHC expression was detected comparing BMs (n=83; mean score 64) and PTs (n=27; mean score 68.5) for LY6K. Conclusions: By aCGH and subsequent protein expression analysis we have identified that PSCA may play an important role in the development of NSCLC brain metastasis. Similarly to prostate cancer, PSCA represents a novel potential marker for NSCLC metastasis and therapeutic target for advanced lung tumors. Supported by grant US DoD W81XWH-07-1-0306 and Jimmy L Hewlett Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5166. doi:10.1158/1538-7445.AM2011-5166

Non-small cell lung cancer (NSCLC) represents the majority (85%) of lung cancers and is comprised mainly of adenocarcinomas and squamous cell carcinomas (SCCs). The sequential pathogenesis of lung adenocarcinomas and SCCs occurs through dissimilar phases as the former tumors typically arise in the lung periphery whereas the latter normally arise near the central airway. We assessed the expression of SOX2, an embryonic stem cell transcriptional factor that also plays important roles in the proliferation of basal tracheal cells and whose expression is restricted to the main and central airways and bronchioles of the developing and adult mouse lung, in NSCLC by various methodologies. Here, we found that SOX2 mRNA levels, from various published datasets, were significantly elevated in lung SCCs compared to adenocarcinomas (all p Running title: SOX2 abnormalities in NSCLC Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5166.

8067 Background: Epithelial-mesenchymal transition (EMT) regulates metastatic progression and may have an integral role in the pathogenesis of malignant pleural mesothelioma (MPM), a disease charac...

Introduction:Folate receptor alpha (FRα) and reduced folate carrier-1 (RFC1) regulate uptake of folate molecules inside the cell. FRα is a potential biomarker of tumors response to antifolate chemotherapy, and a target for therapies using humanized monocloncal antibody. Information on the protein expression of these receptors in non–small-cell lung carcinoma (NSCLC) is limited.Material and Methods:Expressions of FRα and RFC1 were examined by immunohistochemistry (IHC) in 320 surgically resected NSCLC (202 adenocarcinomas and 118 squamous cell carcinomas) tissue specimens and correlated with patients’ clinico-pathologic characteristics. Folate receptor α gene (FOLR1) mRNA expression was examined using publicly available microarray datasets. FRα expression was correlated with thymidylate synthase and p53 expression in NSCLCs, and with epidermal growth factor receptor (EGFR) and V-Ki-ras2 Kirsten rat sarcoma viral (KRAS) gene mutations in adenocarcinomas.Results:NSCLC overexpressed FRα and RFC1. In a multivariate analysis, lung adenocarcinomas were more likely to express FRα in the cytoplasm (OR = 4.39; p < 0.0001) and membrane (OR = 5.34; p < 0.0001) of malignant cells than squamous cell carcinomas. Tumors from never-smokers were more likely to express cytoplasmic (OR = 3.35; p