EML4-ALK fusion genes were observed predominantly in adenocarcinomas, in female or nonsmoking populations. Additionally, the EML4-ALK fusions were mutually exclusive with mutations in the EGFR, KRAS, and ERBB2 genes.

Higher levels of FOLR1 appear to be associated with better prognoses for patients with lung adenocarcinomas.

BACKGROUND: The authors elucidated particular chemokine receptors that are expressed on lung cancer cells, as well as the clinical significance of the expression of these chemokine receptors in completely resected nonsmall cell lung cancer (NSCLC). METHODS: The authors examined gene expression of chemokine receptors (CCR1‐11, CXCR1‐7, XCR1, and CX3CR1) in 11 cell lines of lung cancer, and gene expression of CXCR3, CXCR4, and CXCR7 (CXCR3/4/7) in surgical specimens of 127 patients who underwent complete resection for their NSCLC between May 2001 and December 2002, using quantitative real‐time reverse transcriptase–polymerase chain reaction (PCR). Mutation detection analysis of the EGFR genes using the PCR single‐strand conformational polymorphism method was evaluated in patients with pathological (p‐) stage I adenocarcinoma. RESULTS: Substantial expression of CXCR3/4/7 mRNA was observed in all NSCLC cell lines examined. In p‐stage I NSCLC, CXCR4 and CXCR7 expression values in patients with postoperative metastatic recurrence (Rec‐Distant) were significantly higher than in those without recurrences (P = .003 and P = .007, respectively). In addition, the 5‐year disease‐free survival (DFS) rate of high CXCR7‐expressing patients (63.2%) was significantly lower than that of low CXCR7‐expressing patients (84.8%) (P = .033). The EGFR mutation was significantly more frequent in patients with higher CXCR7 expression (14 of 21 patients) than in those with lower CXCR7 expression (12 of 32 patients) (P = .038). A multivariate analysis confirmed that high CXCR7 expression was an independent and significant factor predicting a poor DFS in p‐stage I NSCLC patients (P = .041). CONCLUSIONS: Higher expression of CXCR7 is associated with Rec‐Distant and poor DFS in patients with p‐stage I NSCLC. Cancer 2009. © 2009 American Cancer Society.

Keap1 gene mutations are likely to be associated with a worse prognosis and lower postoperative disease-free survival rates in pathological Stage I-II NSCLC.

The tumor microenvironment is crucial to the progression of various malignancies. Malignant pleural mesothelioma (MPM), which originates from the pleura, grows aggressively in the thoracic cavity. Here we describe an orthotopic implantation SCID mouse model of MPM and demonstrate that α-SMA-positive fibroblast-like cells accumulate in the tumors produced by the human MPM cell lines MSTO-211H and Y-Meso-14. We assessed the interaction between MPM cells and their microenvironments, focusing on tumor-associated fibroblasts. MSTO-211H and Y-Meso-14 cells produced fibroblast growth factor-2 (FGF-2) and/or platelet-derived growth factor-AA (PDGF-AA); they also enhanced growth, migration, and production of hepatocyte growth factor (HGF) by human lung fibroblast MRC-5 cells. MRC-5 cells stimulated HGF-mediated growth and migration of MSTO-211H and Y-Meso-14 cells in an in vitro coculture system. In the orthotopic model, tumor formation by MSTO-211H and Y-Meso-14 cells was significantly inhibited by TSU-68, an inhibitor of FGF, VEGF, and PDGF receptors; imatinib, an inhibitor of PDGF receptors; and NK4, an antagonist of HGF. Histological analyses of clinical specimens from 51 MPM patients revealed considerable tumor-associated fibroblasts infiltration and expression of HGF, together with FGF-2 or PDGF-AA, in tumors. These findings indicate that MPM instigates tumor-associated fibroblasts, promoting tumor progression via a malignant cytokine network. Regulation of this cytokine network may be therapeutically useful for controlling MPM.

ADAM12-L mRNA expression is an independent prognostic factor in resected p-stage I lung adenocarcinoma, and is significantly correlated with tumor differentiation stage and postoperative cancer recurrence.

D2-40 expression on tumor cells was more frequently seen in SCC than in adenocarcinoma of the lung. In addition, D2-40 expression on lymphatic vessels in tumor tissues was a statistically significant prognostic factor in SCC.

Malignant pleural mesothelioma (MPM) is an aggressive thoracic tumor with a poor prognosis. We performed a comprehensive clinical study on the intratumoral expression of Wnt1, Wnt2B and Wnt5A in MPM. One hundred and seven MPM patients were investigated. Immunohistochemistry was performed to evaluate the intratumoral expression of Wnt1, Wnt2B, Wnt5A, survivin and c-Myc, and the Ki-67 proliferation index. The apoptotic index was evaluated by the TUNEL method. Among the 107 MPMs, 23 MPMs (21.5%) were Wnt1-high tumors, 72 MPMs (67.3%) were Wnt2B-high tumors and 54 MPMs (50.5%) were Wnt5A-high tumors. There was no correlation among the levels of Wnt expression. The percentage of Wnt2B-positive tumors was significantly higher compared to that of the other Wnts (p<0.0001). Furthermore, intratumoral Wnt2B expression significantly correlated with the expression of survivin (p<0.001) and c-Myc (p<0.001). Regarding tumor biology, the Ki-67 proliferation index was significantly higher in the Wnt2B-high tumors than in the Wnt2B-low tumors (p=0.0438). In addition, the overall survival was significantly lower in patients with Wnt2B-high tumors than in those with Wnt2B-low tumors (p=0.0238). A Cox multivariate analysis also demonstrated the Wnt2B status to be a significant prognostic factor in MPM patients (p=0.0042). Intratumoral Wnt2B expression was associated with the expression of survivin and c-Myc, tumor proliferation and patient survival in MPM. Wnt2B is a potential molecular target for the treatment of Wnt2B-overexpressing MPMs.