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Periostin is an extracellular matrix N-glycoprotein that is a major constituent of the desmoplastic stroma around solid tumors. Periostin promotes tumor invasion and metastasis via epithelial-mesenchymal transition. The aims of this study were to evaluate periostin expression immunohistochemically and quantitatively in patients with non-small cell lung cancer (NSCLC) and to assess any associations with clinical features and prognosis. A total of 184 specimens of NSCLC tissue were investigated, including 134 adenocarcinomas, 39 squamous cell carcinomas, and 11 other histologic subtypes. The intra-tumoral periostin expression area in each captured field was calculated using the image processing integration software WinROOF. The mean periostin expression score was classified as high or low by the median value of its expression area. Univariate analysis demonstrated that gender, tumor size, T status, N status, stage, histologic type, smoking habits, percent vital capacity, 1% forced expiratory volume, and pleural invasion were each significantly associated with periostin scores. Multivariate analysis revealed that high periostin expression score was an independent prognostic factor significantly associated with decreased cancer-specific survival (HR, 3.65; 95% CI, 1.04-12.84; P=0.0439). We concluded that intratumoral periostin expression was an independent prognostic factor for NSCLC.

Purpose: Therapeutic responses of non-small cell lung carcinoma (NSCLC) to epidermal growth factor receptor (EGFR)-targeted drugs, such as gefitinib and erlotinib, are closely associated with activating EGFR mutations. The most common mutations are delE746-A750 in exon 19 and L858R in exon 21, accounting for approximately 90% of all EGFR mutations. Recently, EGFR mutation-specific antibodies were developed and did well in immunohistochemical analysis, giving a sensitivity of approximately 90%. We have investigated whether this method detects activating EGFR mutations with sensitivity comparable with direct DNA sequencing, which is used to detect these mutations in NSCLC., Experimental Design: We used antibodies specific for the E746-A750 deletion mutation in exon 19 and the L858R point mutation in exon 21 in Western blot analysis and immunohistochemistry to determine the presence of these mutations in NSCLC cell lines. We also examined these EGFR mutations in NSCLC tumor samples from 60 patients by immunohistochemically and direct DNA sequencing., Results: We were able to identify EGFR mutations in NSCLC tumor samples immunohistochemically with a sensitivity of 79% using the anti-delE746-A750 antibody and 83% using the anti-L858R antibody. Additional DNA sequencing markedly improved the sensitivity obtained by immunohistochemistry., Conclusions: This simple and rapid assay for detecting EGFR mutations, even in the small bronchial biopsies obtained in stage IV NSCLC patients, will be useful for diagnosing responsiveness to EGFR-targeted drugs in patients with NSCLC. Combining this with DNA sequencing is recommended for the development of improved personalized EGFR-targeted therapeutics., ((c) 2010 AACR.)

Introduction: Nuclear expression of Y-box binding protein-1 (YB-1) is closely associated not only with global drug resistance and expression of several growth factor receptors in various human malignancies but also with overall patient survival., Methods: The effect of YB-1 knockdown on expression of epidermal growth factor receptor (EGFR) family proteins was examined by Western blot using human lung cancer cell lines. Immunohistochemistry was used to evaluate the expression of nuclear YB-1 and EGFR family proteins in patients with non-small cell lung cancer (NSCLC) (n = 104)., Results: In the five NSCLC cell lines, expressions of EGFR, human epidermal growth factor receptor 2 (HER2), HER3, and hepatocyte growth factor receptor (c-Met) in PC-9 cells; of HER2 and c-Met in EBC-1 cells; and of HER3 in QG56 cells were down-regulated by YB-1 knockdown. By immunohistochemical analysis, we observed that HER3 expression was significantly negatively correlated with nuclear YB-1 expression in squamous cell carcinoma (p = 0.038). HER2 expression was positively correlated with nuclear YB-1 expression in adenocarcinoma (p = 0.052). Nuclear expression of YB-1 correlated with overall survival of all patients (p = 0.028) and of patients with adenocarcinoma (p = 0.007). Furthermore, there was a significant difference in therapeutic efficacies of gefitinib between patients with nuclear YB-1 expression and those with non-nuclear YB-1 expression in patients with NSCLC (p = 0.004, n = 26) but not between those with high and those with low expression of EGFR, HER2, HER3, and c-Met., Conclusion: Nuclear YB-1 expression might be essential for the malignant phenotype in lung cancer patients and might be an important biomarker for the development of therapeutic strategy against NSCLC.