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Much evidence has accumulated that the epidermal growth factor receptor (EGFR) and its family members are strongly implicated in the development and progression of lung cancers. Recently, erbB4 kinase domain mutations were reported in Korean patients with lung cancer. We hypothesized that erbB4 mutations correlate with clinicopathologic features of lung cancers.The presence or absence of erbB4 kinase domain mutations was analyzed by reverse-transcription polymerase chain reaction amplification and direct sequencing in 105 surgically treated non-small-cell lung cancer cases from Nagoya City University Hospital. Sixty-three adenocarcinoma cases were included. The EGFR mutation status for these 105 samples were already reported. We have investigated erbB4 expression status by immunohistochemistry in 40 non-small cell lung cancer cases.ErbB4 mutation was not found in 105 patients with lung cancer. The EGFR mutation status was significantly correlated with sex (women, 74.2% vs. men, 9.5%; P0.0001), smoking status (never-smokers, 68.8% vs. smokers, 11%; P0.0001), pathologic subtype (adenocarcinoma, 44.4% vs. non-adenocarcinoma, 4.8%; P0.0001), and differentiation status of the lung cancer (well-differentiated, 47.4% vs. others, 14.8%; P = 0.0004). We detected ErbB4 protein positivity in 20 samples. The ErbB4 protein status was not significantly correlated with sex (women, 28.6% vs. men, 54.5%; P = 0.4075), smoking status (never-smokers, 69.4% vs. smokers, 16.9%; P0.0001), pathologic subtype (adenocarcinoma, 46.2% vs. nonadenocarcinoma, 51.9%; P0.9999), or differentiation status of the lung cancer (well-differentiated, 54.5% vs. others, 48.3%; P0.9999).Thus, erbB4 mutations are rare in Japanese people with lung cancer and of limited value for molecular-targeted therapy.

Purpose Human MOB1 ( hMOB1 ) is a recently isolated gene that is a human homologue of the Schizosaccharomyces mitotic checkpoint gene MOB1 . The loss of checkpoint control in mammalian cells results in genomic instability, leading to the amplification, rearrangement, or loss of chromosomes, events associated with tumor progression. We hypothesized that hMOB1 might be expressed in non–small-cell lung cancer (NSCLC). Patients and Methods We attempted to determine the influence of hMOB1 expression on clinicopathologic features in patients with NSCLC who had undergone surgery. Expression of hMOB1 messenger RNA (mRNA) was evaluated by reverse transcription-polymerase chain reaction in 60 NSCLCs and adjacent histologic normal lung samples using LightCycler®. Results Human MOB1/glyseraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression was significantly decreased in the tumor of lung cancer tissue (3.347 ± 4.306) compared with normal lung tissue (4.833 ± 4.306; P = 0.0437), although 22 of 60 lung cancer tissue samples had > 1 tumor-normal ratio of MOB1/GAPDH mRNA expression. There was no relationship between hMOB1 gene expression and age, sex, pathologic stages, or pN status. However, decreased hMOB1/GAPDH expression was especially seen in pT1 lung cancer (tumor-normal ratio; 0.318 ± 0.328) when compared with pT4 lung cancer (1.915 ± 1.895; P = 0.0362). Conclusion The decreased expression of hMOB1 mRNA might be the early phase phenomenon for tumor invasion from NSCLC. Alternatively, loss of mitotic checkpoint might play a role in oncogenesis for lung cancer.

Human kallikrein 11 (hK11) is a putative serine protease of the human kallikrein gene family. A recently developed method for measuring hK11 suggested that the hK11 level was an indicator of favorable prognosis in patients with ovarian cancer. We have investigated hK11 messenger RNA (mRNA) levels in lung cancer.This study included 64 lung cancer cases. The hK11 mRNA levels were quantified by real-time reverse-transcriptase polymerase chain reaction using LightCycler.The hK11 mRNA levels were lower in tumor tissues from lung cancer (1.88 +/- 6.314) compared with adjacent nonmalignant lung tissues (8.271 +/- 9.002; n = 45; P = 0.0001). No significant difference was found among sex, age, clinical stages, tumor status, and lymph node metastasis. The hK11 mRNA levels were lower in moderately or poorly differentiated adenocarcinoma lung cancer (0.452 +/- 1.614) compared with well-differentiated adenocarcinoma lung cancer (1.728 +/- 2.829; P = 0.0281). The group with low hK11/gylceraldehyde 3-phosphate dehydrogenase levels (0.6) had a significantly worse prognosis compared with the group with high hK11/gylceraldehyde 3-phosphate dehydrogenase levels (0.6; log-rank test, P = 0.0131; Breslow-Gehan-Wilcoxon test, P = 0.0172).Cox proportional hazard regression model (multivariate analysis) indicated that pathologic stages (P = 0.0443) and low hK11 expression levels (P = 0.0469) were the prognostic factors of lung cancers. However, additional studies and a longer follow-up are needed to confirm the impact of hK11 on the biologic behavior of the tumor.