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Purpose: Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in f25% of Japanese lung cancer patients. These EGFR mutations are reported to be correlated with clinical response to gefitinib therapy. However, DNA sequencing using the PCR methods described to date is time-consuming and requires significant quantities of DNA; thus, this existing approach is not suitable for a routine pretherapeutic screening program. Experimental Design: We have genotyped EGFR mutation status in Japanese lung cancer patients, including 102 surgically treated lung cancer cases from Nagoya City University Hospital and 16 gefitinib-treated lung cancer cases from Kinki-chuo Chest Medical Center. The presence or absence of three common EGFR mutations were analyzed by real-time quantitative PCR with mutation-specific sensor and anchor probes. Results: In exon 21, EGFR mutations (CTG ! CGG; L858R) were found from 8 of 102 patients from Nagoya and 1of 16 from Kinki.We also detected the deletion mutations in exon 19 from 7 of 102 patients from Nagoya (all were deletion type1a) and 4 of16 patients from Kinki (one was type 1a and three were type 1b). In exon 18, one example of G719S mutation was found from both Nagoya and Kinki. The L858R mutation was significantly correlated with gender (women versus men, P < 0.0001), Brinkman index (600 Q versus 600>, P = 0.001), pathologic subtypes (adenocarcinoma versus nonadenocarcinoma, P = 0.007), and differentiation status of the lung cancers (well versus moderately or poorly, P = 0.0439), whereas the deletion mutants were not. EGFR gene status, including the type of EGFR somatic mutation, was correlated with sensitivity to gefitinib therapy. For example, some of our gefitinib-responsive patients had L858R or deletion type1a mutations. On the other hand, one of our gefitinib-resistant patients had a G719S mutation. Conclusions: Using the LightCycler PCR assay, the EGFR L858R mutation status might correlate with gender, pathologic subtypes, and gefitinib sensitivity of lung cancers. However, further genotyping studies are needed to confirm the mechanisms of EGFR mutations for the sensitivity or resistance of gefitinib therapy for the lung cancer.

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We used our palindromic polymerase chain reaction (PCR)-driven cDNA differential display technique to identify and isolate a gene, designated periostin, from cancer tissues and found it to be overexpressed in several human tumors. We attempted to determine the influence of periostin expression on clinical outcome in patients with non-small cell lung cancer (NSCLC) by reverse transcriptase (RT)-PCR analysis. Periostin gene was highly expressed at the tumor periphery of lung cancer tissue but not within the tumor by in situ RNA hybridization, suggesting that expression of periostin may be involved in the process of tumor invasion. Periostin transcripts were detected in 50 (49.0%) of the tumor samples, although some paired normal lung samples showed weak expression. There was no relationship between periostin gene expression and gender, N-or Tstatus. The NSCLC patients with periostin expression had significantly poorer survival than the patients without periostin expression (P = = = =0.0338). Key words: Periostin-RT-PCR-Lung cancer-PrognosisLung cancer is a major cause of death from malignant diseases, due to its high incidence and malignant behavior, and the lack of major advances in treatment strategy. 1)Lung cancer was the leading indication for respiratory surgery (42.2%) in 1998 in Japan, with more than 15 000 patients undergoing surgical operation at Japanese institutions.2) The clinical behavior of non-small lung cancer (NSCLC) is largely associated with its stage.3) However, a significant number of tumors in patients with early-stage NSCLC show aggressive behavior and a tendency to relapse. Moreover, the prognosis for patients with operable NSCLC remains gloomy in comparison with that observed in operable gastric, colon, or breast cancer.4) A variety of clinicopathologic characteristics may affect prognosis. 5)Despite steadily accumulating evidence that numerous genetic markers influence the biological behavior of NSCLC, the intrinsic nature of the gene deregulation that leads small tumors to metastasize remains highly elusive. 6)The abnormal expression of certain genes in cancer cells is closely related to various aspects of tumor progression, including tumor growth, invasion and metastasis. Recently, we used the palindromic polymerase chain reaction (PCR)-driven cDNA differential display technique developed in our laboratory 7) to identify and isolate periostin cDNA, and found it to be overexpressed in several human tumors including primary colon cancer, metastatic liver cancer from colon cancer and breast cancer (Bao et al., manuscript in preparation). The periostin protein shares structural and sequence homology with fasciclin I, which is an insect adhesion molecule.8-10) It was reported that cellular adhesion molecules play an important role in the process of metastasis. 11)As available prognostic markers leave much to be desired for NSCLC, we investigated periostin transcript in patients with NSCLC by means of a reverse transcriptase PCR (RT-PCR) and in situ hybridization analysis, and we assessed t...