title: Clinical application of biological markers for treatments of resectable non-small-cell lung cancers.
abstract: We performed a clinical study to identify biological markers useful for the treatment of resectable non-small-cell lung cancers (NSCLCs). In all, 173 patients were studied. By immunohistochemistry, we evaluated the Ki-67 proliferation index, tumour vascularity, thymidylate synthase (TS), vascular endothelial growth factor (VEGF)-A, VEGF-C, and E (epithelial)-cadherin. Concerning the survival of NSCLC patients, tumour vascularity (P<0.01), VEGF-A status (P=0.03), VEGF-C status (P=0.03), and E-cadherin status (P=0.03) were significant prognostic factors in patients with stage I NSCLCs. The Ki-67 proliferation index (P=0.02) and TS status (P<0.01) were significant prognostic factors in patients with stage II-III NSCLCs. In patients with stage II-III NSCLCs, furthermore, the survival of UFT (a combination of tegafur and uracil)-treated patients with TS-negative tumours was significantly better than those of any other patients. Biological markers associated with tumour angiogenesis or metastasis are useful for the detection of aggressive tumours among early-stage NSCLCs. Postoperative chemotherapy might be necessary in such tumours even in stage I. In contrast, tumour proliferation rate and TS status are useful markers for identifying less aggressive tumours in locally advanced NSCLCs. Thymidylate synthase expression is also a useful marker to evaluate responsiveness of UFT-based chemotherapy for these tumours.
authors.affiliation: Second Department Surgery, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. chuang@kms.ac.jp
authors.forename: C
authors.initials: C
authors.lastname: Huang
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Masuya
authors.forename: T
authors.initials: T
authors.lastname: Nakashima
authors.forename: K
authors.initials: K
authors.lastname: Kameyama
authors.forename: S
authors.initials: S
authors.lastname: Ishikawa
authors.forename: M
authors.initials: M
authors.lastname: Ueno
authors.forename: R
authors.initials: R
authors.lastname: Haba
authors.forename: H
authors.initials: H
authors.lastname: Yokomise
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology* / Q000601:surgery; D049109:Cell Proliferation; D005260:Female; D006133:Growth Substances / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D009389:Neovascularization, Pathologic; D010347:Patient Care Planning; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013940:Thymidylate Synthase / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D006133:Growth Substances; D019394:Ki-67 Antigen; D013940:Thymidylate Synthase