RESUMO
BACKGROUND: We have reported promising results of surgery after induction chemoradiotherapy (carboplatin-taxane, 50 Gy radiation) for cN2,3 non-small cell lung cancer (NSCLC). In order to understand the underlying mechanism, expression of excision repair cross-complementing 1 (ERCC1), class III ß-tubulin (tubulin), thymidylate synthase (TYMS), and ribonucleotide reductase M1 (RRM1) were investigated. PATIENTS AND METHODS: Immunohistochemistry was performed in 45 patients with cN2,3 NSCLC, but only in twelve pathologically-complete response cases to evaluate intratumoral expression of these biomarkers. RESULTS: High expression of ERCC1, tubulin, TYMS and RRM1 was observed in 25 (55.6%), 19 (42.2%), 20 (44.4%) and 25 (55.6%) patients, respectively. Low expressions of ERCC1, tubulin, TYMS and RRM1 were favorable prognostic factors (p=0.044, p=0.025, p=0.039 and p=0.037, respectively). The simultaneously low expression of ERCC1 and tubulin was observed to be the most significant prognostic factor, by Cox regression analysis (hazard ratio=2.381; p=0.0059). CONCLUSION: Patients with simultaneous low expression of ERCC1 and tubulin are promising candidates for surgery after carboplatin-taxane chemoradiotherapy. For patients with high expression of ERCC1 and tubulin, uracil-tegafur, pemetrexed, and gemcitabine may be the alternative agents for personalized chemotherapy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Neoplasias Pulmonares/terapia , Idoso , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/química , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Proteínas de Ligação a DNA/análise , Endonucleases/análise , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/química , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Ribonucleosídeo Difosfato Redutase , Timidilato Sintase/análise , Tubulina (Proteína)/análise , Proteínas Supressoras de Tumor/análiseRESUMO
BACKGROUND: Matrix metalloporteinase-7 (MMP-7) is a member of the MMP family, and it has been reported to play an important role in tumorigenesis, invasion and metastasis. We performed a retrospective study on the MMP-7 expression in non-small cell lung cancer (NSCLC) according to the clinical characteristics, biological markers and the Wnt1 expression. PATIENTS AND METHODS: One hundred forty-seven postsurgical NSCLC patients were investigated. Immunohistochemistry was performed to evaluate the MMP-7 expression, the Ki-67 proliferation index, tumor angiogenesis and the Wnt1 expression. The TUNEL method was performed to investigate tumor apoptosis. RESULTS: Seventy-six carcinomas (51.7%) were MMP-7-positive. The MMP-7 expression was significantly higher in squamous cell carcinomas than in adenocarcinomas (P<0.0001). The Ki-67 proliferation index was significantly higher in MMP-7-positvie tumors than in MMP-7-negative tumors (P=0.0003). However, there was no difference in the MMP-7 expression in relation to apoptosis or angiogenesis. Regarding its regulation, the MMP-7 expression significantly correlated with the Wnt1 expression (r=0.426, P<0.0001). The overall survival was significantly lower in patients with MMP-7-positive NSCLCs than in those with MMP-7-negative NSCLCs (P=0.0018). A Cox regression analyses also demonstrated MMP-7 status to be a significant prognostic factor (hazard ratio, 2.187; P=0.0023). CONCLUSIONS: The overexpression of MMP-7 was associated with tumor proliferation, and a poor prognosis in NSCLCs. In addition, Wnt1 may play a critical role in regulating the intratumoral MMP-7 expression.
