title: CAVEOLIN-1 expression in brain metastasis from lung cancer predicts worse outcome and radioresistance, irrespective of tumor histotype.
abstract: Brain metastases develop in one-third of patients with non-small-cell lung cancer and are associated with a dismal prognosis, irrespective of surgery or chemo-radiotherapy. Pathological markers for predicting outcomes after surgical resection and radiotherapy responsiveness are still lacking. Caveolin 1 has been associated with chemo- and radioresistance in various tumors, including non-small-cell lung cancer. Here, caveolin 1 expression was assessed in a series of 69 brain metastases from non-small-cell lung cancer and matched primary tumors to determine its role in predicting survival and radiotherapy responsiveness. Only caveolin 1 expression in brain metastasis was associated with poor prognosis and an increased risk of death (log rank test, p = 0.015). Moreover, in the younger patients (median age of <54 years), caveolin 1 expression neutralized the favorable effect of young age on survival compared with the older patients. Among the radiotherapy-treated patients, an increased risk of death was detected in the group with caveolin 1-positive brain metastasis (14 out of 22 patients, HR=6.839, 95% CI 1.849 to 25.301, Wald test p = 0.004). Overall, caveolin 1 expression in brain metastasis from non-small-cell lung cancer is independently predictive of worse outcome and radioresistance and could become an additional tool for personalized therapy in the critical subset of brain-metastatic non-small-cell lung cancer patients.
authors: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Turin, Italy.
authors: Eleonora
authors: E
authors: Duregon
authors: Department of Medical Sciences, University of Torino, Italy.
authors: Rebecca
authors: R
authors: Senetta
authors: Department of Medical Sciences, University of Torino, Italy.
authors: Alessandra
authors: A
authors: Pittaro
authors: Department of Medical Sciences, University of Torino, Italy.
authors: Ludovica
authors: L
authors: Verdun di Cantogno
authors: Laboratory of Biochemistry and Genetics, Pneumology Unit, Department of Molecular Medicine University and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors: Giulia
authors: G
authors: Stella
authors: University of Torino and Collegio Carlo Alberto, Torino, Italy.
authors: Pierpaolo
authors: P
authors: De Blasi
authors: Laboratory of Biochemistry and Genetics, Pneumology Unit, Department of Molecular Medicine University and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors: Michele
authors: M
authors: Zorzetto
authors: Department of Oncology, Radiation Oncology, University of Torino, Italy.
authors: Cristina
authors: C
authors: Mantovani
authors: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Turin, Italy.
authors: Mauro
authors: M
authors: Papotti
authors: Department of Medical Sciences, University of Torino, Italy.
authors: Paola
authors: P
authors: Cassoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D051242:Caveolin 1
keywords: brain metastasis; caveolin 1; non-small-cell lung cancer; radiotherapy