CAVEOLIN-1 expression in brain metastasis from lung cancer predicts worse outcome and radioresistance, irrespective of tumor histotype
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Eleonora Duregon1,*, Rebecca Senetta5,*, Alessandra Pittaro5, Ludovica Verdun di Cantogno5, Giulia Stella2, Pierpaolo De Blasi3, Michele Zorzetto2, Cristina Mantovani4, Mauro Papotti1 and Paola Cassoni5
1 Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Turin, Italy
2 Laboratory of Biochemistry and Genetics, Pneumology Unit, Department of Molecular Medicine University and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
3 University of Torino and Collegio Carlo Alberto, Torino, Italy
4 Department of Oncology, Radiation Oncology, University of Torino, Italy
5 Department of Medical Sciences, University of Torino, Italy
* These authors have contributed equally to this work
Paola Cassoni, email:
Keywords: Caveolin 1, brain metastasis, non-small-cell lung cancer, radiotherapy
Received: April 10, 2015 Accepted: July 16, 2015 Published: July 22, 2015
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.
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