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.

Keywords: brain metastasis; caveolin 1; non-small-cell lung cancer; radiotherapy.

Figure 1. Representative examples of two brain metastasis from lung adenocarcinoma (A, C hematoxylin & Eosin, original magnification 400X) with mild to strong membrane-cytoplasmic immunoreactivity and negative staining for Cav1 (respectively B, D original magnification 400X) and high CAV1 gene polysomy by FISH analysis (E)

Figure 2. Survival curves showing that grouping by histotype was not a significant predictor for survival (Log rank test, p=0.233, 2A)

Conversely, adenocarcinoma was associated with prolonged survival when other histotypes were considered together (Log rank test, p=0.056, 2B).

Figure 3. Survival curves demonstrating the association between Cav1 expression in brain metastasis and poor prognosis (Log rank test, p=0.015)