Caveolin-1 Expression Predicts Outcome in Oligodendroglial Tumours Regardless of 1p/19q Status
L Molinaro, R Senetta, E Maldi, V Crudo, M Lanotte, L Chiusa, R Soffietti, P Cassoni. University of Turin, Turin, Italy
Background: Caveolin-1 (Cav-1) is the basic component of caveole, omega-shaped membrane microdomains involved in various cell functions. In tumours, Cav-1 can be either overexpressed, suggesting a pro-neoplastic role, or downregulated: therefore, its role in oncogenesis is still debated. Regarding brain tumours, our group demonstrated that Cav-1 is significantly more expressed in astrocytic-derived tumours than in oligodendrogliomas, suggesting how this marker could be used as a valuable tool in the differential diagnosis between these two categories. Moreover, in tumours of astrocytic origin, we reported that Cav-1 expression increases accordingly to tumour grade, thus suggesting a tumour-aggressiveness related phenotype and envisaging a possible role for Cav-1 in predicting patients' prognosis.
Design: We here studied Cav-1 expression in oligodendroglial tumours, such as oligodendrogliomas (OD), oligoastrocyromas (OA) and glioblastomas with oligodendroglial component (GBMO) to evaluate its potential role as a prognostic factor and to determine if its expression is related to 1p/19 deletion, to date the hallmark prognostic factor for these gliomas. Eighty-seven cases of ODs, OAs and GBMOs were collected, and studied for 1p/19q status and Cav-1 expression by FISH analysis and immunohistochemistry respectively.
Results: Cav-1 was expressed in a minority of cases (21.8%), mostly grade III OAs and GBMO; 1p/19q deletion was expressed in 45,97% cases, mostly grade II and III ODs. The correlation between 1p/19q deletion and loss of Cav-1 staining was proven to be statistically significative (p= 0.0002), as well as a single chromosome deletion (1p or 19q), defining a group of patients with better prognosis. Moreover, Cav-1 positivity independently recognized a subset of tumours with worse prognosis (Mantel-Cox=0.03), even if concurrently carrying 1p and/or 19q deletion.
Conclusions: We here provide the first evidence that Cav-1 is a new trustworthy, easy to manage, independent prognostic marker in oligodendroglial-derived tumours regardless of the 1p/19q status Since Cav-1 has been also associated with mechanisms underlying multi-drug resistance, we feel thus entitled to preliminarily suggest that the worse outcome in Caveolin-1 positive patients in our series could be at least partially related to an acquired chemotherapy resistance.
Monday, March 9, 2009 1:45 PM
Platform Session: Section H, Monday Afternoon