mTOR Immunohistochemical Expression Is of Prognostic Relevance in High Risk Breast Carcinoma
E Bragantini, F Mauri, C Cantaloni, D Aldovini, M Bonzanini, A Ferro, E Galligioni, F Buttitta, A Marchetti, L Cuorvo, P Dalla Palma, M Barbareschi. S. Chiara Hospital, Trento, Italy; Imperial College London, Hammersmith Hospitals, London, United Kingdom; University Gabriele D'Annunzio, Chieti, Italy
Background: The PI3K/AKT/mTor pathway is of pivotal relevance in breast cancer. Its alterations may be of prognostic/predictive value. mTOR is a protein kinase of the PI3K/AKT signalling pathway and central role in controlling cancer cellular growth and cell cycle progression . The mTOR pathway is abnormally actived in many tumors and could be a target for specific therapy. Sirolimus and its analogues Temsirolimus, Everolimus, and Deforolimus are specific small molecule inhibitors of mTOR and some of these agents are now being examined as novel therapies for cancer.
Design: We evaluated a series of 165 consecutive infiltrating breast carcinomas with long term follow-up (median f-up: 85 months). The clinico-pathological characteristics of the series were: 80 T1, 63T2, 22 T3/4, 12 G1, 75 G2, 68 G3, 5 Gx, 76 N0, 85N1, 4 Nx. Cases were grouped according to St. Gallen risk categories in low (4 cases), intermediate (97 cases) and high (48 cases) risk (for 19 cases risk category was not asssable). All cases had been studied for ER, PgR, Her2, p53 and MIB1 immunohistochemical expression and for PI3K and AKT mutations (as previously shown Clin Cancer Res. 2008; 14(6):1726) All cases were included in tissue microarrays, and immunostained for PTEN and mTOR. PTEN and mTOR immunoreactivity were scored as low to absent (score 0-1) and strong (score 2) on a semiquantitative basis. Follow-up data and therapy were recorded for all cases.
Results: mTOR expression were not related to any pathological parameter nor with ER, PgR, p53 and Her2 status nor with PTEN, PI3K and AKT alterations. Survival analysis showed that high mTOR expression was related with prolonged overall and relapse free survival in several groups of patients, including node positive, chemotherapy treated patients and in high risk subgroups.
Conclusions: Our results suggest that high risk breast cancer patients who are mTOR positive might have prolonged survival and further studies are required to evaluate if mTOR expression could be of relevance in the selection of patients who could be candidates for mTOR inhibition therapy.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 65, Tuesday Morning