Valutazione della clonalità genica del carcinoma della mammella e suo impatto sulla risposta terapeutica

Breast cancer is about 30% of female cancers and about 1% of males. The evaluation of Her 2 is of primary importance in breast cancer, because it is linked to a target therapy. Despite updated guidelines, the impact of HER2 heterogeneous cell populations on the disease progression remains unclear. In the first study we evaluated Her2 heterogeneity by FISH (fluorescence in situ hybridization) using 3 cut-off (30% -20% -10%), correlating to the presence of recurrences and metastases. We then compared an homogeneous population of 109 cases with a heterogeneous population similar for age of the patients, stage and grade of the tumours. From the data obtained we observe that an unamplified subpopulation (? 20%) is a favorable prognostic factor in FISH positive cases; on the contrary, in FISH negative cases, the detectiong an amplified cells population is indicative of a more aggressive behavior of the disease. Male breast cancer is a poorly known disease due to its very low incidence rate, that increases (up o 25%) in patients with Klinefelter' sydrome (47XXY). Therefore we evaluated the presence of X chromosome aneusomy in 20 male breast cancer cases compared to 10 cases of gynecomastia and to the healthy skin tissue. Data obtained showed that all the male breast cancers presented X chromosome aneusomy in > 20% of the neoplastic cells. Therefore we can hypothyse the role of X in the early stages of cancer; further investigations are in progress. From a technical perspective, we compared 26 difficult cases analyzing them with standard immunohistochemistry (IHC) and FISH compared to the new double staining IHC and SISH (silver in situ hybridization) observing a significant diagnostic concordance between the methods. Finally we have developed and filed a patent application about a method able to reduce to just over 2 hours the FISH technical time.