PMID- 20735841 OWN - NLM STAT- MEDLINE DCOM- 20110203 LR - 20211020 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 10 DP - 2010 Aug 24 TI - Molecular alterations in key-regulator genes among patients with T4 breast carcinoma. PG - 458 LID - 10.1186/1471-2407-10-458 [doi] AB - BACKGROUND: Prognostic factors in patients who are diagnosed with T4 breast carcinomas are widely awaited. We here evaluated the clinical role of some molecular alterations involved in tumorigenesis in a well-characterized cohort of T4 breast cancer patients with a long follow-up period. METHODS: A consecutive series of 53 patients with T4 breast carcinoma was enrolled between 1992 and 2001 in Sardinia, and observed up for a median of 125 months. Archival paraffin-embedded tissue sections were used for immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analyses, in order to assess alterations in expression levels of survivin, p53, and pERK1-2 proteins as well as in amplification of CyclinD1 and h-prune genes. The Kaplan-Meier and Cox regression methods were used for survival assessment and statistical analysis. RESULTS: Overall, patients carrying increased expression of pERK1-2 (p = 0.027) and survivin (p = 0.008) proteins as well as amplification of h-prune gene (p = 0.045) presented a statistically-significant poorer overall survival in comparison with cases found negative for such alterations. After multivariate analysis, the pathological response to primary chemotherapy and the survivin overexpression in primary carcinoma represented the main parameters with a role as independent prognostic factors in our series. CONCLUSIONS: Although retrospective, our study identified some molecular parameters with a significant impact on prediction of the response to therapy or prognosis among T4 breast cancer patients. Further large prospective studies are needed in order to validate the use of such markers for the management of these patients. FAU - Massidda, Bruno AU - Massidda B AD - Department of Medical Oncology, University of Cagliari, Cagliari, Italy. FAU - Sini, Mariacristina AU - Sini M FAU - Budroni, Mario AU - Budroni M FAU - Atzori, Francesco AU - Atzori F FAU - Deidda, Mariacristina AU - Deidda M FAU - Pusceddu, Valeria AU - Pusceddu V FAU - Perra, Mariateresa AU - Perra M FAU - Sirigu, Paola AU - Sirigu P FAU - Cossu, Antonio AU - Cossu A FAU - Palomba, Grazia AU - Palomba G FAU - Ionta, Mariateresa AU - Ionta M FAU - Palmieri, Giuseppe AU - Palmieri G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100824 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (BIRC5 protein, human) RN - 0 (Biomarkers, Tumor) RN - 0 (CCND1 protein, human) RN - 0 (Carrier Proteins) RN - 0 (Inhibitor of Apoptosis Proteins) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Survivin) RN - 0 (TP53 protein, human) RN - 0 (Tumor Suppressor Protein p53) RN - 136601-57-5 (Cyclin D1) RN - EC 2.7.11.24 (MAPK1 protein, human) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 3.1.3.2 (PRUNE1 protein, human) RN - EC 3.1.3.2 (Phosphoric Monoester Hydrolases) SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Biomarkers, Tumor/genetics/metabolism MH - Breast Neoplasms/drug therapy/*genetics/metabolism MH - Carrier Proteins/*genetics/metabolism MH - Cyclin D1/*genetics/metabolism MH - Female MH - Follow-Up Studies MH - Gene Amplification MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Immunoenzyme Techniques MH - In Situ Hybridization, Fluorescence MH - Inhibitor of Apoptosis Proteins MH - Italy MH - Microtubule-Associated Proteins/*genetics/metabolism MH - Middle Aged MH - Mitogen-Activated Protein Kinase 1/*genetics/metabolism MH - Mitogen-Activated Protein Kinase 3/*genetics/metabolism MH - Neoplasm Staging MH - Phosphoric Monoester Hydrolases MH - Retrospective Studies MH - Survival Rate MH - Survivin MH - Treatment Outcome MH - Tumor Suppressor Protein p53/*genetics/metabolism PMC - PMC2936331 EDAT- 2010/08/26 06:00 MHDA- 2011/02/04 06:00 PMCR- 2010/08/24 CRDT- 2010/08/26 06:00 PHST- 2010/03/05 00:00 [received] PHST- 2010/08/24 00:00 [accepted] PHST- 2010/08/26 06:00 [entrez] PHST- 2010/08/26 06:00 [pubmed] PHST- 2011/02/04 06:00 [medline] PHST- 2010/08/24 00:00 [pmc-release] AID - 1471-2407-10-458 [pii] AID - 10.1186/1471-2407-10-458 [doi] PST - epublish SO - BMC Cancer. 2010 Aug 24;10:458. doi: 10.1186/1471-2407-10-458.