PMID- 19128465 OWN - NLM STAT- MEDLINE DCOM- 20090324 LR - 20211020 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 9 DP - 2009 Jan 7 TI - Evaluation of gene amplification and protein expression of HER-2/neu in esophageal squamous cell carcinoma using Fluorescence in situ Hybridization (FISH) and immunohistochemistry. PG - 6 LID - 10.1186/1471-2407-9-6 [doi] AB - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the sixth most frequent neoplasia in Brazil. It is usually associated with a poor prognosis because it is often at an advanced stage when diagnosed and there is a high frequency of lymph node metastases. It is important to know what prognostic factors can facilitate diagnosis, optimize therapeutic decisions, and improve the survival of these patients. A member of the epidermal growth factor receptor (EGFR) family, c-erbB-2, has received much attention because of its therapeutic implications; however, few studies involving fluorescence in situ hybridization (FISH) analysis of HER-2/neu gene amplification and protein expression in ESCC have been conducted. The aim of this study was to verify the presence of HER-2/neu gene amplification using FISH, and to correlate the results with immunohistochemical expression and clinical-pathological findings. METHODS: One hundred and ninety-nine ESCC cases were evaluated using the Tissue Microarray (TMA) technique. A polyclonal antibody against c-erbB-2 was used for immunohistochemistry. Analyses were based on the membrane staining pattern. The results were classified according to the Herceptest criteria (DAKO): negative (0/1+), potential positive (2+) and positive (3+). The FISH reactions were performed according to the FISH HER2 PharmDx (DAKO) protocol. In each case, 100 tumor nuclei were evaluated. Cases showing a gene/CEN17 fluorescence ratio > or = 2 were considered positive for gene amplification. RESULTS: The c-erbB-2 expression was negative in 117/185 cases (63.2%) and positive in 68 (36.8%), of which 56 (30.3%) were 2+ and 12 (6.5%) were 3+. No significant associations were found among protein expression, clinicopathological data and overall survival. Among the 47 cases analyzed, 38 (80.9%) showed no gene amplification while 9 (19.1%) showed amplification, as demonstrated by FISH. Cases that were negative (0/1+) and potential positive (2+) for c-erbB-2 expression by immunohistochemistry showed no gene amplification. However, all cases with gene amplification were positive (3+) by immunohistochemistry. According to univariate analysis, there was a significant difference (p = 0.003) in survival rates when cases with and without HER-2/neu amplification were compared. CONCLUSION: Our data demonstrate the correspondence between gene amplification and protein expression of HER-2/neu. Gene amplification is an indicator of poor prognosis in ESCC. FAU - Sato-Kuwabara, Yukie AU - Sato-Kuwabara Y AD - Department of Anatomic Pathology, Hospital AC Camargo, Sao Paulo, SP, Brazil. yukiesato@gmail.com FAU - Neves, Jose I AU - Neves JI FAU - Fregnani, Jose H T G AU - Fregnani JH FAU - Sallum, Rubens A AU - Sallum RA FAU - Soares, Fernando A AU - Soares FA LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090107 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Squamous Cell/diagnosis/*genetics/metabolism/mortality MH - Esophageal Neoplasms/diagnosis/*genetics/metabolism/mortality MH - Female MH - *Gene Amplification MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Prognosis MH - Receptor, ErbB-2/*genetics/*metabolism MH - Survival Rate PMC - PMC2648997 EDAT- 2009/01/09 09:00 MHDA- 2009/03/25 09:00 PMCR- 2009/01/07 CRDT- 2009/01/09 09:00 PHST- 2008/03/12 00:00 [received] PHST- 2009/01/07 00:00 [accepted] PHST- 2009/01/09 09:00 [entrez] PHST- 2009/01/09 09:00 [pubmed] PHST- 2009/03/25 09:00 [medline] PHST- 2009/01/07 00:00 [pmc-release] AID - 1471-2407-9-6 [pii] AID - 10.1186/1471-2407-9-6 [doi] PST - epublish SO - BMC Cancer. 2009 Jan 7;9:6. doi: 10.1186/1471-2407-9-6.