Evaluation of gene amplification and protein expression of HER-2/neu in esophageal squamous cell carcinoma using Fluorescence in situ Hybridization (FISH) and immunohistochemistry.
Evaluation of gene amplification and protein expression of HER-2/neu in esophageal squamous cell carcinoma using Fluorescence in situ Hybridization (FISH) and immunohistochemistry.
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DOI：
10.1186/1471-2407-9-6
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发表时间：
2009-01-07
期刊：
影响因子：
3.8
通讯作者：
Soares FA
中科院分区：
文献类型：
--
作者：
Sato-Kuwabara Y;Neves JI;Fregnani JH;Sallum RA;Soares FA
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. 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 ≥ 2 were considered positive for gene amplification. 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. 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.
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影响因子：
9
作者：
FUJITA, H;KAKEGAWA, T;MIZUTANI, K
通讯作者：
MIZUTANI, K
影响因子：
6.4
作者：
Mayr, D;Kanitz, V;Diebold, J
通讯作者：
Diebold, J
DOI：
10.1016/s0748-7983(97)80139-4
发表时间：
1997-02-01
期刊：
EUROPEAN JOURNAL OF SURGICAL ONCOLOGY
影响因子：
--
作者：
Hardwick, RH;Barham, CP;Alderson, D
通讯作者：
Alderson, D
影响因子：
4.7
作者：
Lassus, Heini;Sihto, Harri;Butzow, Ralf
通讯作者：
Butzow, Ralf
DOI：
10.1007/bf02717000
发表时间：
2005-12-01
期刊：
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
影响因子：
--
作者：
Gebhart, Erich
通讯作者：
Gebhart, Erich