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Erschienen in: Journal of Cancer Research and Clinical Oncology 10/2009

01.10.2009 | Original Paper

Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance

verfasst von: Guan Zhen Yu, Ying Chen, Jie Jun Wang

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 10/2009

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Abstract

Purpose

Growth factor receptor-bound 2 (Grb2)-mediated HER2 signaling is thought to play a critical role in gastric cancer development, progression and metastasis. However, little is known about their expression in gastric cancer. In this study, we try to explore their relationship with clinicopathological parameters and prognostic significance in gastric cancer patients.

Materials and methods

We examined the expression of Grb2 and HER2 in normal gastric mucosa, primary gastric cancers, and lymph node metastases using immunohistochemical analysis of tissue microarrays containing specimens obtained from 1,143 patients with gastric cancer.

Results

Grb2 was overexpressed in 48% (553/1,143) of primary tumors and 59% (155/262) of lymph node metastases. We observed significant differences in Grb2 expression between the primary tumors and the lymph node metastases (P < 0.01). Also, HER2 was overexpressed in 28% (321/1,143) of the primary tumors and 30% (79/262) of the lymph node metastases. Overexpression of Grb2 and Her2 was associated with age (>60 years), tumor location (cardia of stomach), adenocarcinoma, and high/moderate differentiation. A significant relationship was found between Grb2 and HER2 expression using Chi-Square Tests and Spearman Correlation. Overexpression of Grb2 correlated significantly with poor survival rates in both univariate and multivariate analysis.

Conclusions

Our data demonstrated a progressive amplification of Grb2 and HER2 expression in gastric carcinogenesis, suggesting the importance of Grb2 and HER2 as positive biomarkers for gastric cancer development and progression.
Literatur
Zurück zum Zitat D’Ambrosio C, Hongo A, Li S et al (1996) The role of Grb2 in the growth and transformation of mouse embryo cells. Oncogene 12:371–378PubMed D’Ambrosio C, Hongo A, Li S et al (1996) The role of Grb2 in the growth and transformation of mouse embryo cells. Oncogene 12:371–378PubMed
Zurück zum Zitat Ghaderi A, Vasei M, Maleck-Hosseini SA et al (2002) The expression of c-erbB-1 and c-erbB-2 in Iranian patients with gastric carcinoma. Pathol Oncol Res 8:252–256CrossRefPubMed Ghaderi A, Vasei M, Maleck-Hosseini SA et al (2002) The expression of c-erbB-1 and c-erbB-2 in Iranian patients with gastric carcinoma. Pathol Oncol Res 8:252–256CrossRefPubMed
Zurück zum Zitat Half E, Broaddus R, Danenberg KD et al (2004) HER-2 receptor expression, localization, and activation in colorectal cancer cell lines and human tumors. Int J Cancer 108:540–548. doi:10.1002/ijc.11599 CrossRefPubMed Half E, Broaddus R, Danenberg KD et al (2004) HER-2 receptor expression, localization, and activation in colorectal cancer cell lines and human tumors. Int J Cancer 108:540–548. doi:10.​1002/​ijc.​11599 CrossRefPubMed
Zurück zum Zitat Janes PW, Daly RJ, deFazio A et al (1994) Activation of the Ras signalling pathway in human breast cancer cells overexpressing erbB-2. Oncogene 9:3601–3608PubMed Janes PW, Daly RJ, deFazio A et al (1994) Activation of the Ras signalling pathway in human breast cancer cells overexpressing erbB-2. Oncogene 9:3601–3608PubMed
Zurück zum Zitat Leng J, Lang J, Shen K et al (1997) Overexpression of p53, EGFR, c-erbB2 and c-erbB3 in endometrioid carcinoma of the ovary. Chin Med Sci J 12:67–70PubMed Leng J, Lang J, Shen K et al (1997) Overexpression of p53, EGFR, c-erbB2 and c-erbB3 in endometrioid carcinoma of the ovary. Chin Med Sci J 12:67–70PubMed
Zurück zum Zitat MacFarlane R, Speers C, Masoudi H et al (2008) Molecular changes in the primary breast cancer versus the relapsed/metastatic lesion from a large population-based database and tissue microarray series. J Clin Oncol 26:abstr 1000 MacFarlane R, Speers C, Masoudi H et al (2008) Molecular changes in the primary breast cancer versus the relapsed/metastatic lesion from a large population-based database and tissue microarray series. J Clin Oncol 26:abstr 1000
Zurück zum Zitat Motojima K, Furui J, Kohara N et al (1994) erbB-2 Expression in well-differentiated adenocarcinoma of the stomach predicts shorter survival after curative resection. Surgery 115:349–354PubMed Motojima K, Furui J, Kohara N et al (1994) erbB-2 Expression in well-differentiated adenocarcinoma of the stomach predicts shorter survival after curative resection. Surgery 115:349–354PubMed
Zurück zum Zitat Oshima CT, Lanzoni VP, Iriya K et al (2001) C-erbB-2 oncoprotein in gastric carcinoma: correlation with clinical stage and prognosis. Int J Biol Markers 16:250–254PubMed Oshima CT, Lanzoni VP, Iriya K et al (2001) C-erbB-2 oncoprotein in gastric carcinoma: correlation with clinical stage and prognosis. Int J Biol Markers 16:250–254PubMed
Zurück zum Zitat Pinto-de-Sousa J, David L, Almeida R et al (2002) c-erb B-2 expression is associated with tumor location and venous invasion and influences survival of patients with gastric carcinoma. Int J Surg Pathol 10:247–256. doi:10.1177/106689690201000402 CrossRefPubMed Pinto-de-Sousa J, David L, Almeida R et al (2002) c-erb B-2 expression is associated with tumor location and venous invasion and influences survival of patients with gastric carcinoma. Int J Surg Pathol 10:247–256. doi:10.​1177/​1066896902010004​02 CrossRefPubMed
Zurück zum Zitat Potrc S, Gadiijev E, Hajdinjak T et al (2007) Clinicopathological and immunohistochemical markers after radical gastrectomy for gastric cancer. Hepatogastroenterology 54:308–314PubMed Potrc S, Gadiijev E, Hajdinjak T et al (2007) Clinicopathological and immunohistochemical markers after radical gastrectomy for gastric cancer. Hepatogastroenterology 54:308–314PubMed
Zurück zum Zitat Saucier C, Papavasiliou V, Palazzo A et al (2002) Use of signal specific receptor tyrosine kinase oncoproteins reveals that pathways downstream from Grb2 or Shc are sufficient for cell transformation and metastasis. Oncogene 21:1800–1811. doi:10.1038/sj.onc.1205261 CrossRefPubMed Saucier C, Papavasiliou V, Palazzo A et al (2002) Use of signal specific receptor tyrosine kinase oncoproteins reveals that pathways downstream from Grb2 or Shc are sufficient for cell transformation and metastasis. Oncogene 21:1800–1811. doi:10.​1038/​sj.​onc.​1205261 CrossRefPubMed
Zurück zum Zitat Suzuki T, Tsuda T, Haruma K et al (1995) Growth of human gastric carcinomas and expression of epidermal growth factor, transforming growth factor-alpha, epidermal growth factor receptor and p185c-erbB-2. Oncology 52:385–391CrossRefPubMed Suzuki T, Tsuda T, Haruma K et al (1995) Growth of human gastric carcinomas and expression of epidermal growth factor, transforming growth factor-alpha, epidermal growth factor receptor and p185c-erbB-2. Oncology 52:385–391CrossRefPubMed
Zurück zum Zitat Varis A, Wolf M, Monni O et al (2002) Targets of gene amplification and overexpression at 17q in gastric cancer. Cancer Res 62:2625–2629PubMed Varis A, Wolf M, Monni O et al (2002) Targets of gene amplification and overexpression at 17q in gastric cancer. Cancer Res 62:2625–2629PubMed
Zurück zum Zitat Vizoso FJ, Corte MD, Alvarez A et al (2004) Membranous levels of c-erbB-2 oncoprotein in gastric cancer: their relationship with clinicopathological parameters and their prognostic significance. Int J Biol Markers 19:268–274PubMed Vizoso FJ, Corte MD, Alvarez A et al (2004) Membranous levels of c-erbB-2 oncoprotein in gastric cancer: their relationship with clinicopathological parameters and their prognostic significance. Int J Biol Markers 19:268–274PubMed
Zurück zum Zitat Yano T, Doi T, Ohtsu A et al (2006) Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol Rep 15:65–71PubMed Yano T, Doi T, Ohtsu A et al (2006) Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol Rep 15:65–71PubMed
Zurück zum Zitat Yokoyama H, Ikehara Y, Kodera Y et al (2006) Molecular basis for sensitivity and acquired resistance to gefitinib in HER2-overexpressing human gastric cancer cell lines derived from liver metastasis. Br J Cancer 95:1504–1513. doi:10.1038/sj.bjc.6603459 CrossRefPubMed Yokoyama H, Ikehara Y, Kodera Y et al (2006) Molecular basis for sensitivity and acquired resistance to gefitinib in HER2-overexpressing human gastric cancer cell lines derived from liver metastasis. Br J Cancer 95:1504–1513. doi:10.​1038/​sj.​bjc.​6603459 CrossRefPubMed
Zurück zum Zitat Yu GZ, Chen Y, Long YQ et al (2008) New insight into the key proteins and pathways involved in the metastasis of colorectal carcinoma. Oncol Rep 19:1191–1204PubMed Yu GZ, Chen Y, Long YQ et al (2008) New insight into the key proteins and pathways involved in the metastasis of colorectal carcinoma. Oncol Rep 19:1191–1204PubMed
Metadaten
Titel
Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance
verfasst von
Guan Zhen Yu
Ying Chen
Jie Jun Wang
Publikationsdatum
01.10.2009
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 10/2009
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-009-0574-8

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