Expression of erbB-3 protein in colorectal adenocarcinoma: correlation with poor survival

Kapitanović, Sanja; Radošević, Senka; Slade, Neda; Kapitanovic, M; Anđelinović, Šimun; Ferenčić, Željko; Tavassoli, Mahvash; Spaventi, Šime; Pavelić, Krešimir; Spaventi, Radan

doi:10.1007/s004320050034

Cited by 44 publications

(26 citation statements)

References 28 publications

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“…Furthermore, c-erbB-3 itself, to some extent, affects disease-free survival. Similar results were obtained for breast carcinoma, i.e., c-erbB-3 is related to tumour size and tumour type prognostic group (Travis et al, 1996), and for colorectal carcinoma, i.e., cases without c-erbB-3 expression show a favourable outcome for DFS of the patients (Kapitanovic et al, 2000). On the other hand, such relationships have not been found with other neoplasms such as carcinoma of the esophagus (Freiss et al, 1999), stomach (Sanidas et al, 1993) and ovary (Simpson et al, 1995).…”

Section: Discussionsupporting

confidence: 79%

“…Thus far, of the four receptors, the expression of EGF-R and c-erbB-2 has been investigated in various neoplasms, including malignancies of the liver and biliary tract (Brunt and Swanson, 1992;Collier et al, 1992;Nakapoulou et al, 1994;Lee and Pirdas, 1995;Kira et al, 1997;Terada et al, 1998). The other two receptors, c-erbB-3 and c-erbB-4, have only been studied in depth for a few neoplasms (Sanidas et al, 1993;Simpson et al, 1995;Shintani et al, 1995;Haugen et al, 1996;Travis et al, 1996;Bobrow et al, 1997;Bodey et al, 1997;Chow et al, 1997;Ibrahim et al, 1997;Srinivasan et al, 1998Srinivasan et al, , 2000Suo et al, 1998;Freiss et al, 1999;Haussler et al, 1999;Kapitanovic et al, 2000;Kew et al, 2000), and little is known about their expression in hepatic malignancies. In this study, we investigated the expression of all four components of this family in a large series of HCC to evaluate their clinical significance and to identify the factors reflecting the development of this carcinoma.…”

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confidence: 99%

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Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma

Ito

Takeda

Sakon³

et al. 2001

Br J Cancer

269

204

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In order to elucidate the clinical significance of the erbB family, epidermal growth factor receptor (EGF-R), c-erbB-2, c-erbB-3 and c-erbB-4 in hepatocellular carcinoma (HCC), we investigated the expression of these proteins by means of immunohistochemistry for HCC as well as adjacent noncancerous lesions. EGF-R was expressed in 68% of the HCC examined and showed correlation with the proliferating activity, stage, intrahepatic metastasis and carcinoma differentiation. c-erbB-2 was expressed in only 21% of the cases and showed no relationships with the clinicopathological parameters. c-erbB-3 protein was observed in 84% of the HCC and 38.1% of the noncancerous lesions. Its expression in HCC was equal to or greater than noncancerous lesions in 90.5% of the cases, and was related to the stage, portal invasion, cell proliferating activity, tumour size, intrahepatic metastasis and carcinoma differentiation. c-erbB-4 protein was expressed in 61.0% of HCC and in as much as 86.1% of the noncancerous lesions. Unlike the expression of c-erbB-3, that of c-erbB-4 in HCC was less than that of the adjacent noncancerous lesions in 51.2% of the cases. No statistical significance could be established between this protein expression in HCC and clinicopathological features. EGF-R and c-erbB-3 affected disease-free survival, but were not recognized as independent prognostic factors by multivariate analysis. The present study suggests that, of the four receptors, EGF-R and c-erbB-3 play important roles in the progression of HCC. © 2001 Cancer Research Campaign www.bjcancer.com

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Section: Discussionsupporting

confidence: 79%

mentioning

confidence: 99%

Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma

Ito

Takeda

Sakon³

et al. 2001

Br J Cancer

269

204

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“…HER3 has previously been reported to be expressed in 36-89% of CRC (5,23,25,(46)(47)(48). In our study, the fraction strongly HER3 expressing cases were only 16 and 18% for primary tumors and lymph node metastases, respectively.…”

Section: ------------------------------------------------------------contrasting

confidence: 43%

EGFR, HER2 and HER3 expression in primary colorectal carcinomas and corresponding metastases: Implications for targeted radionuclide therapy

Wei

Shui²,

Zheng³

et al. 2010

Oncol Rep

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Abstract. Members of the epidermal growth factor receptor, EGFR, family are interesting as targets for radionuclide therapy using targeting agents labeled with ·-or ß-emitting radionuclides, especially when EGFR-positive colorectal carcinomas, CRC, are resistant to EGFR inhibiting agents like cetuximab and various tyrosine kinase inhibitors. The expression of EGFR, HER2 and HER3 was therefore analyzed in CRC samples from primary tumors, corresponding lymph node metastases and, in a few cases, liver metastases. The expression of HER2 and EGFR was scored from immunohistochemical preparations using the HercepTest criteria 0, 1+, 2+ or 3+ for cellular membrane staining while HER3 expression was scored as no, weak or strong cytoplasm staining. Material from 60 patients was analyzed. The number of EGFR 2+ or 3+ positive primary tumors was 16 out of 56 (29%) and for lymph node metastases 8 out of 56 (14%) whereas only one out of nine (11%) liver metastases were positive. Thus, there was lower EGFR positivity in the metastases. Only one among 53 patients was strongly HER2 positive and this in both the primary tumor and the metastasis. Eight out of 49 primary tumors (16%) were strongly HER3 positive and the corresponding numbers for lymph node metastases were 9 out of 49 (18%) and for liver metastases 2 out of 9 (22%). The observed number of strongly EGFR positive cases was somewhat low but EGFR might be, for the cases with high EGFR expression in metastases, a target for radionuclide therapy. HER2 seems not to be of such interest due to rare expression, neither HER3 due to mainly expression in the cytoplasm. The requirements for successful EGFR targeted radionuclide therapy are discussed, as well as patient inclusion criteria related to radionuclide therapy.

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“…GEO cells express autocrine transforming growth factor ␣ and have been shown to be responsive to different ErbB1-targeted therapies (48 -50). However, we found that GEO cells were also very sensitive to the ErbB2/ErbB3 ligand heregulin, a pathway present in colon cancer (51)(52)(53)(54). One would not expect that targeting ErbB1 would inhibit heregulin-stimulated growth in these cells (heregulin treatment did not result in any detectable activation of ErbB1).…”

Section: Discussionmentioning

confidence: 77%

Blockade of Epidermal Growth Factor- or Heregulin-Dependent ErbB2 Activation with the Anti-ErbB2 Monoclonal Antibody 2C4 Has Divergent Downstream Signaling and Growth Effects

Jackson

Clair

Sliwkowski³

et al. 2004

Cancer Research

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Due to heterodimerization and a variety of stimulating ligands, the ErbB receptor system is both diverse and flexible, which proves particularly advantageous to the aberrant signaling of cancer cells. However, specific mechanisms of how a particular receptor contributes to generating the flexibility that leads to aberrant growth regulation have not been well described. We compared the utilization of ErbB2 in response to epidermal growth factor (EGF) and heregulin stimulation in colon carcinoma cells. Anti-ErbB2 monoclonal antibody 2C4 blocked heregulinstimulated phosphorylation of ErbB2 and ErbB3; activation of mitogenactivated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and Akt; proliferation; and anchorage-independent growth. 2C4 blocked EGF-mediated phosphorylation of ErbB2 and inhibited PI3K/Akt and anchorage-independent growth but did not affect ErbB1 or MAPK. Immunoprecipitations showed that ErbB3 and Grb2-associated binder (Gab) 1 were phosphorylated and associated with PI3K activity after heregulin treatment and that Gab1 and Gab2, but not ErbB3, were phosphorylated and associated with PI3K activity after EGF treatment. These data show that monoclonal antibody 2C4 inhibited all aspects of heregulin signaling as well as anchorage-independent and monolayer growth. Furthermore, we identify ErbB2 as a critical component of EGF signaling to the Gab1/ Gab2-PI3K-Akt pathway and anchorage-independent growth, but EGF stimulation of MAPK and monolayer growth can occur efficiently without the contribution of ErbB2.

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Expression of erbB-3 protein in colorectal adenocarcinoma: correlation with poor survival

Abstract: These findings demonstrate that erbB-3 protein expression could serve as a prognostic factor in colorectal malignancies.

Cited by 44 publications

References 28 publications

Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma

Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma

EGFR, HER2 and HER3 expression in primary colorectal carcinomas and corresponding metastases: Implications for targeted radionuclide therapy

Blockade of Epidermal Growth Factor- or Heregulin-Dependent ErbB2 Activation with the Anti-ErbB2 Monoclonal Antibody 2C4 Has Divergent Downstream Signaling and Growth Effects

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