HER2 (c-erbB-2) oncoprotein expression in colorectal adenocarcinoma: an immunohistological study using three different antibodies.

Arnaout, Abed; Dawson, Peter; Soomro, S; Taylor, P; Theodorou, N. A.; Feldmann, Marc; Fendly, Brian M.; Shepard, H M; Shousha, Sami

doi:10.1136/jcp.45.8.726

Cited by 24 publications

(18 citation statements)

References 7 publications

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“…Studies that scored intracytoplasmic staining as positive reported larger frequencies, whereas studies that reported only membrane staining as positive was scored lower or zero frequency. [16][17][18][19][22][23][24] The results of the current study appear similar to those of Osako et al, 22 who used the same antibody as in our study. They observed membranous staining in only 3% of colorectal carcinomas (three of 100), and demonstrated gene amplification by Southern blot analysis in one of the three.…”

Section: Discussionsupporting

confidence: 81%

“…Previous IHC studies examining HER-2 expression reported different percentages of positive cells, ranging from 0 to 100%. [16][17][18][19][20][21][22][23][24] The major cause of these discrepancies seems to be the different criteria for evaluating the results. Studies that scored intracytoplasmic staining as positive reported larger frequencies, whereas studies that reported only membrane staining as positive was scored lower or zero frequency.…”

Section: Discussionmentioning

confidence: 99%

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Protein overexpression and gene amplification of HER-2 and EGFR in colorectal cancers: an immunohistochemical and fluorescent in situ hybridization study

et al. 2004

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Overexpression of HER-2 and the epidermal growth factor receptor (EGFR) has been observed in many cancers, sometimes accompanied by gene amplification. To assess whether novel chemotherapies targeting these overexpressed proteins may be effective for the treatment of colorectal cancers, we examined the exact frequency of HER-2 and EGFR overexpression, the relationship between gene amplification and protein expression, and the heterogeneity of gene amplification within and between primary and metastatic tumors. We evaluated 244 colorectal cancers immunohistochemically. All tumors found to overexpress HER-2 or EGFR were further analyzed for gene amplification by fluorescent in situ DNA hybridization. Overexpression of HER-2 and EGFR was found in 8 (3%) and 19 (8%) of the 244 colorectal carcinomas, respectively. Gene amplification was observed in 100 and 58% of the tumors exhibiting HER-2 and EGFR overexpression, respectively. HER-2 amplification in cancer cells was characterized by clusters of hybridization signals, suggesting amplicons in homogeneously staining regions that were predominant in most primary and metastatic tumors. EGFR amplification, observed as scattered signals reminiscent of amplicons in double minute chromosomes, or coamplification of EGFR with the centromeric regions was observed as a minor population within primary tumors, and found in variety of populations in metastatic tumors. Overexpression of HER-2 and EGFR were observed in only a small fraction of colorectal carcinomas, but were frequently accompanied by gene amplification. The HER-2 gene is located on chromosomal region 17q11.2-q12 and the EGFR gene is located on 7p12. These encode 185 kDa (p185) and 170 kDa plasma membrane glycoproteins, respectively. They share approximately 50% overall homology and are composed of an N-terminus extracellular ligand-binding domain, a transmembrane lipophilic segment, and a C-terminus intracellular region containing a tyrosine kinase domain.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Protein overexpression and gene amplification of HER-2 and EGFR in colorectal cancers: an immunohistochemical and fluorescent in situ hybridization study

et al. 2004

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“…c-erbB-2 gene amplification and overexpression of its protein are correlated with a poor prognosis in patients with breast [5][6][7][8][9] and gastric adenocarcinomas [10][11][12]. In colorectal cancer, the c-erbB-2 gene amplified and overexpressed on plasma membrane was reported to have a relatively low incidence, as determined by Southern blot hybridization [13][14][15][16] and in immunohistochemical studies [17][18][19][20]. The biological and clinical significance of c-erbB-2 overexpression in cases of colorectal carcinoma is less evident.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Study of c-erbB-2 Protein in Colorectal Cancer and the Correlation with Patient Survival

Osako¹,

Miyahara²,

Uchino³

et al. 1998

Oncology

104

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We related events in immunohistochemical studies on formalin-fixed, paraffin-embedded preparations of 146 colorectal cancer patients. One hundred (68.5%) revealed cytoplasmic staining and only 3 of the 100 showed membranous staining. Western blot analysis revealed proteins with molecular masses of 185 and 155 kD following immunohistochemical membranous and cytoplasmic staining, but only a 155-kD protein following cytoplasmic staining. Amplification of the c-erbB-2 gene was detected in 2 of 44 cases (4.5%). Cytoplasmic c-erbB-2 overexpression correlated with tumor size (p < 0.01), subserosal invasion (p < 0.05), liver metastasis (p < 0.01) and Dukes’ classification. Overall survival rates and survival rates for Dukes’B patients were significantly lower in the group with cytoplasmic c-erbB-2 overexpression than in the group without cytoplasmic c-erbB-2 overexpression. Multivariate regression analysis showed cytoplasmic c-erbB-2 overexpression to be an independent prognostic factor for colorectal cancer. These results suggest that overexpression of cytoplasmic c-erbB-2 protein plays an important role in the progression of colorectal cancer and is considered to be an independent prognostic indicator of this lesion.

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“…HER2 expression has been exploited as a therapeutic drug target in the form of trastuzumab [3, 4], a humanized monoclonal antibody targeted to the extracellular domain of HER2 [review, see 5]. In addition to breast cancer, HER2 is also associated with other malignancies including ovarian cancer [6], gastric cancer [7] (including premalignant lesions [8]), colon cancer [9], pancreatic cancer [10], and bladder cancer [11]. The identification of HER2 expression in other malignancies has led to HER2-directed therapeutic strategies for additional neoplastic diseases.…”

Section: Introductionmentioning

confidence: 99%

HER2/ERBB2 immunoreactivity in human retinoblastoma

Seigel¹,

Sharma

Hackam

et al. 2015

Tumor Biol.

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Retinoblastoma (RB) is an ocular malignancy of early childhood. Although mutations in the Rb1 gene and expression of stem cell markers have been identified in RB, additional information on RB-specific alterations in signaling pathways and protein expression would be useful for the design of targeted RB therapies. Here we have evaluated the expression of HER2 (ERBB2) in RB. HER2 is a member of the epidermal growth factor family, which is overexpressed in breast, ovarian, gastric, colorectal, pancreatic, and endometrial cancers in a stratified manner. Overexpression and gene amplification of HER2 is associated with aggressive malignancies, accompanied by chemoresistance and poor outcomes. In this study, we present the first evidence of HER2 immunoreactivity in retinoblastoma, as shown by immunocytochemistry, flow cytometry, and western immunoblot, with validation by reverse transcription PCR (RT-PCR) in both RB cell lines and clinical RB tumors. Our results suggest that the HER2 protein expressed in RB is a truncated version that spares the trastuzumab binding site, while HER2 is not detected in normal ocular tissues. Our discovery of HER2 expression in RB may lead to innovative and targeted drug treatment options designed to spare the eye and preserve vision in RB patients.

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HER2 (c-erbB-2) oncoprotein expression in colorectal adenocarcinoma: an immunohistological study using three different antibodies.

Cited by 24 publications

References 7 publications

Protein overexpression and gene amplification of HER-2 and EGFR in colorectal cancers: an immunohistochemical and fluorescent in situ hybridization study

Protein overexpression and gene amplification of HER-2 and EGFR in colorectal cancers: an immunohistochemical and fluorescent in situ hybridization study

Immunohistochemical Study of c-erbB-2 Protein in Colorectal Cancer and the Correlation with Patient Survival

HER2/ERBB2 immunoreactivity in human retinoblastoma

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