The HER-2/neuOncogene in Tumors of the Gastrointestinal Tract

Abstract

The HER-2/neu oncogene is localized to chromosome 17q and shares significant homology with the epidermal growth factor receptor. As a result of its potential role in the selection of therapy, HER-2/neu testing has reached near-standard-of-practice status in breast cancer. There is considerable interest in HER-2/neu as a prognostic factor and target of therapy in tumors of the gastrointestinal tract. In this review of HER-2/neu expression in esophageal squamous cell carcinoma and adenocarcinomas of the esophagus, stomach, and colon, a wide range of expression of HER-2/neu from 0 to 83% likely reflects both differences in methods and reagents, as well as study bias associated with patient selection (i.e., early versus advanced disease). For esophageal squamous cell carcinoma, little information exists as to the prognostic significance of HER-2/neu expression. In adenocarcinoma associated with Barrett's esophagus there is contradictory data. However, most of the information available indicates that this marker has significant prognostic value. In gastric adenocarcinoma, the wide expression range may truly reflect patient selection because HER-2/neu positivity appears linked to advanced rather than early disease with limited invasion. The majority of studies favor a significant prognostic value of HER-2/neu status for this tumor. Finally, in colorectal cancer HER-2/neu overexpression also appears to be a significant adverse outcome indicator as judged by the current published literature. In conclusion, given that either HER-2/neu protein overexpression or gene amplification is associated with approximately one-fourth of all gastrointestinal tract malignancies, strategies designed to employ the marker in therapy selection appear warranted. During the next several years it will not be surprising to see these tumors treated with antiHER-2/neu modalities such as Herceptin, likely in combination with other agents initially for patients with advanced disease, and possibly for individuals with high-risk lesions in an adjuvant setting.

Close association between HER-2 amplification and overexpression in human tumors of non-breast origin

“…For all of these tumor entities, HER-2 positivity (overexpression and/or amplification) had been previously described. [29][30][31][32] For example, HER-2 positivity for gastric cancer has been Of most tumor categories, we analyzed around 50 cases or even fewer. This rather low number raises the possibility that rare HER-2 amplification/overexpression may have been missed in some tumor entities.…”

Assessment of a HER2 scoring system for colorectal cancer: results from a validation study

“…3,22,28 ERBB2 staining in gastric cancer is not directly correlated to ERBB2 amplification, with up to 30% of ERBB2 amplification-positive cases showing only focal staining or diffuse staining in o 30% of tumor cells. 24 On the contrary, ERBB2 protein expression and gene amplification in our colorectal cancer samples tallied quite accurately. None of the ERBB2 expression-negative colorectal cancer was amplified, whereas all immunohistochemistry-positive colorectal cancers were, leaving only the equivocal staining tumors in a grey zone.…”

“…It focused on ERBB2 amplification, as preclinical data supporting the HERACLES trial suggested amplification and not only overexpression as the predictive marker for response to anti-ERBB2 treatment. 10 Within this algorithm, to minimize false positives owing to unspecific staining, we disregarded cytoplasmic ERBB2 expression, 19,24 as in breast cancer only membrane-bound ERBB2 expression is associated with ERBB2 gene amplification. 19 As in breast cancer, in our colorectal cancer series, ERBB2 overexpression associated with gene amplification was also already clearly membrane bound at low magnification.…”

Relationship of expression of HER 2 protein according to histological type tumors by lauren in gastric cancer

“…26 Gastric cancers of intestinal type have also shown higher rates of expression of HER2 protein than gastric cancer of diffused type (p<0,05) in one Korean study. 27 In the published studies it is determined that proximal gastric cancers with intestinal phenotype have higher existence of HER2 expression than distal diffused gastric cancers ( Before it came to the knowledge of existence of prognostic factors on molecular level, clinicalpathological parameters were the only one known predictive and prognostic factors until then. To the recent proven prognostic variables belong the tumor stage, histological gradus, tumor size, localization, existence of lymphovascular invasion, age and gender of the patient, and molecular tumor markers p53, E-cadherin, CD-34, cErbB2, CA 72-4, CEA which recently gained popularity as potential prognostic indicators for predicting the tumor behavior.…”