Expression of c-erbb-2 in upper gastrointestinal tract carcinoma and its associations with metastasis

• Main Author: Yunus, Nor Hayati
• Format: Thesis
• Language: English
• Published: 2012
• Subjects: R Medicine (General); RC254-282 Neoplasms. Tumors. Oncology (including Cancer); RC799-869 Diseases of the digestive system. Gastroenterology
• Online Access: http://eprints.usm.my/60780/1/DR%20NOR%20HAYATI%20BINTI%20YUNUS%20-%20e.pdf; http://eprints.usm.my/60780/

The availability of drugs therapy targeting the EGFR signaling pathways forms a basis foundation for accurate diagnosis of cancer that will predict responses to treatment. Data of HER2 protein expression and gene amplification in upper gastro intestinal cancer is still conflicting but its expression is firmly established in adenocarcinoma of upper gastrointestinal tract. The expression or its gene amplification is related with poor prognosis of the disease. Experience from HER2 testing in breast cancer provides the importance of quality of HER2 interpretation that guides its application in the upper gastro intestinal cancer. Indeed, standardization of HER2 interpretation in upper gastro intestinal cancer is even important. ToGA trials have showed that immunohistochemistry should be the initial testing method and followed by FISH or CISH to retest. In this study, we determine and comparing the expression of HER2 in esophageal and gastric carcinoma and correlate its expression with the presence of lymph node metastasis and survival status. A cross-sectional study was conducted on 66 cases of upper gastrointestinal carcinoma in which 30 cases were of gastric carcinoma and 36 cases were of esophageal carcinoma. All of these cases were tissue biopsies from archived paraffin embedded tissue blocks from Hospital Universiti Sains Malaysia between Januaryl998 until August 2011. All specimens were stained with Hematoxylin and Eosin followed by immunohistochemical stain for HER2. Positive staining was demonstrated by the presence immunohistochemical stain for HER2. Positive staining was demonstrated by the presence basolateral or lateral membranous reactivity where as negative stain was tumor with faint or no membranous reactivity at all. We observed that 7 (10.6%) out of 66 cases of upper gastrointestinal carcinoma were positive for HER2. The frequency of HER2 positivity is more in esophageal carcinoma than gastric carcinoma. Four (6.1%) of the positive cases were esophageal adenocarcinoma and one positivity (1.5%) in esophageal squamous cell carcinoma. The other 2(3%) were contributed by intestinal type gastric carcinoma. Most of the cases with positive HER2 were moderately differentiated tumor (9.1%). Only one case (1.5%) of poorly differentiated tumor was found to express HER2. Only 3 positive HER2 cases (8.8%) have evidence of lymph nodes metastasis. Of the 7 positive cases, 6 of them were still alive with disease within 1 year after diagnosis. However, all the result showed no statistical significant associations with HER2 expression. Identification of HER2 protein expression in upper gastro intestinal cancer is rather important as in breast cancer to justify patients who might benefit from anti-HER2 therapy. This will aid in proper patients selection for optimum therapy of this cancers. Our findings suggest that there are variable expressions of HER2 interpretation in both esophageal and gastric carcinoma even though statistically our results were not significant. This emphasized that immunohistochemistry method is not a stand-alone test in order to evaluate HER2 protein expression in this heterogenous tumor.