Expression of Her-2 in Carcinomas of the Esophagus

Abstract

The human epidermal growth factor receptor-2 gene (HER-2) encodes for a membrane-bound tyrosine kinase (Her-2), which is overexpressed in various human cancers. Her-2-targeted therapy has recently been shown to be beneficial for patients with advanced gastric cancer. Her-2 protein expression was investigated in 341 esophageal carcinomas [152 squamous cell carcinomas (SCC), 189 adenocarcinomas (AC)], 39 cases of Barrett mucosa, and 11 cases of squamous cell dysplasia. HER-2 gene amplification was assessed by colorimetric in-situ hybridization. Positive Her-2 status was found in 15.3% of ACs and 3.9% of SCCs. Positive Her-2-status was more common in dysplastic Barrett mucosas compared with nondysplastic ones (P=0.04). In 26% of the patients with ACs who had received neoadjuvant chemotherapy (n=39), the Her-2 status of pretherapeutic biopsies was different compared with subsequent surgical specimens. There was no statistically significant correlation between Her-2 status and patients' survival. Although Her-2 overexpression is rare in SCCs, it is found in 15.3% of ACs, where amplification of HER-2 gene and overexpression of Her-2 protein seem to be early events in carcinogenesis. The evaluation of Her-2 status in tumor biopsies and in particular in the context with possible alterations after neoadjuvant treatment can potentially lead to false Her-2-staging. Although Her-2-overexpression in esophageal cancer seems to have no influence on patients' survival, these subtypes of esophageal ACs have to be considered as targets for an anti-Her-2 therapy.

HER2 Gene Amplification and Protein Expression in Pancreatic Ductal Adenocarcinomas

“…4,16,17,32 Nevertheless, due to the detection of novel mechanisms and development of targeted therapies, small and smaller subgroups of cancer patients are identified, which may benefit from a targeted therapy. Therefore, for example, in non-small cell lung cancer, the rates of patients with tumors showing ALK translocations or EGFR mutations, which represent targets for novel therapies, are also below 10%.…”

“…[5][6][7][8] The role of HER has also been studied in several other cancers, including bladder cancer, endometrial cancer, gastroesophageal cancer, ovarian cancer, lung cancer, osteosarcoma, and prostate cancer. [9][10][11][12][13][14][15][16][17] Recently, the monoclonal HER2-blocking antibody trastuzumab has also been FDA approved for the treatment of HER2 overexpressing advanced stage gastroesophageal cancer, in addition to breast cancer. 18 Despite combination of surgical treatment with adjuvant chemotherapy, the outcome of pancreatic ductal adenocarcinoma (PDAC) is one of the worst of all malignancies as it is the fourth leading cause of death from cancer in the United States.…”

Treatment Approaches to Esophagogastric Junction Tumors

“…Siewert type III tumors involve intestinal metaplasia less often, and there is a higher proportion of the undifferentiated type. Siewert type II tumors fall between types I and III in most characteristics, but the proportion of human epidermal growth factor receptor 2 positivity in type II tumors is higher than in types I and III [8]. Although there is almost an even distribution among these three types in Western countries, there are very few Siewert type I patients in Eastern countries [7,9,10].…”

Expression levels of HER2 and MRP1 are not prognostic factors of long-term survival in 829 patients with esophageal squamous cell carcinoma

“…In addition, HER2 is a therapeutic target in several types of cancer. Previous studies have observed that the oncogene HER2/neu was overexpressed in 2.0-19.1% cases of ESCC (6)(7)(8)(9)(10)(11)(12)(13), and increased protein expression levels of HER2 have been previously observed in EC (14,15) and ESCC (6,7). However, the role of HER2 in ESCC remains controversial (6,7,9,10,12,(16)(17)(18)(19).…”