Immunohistochemical and Molecular Pathologic Features of Esophagus Carcinomas

Esophageal carcinoma is a very heterogeneous group including squamous, adenoid, adenoid cystic neuroendocrine, and other rare carcinomas. Origins and precancerous lesions of each subtype are completely different from each other. As a result, the immunohistochemical and molecular pathologic changes of these subgroups are totally different from each other. Barret’s dysplasia is a precancerous lesion for adenocarcinoma of the esophagogastric junction. Immunohistochemistry of p53, AMACR, Ki-67 proliferation index, and IMP3 is sometimes useful for differentiating between non-dysplastic and dysplastic epithelium. The most common benefit of immunohistochemistry is in differential diagnosis of poorly differentiated esophagus primary esophageal carcinomas. In differential diagnosis, CK5/6, p40, and CK7 can be used. Squamous cell carcinomas are strongly positive for CK5/6 and p40, but adenocarcinomas are strongly positive for CK7 and negative for squamous markers. Esophageal adenoid cystic carcinoma is of myoepithelial origin and positive for myoepithel markers such as p63, S100, SMA, and calponin. In the diagnosis of neuroendocrine carcinoma, neuroendocrine differentiation should be confirmed immunohistochemically by the expression of chromogranin A and synaptophysin. Prognosis of the neuroendocrine carcinoma is directly relevant with grading which depends on the Ki-67 proliferation index. The other use of immunohistochemistry may be with the metastatic or invading carcinomas and primary esophageal carcinomas. Genetic alterations are also very important in the carcinogenetic pathway of both adenocarcinoma and squamous carcinoma. But it has only limited value in choosing the targeted therapy for adenocarcinoma of the esophagus. Molecular changes in adenocarcinoma of the esophagus are directly related to outcome and treatment protocol. Trastuzumab, an antibody targeting the human EGFR family member ERBB2 (HER2), is accepted to be used in the targeted therapy of advanced or metastatic adenocarcinoma of the esophagogastric junction in combination with other chemotherapy. Indication of this therapy is the detection of ERBB2 gene by immunohistochemical and molecular pathologic techniques.