Three projects, correlation of immunophenotype and morphology with clinical outcome in lobular carcinoma of the breast, Barrett-associated adenocarcinomas of the esophagus, and high-grade carcinomas of the uterine corpus, incorporate my interest in immunohistochemistry and histopathology of solid tumors. In each tumor system, we will attempt to evaluate antibodies against proliferation-associated antigens, tumor suppressor gene products, cell-cycle regulation proteins, and adhesion molecules.

The morphologic subtypes and immunophenotype of lobular carcinomas of the breast have not been well described; most breast research has focused on the more common ductal carcinoma subtype. We hope to define morphologic subgroups of lobular carcinomas that are prognostically and therapeutically useful to clinicians. We would then like to correlate these morphologic and clinical findings with potential differences in proliferation, tumor suppressor gene abnormalities, and cell-cycle regulation. We are also interested in evaluating for differences in adhesion molecule expression in lobular carcinoma in situ versus infiltrating lobular carcinoma and infiltrating ductal carcinoma.

Progressive abnormalities in proliferation and tumor suppressor gene expression have been well documented in esophageal intestinal metaplasia, dysplasia, and adenocarcinoma. In addition, we are interested in the expression of angiogenesis agents and cell-cycle regulatory proteins in Barrett-associated dysplasia and adenocarcinoma. We also plan to study the role of apoptosis in Barrett-adenocarcinoma tumor progression and response to therapy.

Uterine papillary serous carcinoma is a morphologically and clinically distinct type of high-grade endometrial carcinoma. The reasons for this tumor's particular aggressiveness are not known. We plan to investigate the relationship between aggressive clinical behavior, morphology, and expression of tumor suppressor genes, cell-cycle regulatory proteins, and adhesion molecules in poorly differentiated carcinomas of the endometrium. We also plan to study the clinicopathologic features of poorly differentiated endometrial carcinomas that are either apparently non-invasive or minimally invasive.