Haymaker Gene Expression in Malignant and Normal Gynecologic Tissues

Mark E. Borowsky ¹, Ballabh Das ¹, Constantine A. Axiotis ¹, Edmond S. Malka ¹, Ovadia Abulafia ¹ and Allen J. Norin ^1*

¹ Department of Obstetrics and Gynecology (MEB,OA), Department of Surgery (BD,AJN), Transplant Immunology and Immunogenetics Laboratory (BD,AJN), Department of Medicine (BD,AJN), Department of Anatomy and Cell Biology (AJN), Department of Pathology (CAA), and Department of Preventive Medicine and Community Health (ESM), State University of New York Downstate Medical Center, Brooklyn, New York

Submitted on June 21, 2005
Accepted on 3 February 2006

	Abstract

We previously reported that cell lines established from human carcinomas and leukemias / lymphomas expressed high levels of an intracellular membrane bound protein, Haymaker, whereas, cell lines derived from non malignant connective tissue cells and lymphoid cells expressed low levels of this gene product. To determine if these findings reflect neoplastic transformation or alternatively, tissue specificity, we examined the expression of Haymaker in gynecologic organs with and without tumor by immunohistochemical and molecular methods. A highly specific, affinity purified rabbit polyclonal antibody against a 25-mer Haymaker - peptide was used for immunohistochemical staining and morphometric analysis of 85 tissue specimens. Immunohistochemical studies demonstrate, for the first time, that Haymaker protein is highly expressed in epithelial cells of the endometrium of the normal uterus and to a somewhat lesser extent in the mucosa of the normal vagina and cervix but is poorly expressed or absent in cells of the connective tissue and smooth muscle strata of these organs (p-value <0.005). Significant differences in Haymaker expression, as assessed by immunohistochemistry, between malignant and normal gynecologic tissues were not observed (p=0.27). In RT-PCR studies Haymaker mRNA transcripts were more readily detected in the endometrium of uteri bearing epithelial tumors then in the endometrium of normal uteri. The latter finding is consistent with the presence of a greater proportion of epithelial derived cells relative to connective tissue cells in cancer specimens compared with normal specimens. In summary, the expression of Haymaker protein does not appear to be a marker of malignant transformation of the epithelium of gynecologic organs but rather distinguishes both normal and malignant epithelial cells from normal connective tissue and smooth muscle cells.
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