Dr. Khushbakhat Mittal, MD

1. Site specific cell death in ovarian serous carcinoma: We have identified a location specific cell death in invasive ovarian serous carcinomas, micro-invasive serous borderline tumors, and in serous borderline tumors with invasive implants. The cell death occurs next to areas of stroma, resulting in clusters of cells lying in spaces or clefts. We plan to study the mechanism of this tumor cell death. Understanding of these mechanisms may lead to identification of possible novel mechanisms of cell death and new therapeutic targets in ovarian serous carcinomas and serous borderline tumors. 2. Pathogenesis of Uterine Leiomyomata: Studies are currently underway in our lab. to investigate the role of TSC2, insulin signaling pathway, steroid receptors and steroid receptor co-factors in promoting growth of uterine leiomyomata. Results from immunohistochemical studies would be correlated with results form gene chip studies. We have identified two groups of leiomyomata that are …pathogenetically distinct. Further studies are underway to identify ethnic and morphologic correlates of these two groups. 69. Jianjun Wei, Luis Chiriboga, Masashi Mizuguchi, Herman Yee, Khush Mittal. Expression profile of Tuberin and Some Potential Tumorigenic Factors in 60 Patients with Uterine Leiomyomata. Mod Path 18:179-188, 2005 Wei J, Chiriboga L, Mittal K. Expression profile of the tumorigenic factors in association with tumor size and sex steroid hormone status in uterine leiomyomata. Fertil Steril 84:474?84, 2005 75. Jian-Jun Wei, Xinming Zhang, Luis Chiriboba, Herman Yee, Khush Mittal. Large Uterine Leiomyomata: Spatial Differences in Biological Activity. Fertil Steril. 85:179-87, 2006 76. Jian-Jun Wei, Melamed J, Luis Chiriboba, Herman Yee, Khush Mittal. Ethnic Differences in Expression of the Dysregulated Proteins in Uterine Leiomyomata. Hum Reprod. 21:57-67, 2006 3. Precursor lesions for Uterine Leiomyosarcoma: While precancerous lesions in the carcinomas are well described (for example intraductal carcinoma of breast), similar premalignant lesions are not widely recognized for sarcomas. I have identified possible precursor lesions to uterine leiomyosarcoma (cellular and atypical leiomyoma) that can be frequently found on sections of leiomyosarcoma on careful examination. Further studies are underway to delineate the molecular changes in these various areas to determine if these benign looking areas represent precursor lesions for leiomyosarcomas or leiomyosarcomas that have differentiated into more mature areas. 4. Ki-67 in diagnostic Cervical Pathology: MIB-1 is a monoclnal antibody to Ki-67 antigen. It works well in formalin fixed tissues. We have used MIB-1 immunohistochemistry to distinguish uterine cervical benign and reactive lesions from condylomas and dysplasias. We have found it very useful for differentiating atrophic changes that can mimic dysplasia, from true dysplasia. We have shown that MIB-1 expression is also useful in differentiating leiomyosarcomas from leiomyomas and smooth muscle tumors of uncertain malignant potential.

Mittal K, Mesia A, Demopoulos R. MIB-1 expression is useful in distinguishing dysplasia from atrophy in elderly women. Int J Gynecol Pathol 18:122-4, 1999.

Mittal K. Utility of proliferation associated marker MIB-1 in evaluating lesions of the uterine cervix. Adv Anat Pathol 6:177-185, 1999.

Mittal K. Utility of MIB-1 in evaluating cauterized cone biopsy margins. Int J Gynecol Pathol 18:211-214, 1999.