Faculty Bibliography

Synchrotron FTIR maps, focal plane array and linear array images recorded of 4 mu m cervical biopsy sections from the surface epithelium and glandular endometrium are compared in terms of spatial resolution and applicability to the clinical environment. Synchrotron FTIR maps using a 10 mu m aperture appear to provide a better spatial resolution capable of discerning single nuclei in the tissue matrix. Unsupervised hierarchical cluster analysis performed on the synchrotron, focal plane array and linear array data in the 1700-1400 cm(-1) region show very similar clusters and mean-extracted spectra, demonstrating the robustness of FTIR microscopy and UHCA in the analysis of tissue sections. Maps recorded with the focal plane array using a conventional globar source take one-fortieth of the time but the spatial resolution precludes true single cell analysis in the tissue matrix. The high spatial resolution achieved with the synchrotron shows potential as a gold standard for FTIR diagnosis of cervical samples.

Invasion into surrounding brain tissue is a fundamental feature of gliomas and the major reason for treatment failure. The process of brain invasion in gliomas is not well understood. Differences in gene expression and/or gene products between invading and noninvading glioma cells may identify potential targets for new therapies. To look for genes associated with glioma invasion, we first employed Affymetrix microarray Genechip((R)) technology to identify genes differentially expressed in migrating glioma cells in vitro and in invading glioma cells in vivo using laser capture microdissection. We observed upregulation of a variety of genes, previously reported to be linked to glioma cell migration and invasion. Remarkably, major histocompatiblity complex (MHC) class I and II genes were significantly downregulated in migrating cells in vitro and in invading cells in vivo. Decreased MHC expression was confirmed in migrating glioma cells in vitro using RT-PCR and in invading glioma cells in vivo by immunohistochemical staining of human and murine glioblastomas for beta2 microglobulin, a marker of MHC class I protein expression. To the best of our knowledge, this report is the first to describe the downregulation of MHC class I and II antigens in migrating and invading glioma cells, in vitro and in vivo, respectively. These results suggest that the very process of tumor invasion is associated with decreased expression of MHC antigens allowing glioma cells to invade the surrounding brain in a 'stealth'-like manner.Laboratory Investigation (2005) 85, 328-341, advance online publication, 31 January 2005; doi:10.1038/labinvest.3700233

OBJECTIVE: To use tissue microarray in combination with dendrogram cluster analysis to characterize some potential tumorigenic factors in association with tumor size and sex steroid hormone status in uterine leiomyomata. DESIGN: Expression analysis of 21 selected potential tumorigenic factors in 60 patients with uterine leiomyomata. SETTING: University clinical research laboratory. PATIENT(S): Hysterectomy specimens from 60 patients with uterine leiomyomata of different ages and tumor sizes. INTERVENTION(S): Tissue cores from normal myometrium and leiomyomata were examined by immunohistochemistry. MAIN OUTCOME MEASURE(S): Semiquantitative immunointensity was scored and analyzed by net gain and loss between normal myometrium and leiomyomata and integrated into dendrogram cluster tree view. RESULT(S): We found that upregulation of estrogen and progesterone receptors was reverse associated with tumor size. Upregulation of some factors (HMGA2, sex steroid receptor cofactors, proteins in insulin pathway, and CD24) were identified in a group of patients in their later forties, were associated with large fibroids, and were weakly affected by the SSH status (illustrated by endometrial phases and menopause). Downregulation of tuberin and glucocorticoid receptor was mostly isolated in a second group of women at their late reproductive age. CONCLUSION(S): Analyses of the sex steroid hormone receptors and the nonsex steroid hormone factors in leiomyomata and the matched myometrium showed different expression patterns in different tumor sizes and patients' ages. A group of patients in their late forties with the larger leiomyomata contributes largely by upregulation of nonsex steroid hormone factors. Adenomyosis is a protective factor preventing large leiomyomata