Showing papers by "John I. Risinger published in 2006"

Racial disparity in survival among patients with advanced/recurrent endometrial adenocarcinoma: a Gynecologic Oncology Group study.

Abstract: BACKGROUND. Previous studies have reported shorter survival of black women compared with white women who had advanced/recurrent endometrial cancer. It has been suggested that this may reflect racially based differences in treatment. METHODS. The authors retrospectively reviewed data from 169 black women and 982 white women with International Federation of Gynecologic Oncology (FIGO) Stage III, Stage IV, or recurrent endometrial carcinoma who were participants in 1 of 4 Gynecologic Oncology Group randomized treatment trials of doxorubicin alone or combined with paclitaxel and/or cisplatin. Demographic, histologic, treatment, and outcome data were analyzed to estimate survival, and between-group comparisons were performed. RESULTS. The pooled data revealed that black women were more likely to have papillary serous histology (P < .001), Stage IV disease (P < .001), and higher tumor grade (P < .001) compared with white women, and survival was worse among black women than among white women (median survival, 10.6 months vs. 12.2 months, respectively; P < .001). A Cox proportional hazards regression analysis that was adjusted for performance status, disease stage, tumor histology, tumor grade, and treatment demonstrated worse survival for black women (hazards ratio, 1.26, 95% confidence interval, 1.06–1.51; P = .010). CONCLUSIONS. The data from a large group of women with advanced/recurrent endometrial cancer suggested that a racial disparity in survival persists, despite the finding that black women and white women received similar treatment. Although the causes of racial disparity in endometrial cancer remain to be elucidated, socioeconomic, biologic, and cultural factors should be investigated to identify the etiologic origins of this multifactorial healthcare problem. Cancer 2006. Published 2006 by the American Cancer Society

Prediction of lymph node metastasis in patients with endometrioid endometrial cancer using expression microarray.

Abstract: Purpose: To characterize the gene expression profiles of endometrioid endometrial cancers associated with lymph node metastasis in an effort to identify genes associated with metastatic spread. Experimental Design: Tumors from 41 patients with endometrioid endometrial cancer grossly confined to the uterine cavity were evaluated. Positive lymph nodes were noted in 12 of 41 patients. RNA was analyzed for gene expression using the Affymetrix HG133A and HG133B GeneChip set, representing 45,000 array features covering >28,000 UniGene clusters. Data analysis was done using multidimensional scaling, binary comparison, and hierarchical clustering. Gene expression for several differentially expressed genes was examined using quantitative PCR. Results: Gene expression data was obtained from 30,964 genes that were detected in at least 5% of the cases. Supervised analysis of node-positive versus node-negative cases indicated that 450 genes were significantly differentially expressed between the two classes at P P CDC2 and MAD2L1 , which have previously been described in association with lymph node metastasis in other cancer types. The ZIC2 zinc finger gene was overexpressed in endometrial cancers with positive nodes versus those with negative nodes. Conclusion: Gene expression profiling of the primary tumors in patients with endometrioid endometrial cancers seems promising for identifying genes associated with lymph node metastasis. Future studies should address whether the status of nodal metastasis can be determined from the expression profiles of preoperative tissue specimens.

Characterization of an antibody that can detect the Kai1/CD82 murine metastasis suppressor

Abstract: BACKGROUND Kai1, also known as CD82, is a member of the tetraspanin family (TM4SF). The human homolog, KAI1, is an activation antigen of T-cells and is a metastasis suppressor for prostate and other cancers. Little is known about the mouse protein because of the lack of antibody reagents. METHODS Peptide immunized rabbits were used to generate polyclonal antibody to Kai1. The antibody was analyzed using immunoblotting, flow cytometry, and immunohistochemistry. RESULTS This antibody specifically recognizes murine Kai1 protein, crossreacts with rat Kai1 but not with human KAI1. The normal tissue distribution of this protein in mice is shown to be similar to that of the human homolog. Interestingly, mouse prostatic epithelium showed differential expression within the lobes. CONCLUSION This antibody, the first described that can specifically detect murine Kai1/CD82, should be very useful in addressing the mechanism of action of Kai1 in metastatic suppression. Prostate 66:567–577, 2006. © 2005 Wiley-Liss, Inc.

Mitotic spindle protein aspm as a diagnostic marker for neoplasia and uses therefor

Abstract: The invention features diagnostic and therapeutic methods and compositions featuring ASPM proteins and nucleic acid molecules whose expression is increased in neoplastic tissues.

Gene expression analysis of tumor infiltrating lymphocyte markers in endometrial cancers indicates no significant increases in those cases with microsatellite instability.

Abstract: Microsatellite instability (MSI) is seen in many cancers and is the result of either a germline or somatic defect in the DNA mismatch repair system. Microsatellite instability is common in endometrial cancers occurring in about 25% of cases with endometrioid histology. Tumor infiltrating lymphocytes (TIL) are more prominent in colorectal cancer cases with MSI. The presence of increased TIL is associated with increased survival in these colorectal cancers, and is suggested as one possible mechanism to explain the increased survival rates in colorectal cancer patients with MSI positive cancers. Some degree of evidence indicates that increased TIL is also predictive of increased survival in endometrial cancer. The relative levels and states of activation of TIL in endometrial cancers with and without MSI has not been explored. Our previous data indicates that global gene expression patterns from MSI and non-MSI endometrial cancers are distinct, however TIL markers were not over-represented on statistically relevant gene lists that distinguish these groups. We further examined these pre-existing microarray data by directly querying transcripts present in the T-cell gene ontology (GO) group. No significant differences were observed between MSI and microsatellite stable (MSS) groups. Finally we directly examined a set of T-cell marker transcripts previously utilized to define increased activated and cytotoxic TIL in MSI positive colorectal cancers. Whereas colorectal cancers with MSI have been previously demonstrated to contain higher ratios of CD8/CD3 message levels we observed no difference in endometrial cancers. In addition, levels of CD3 indicated no increases in TIL in MSI positive cases and 2 markers of activation, granzyme B and IL-2R were not different in MSI positive and negative cancers. These data indicate that significant differences in TIL derived transcripts do not occur between endometrioid endometrial cancers with and without microsatellite instability.