Stage IA vs. IB endometrial stromal sarcoma: does the new staging system predict survival?

OBJECTIVE: To determine the correlation of the new FIGO staging system with survival in stage I patients with low-grade and high-grade endometrial stromal sarcomas. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Kaplan-Meier log rank and Cox proportional hazards models were used for survival analysis and to identify possible predictors for survival. RESULTS: The identified cohort included 464 women, 310 (67%) low-grade endometrial stromal sarcoma, 96 (21%) high-grade endometrial stromal sarcoma, and 58 (12%) unclassified endometrial stromal sarcoma. Among low-grade and high-grade endometrial stromal sarcomas, there was no significant demographic or clinico-pathologic difference between stages IA and IB. The 5-year overall survival was worse in high-grade endometrial stromal sarcoma than low-grade endometrial stromal sarcoma (45.4% vs. 97.2%, p<0.001). The difference in 5-year overall survival among women with low-grade endometrial stromal sarcoma between stages IA and IB was significant (100% vs. 93.5%, p=0.003), but not among women with high-grade endometrial stromal sarcoma (51.4% vs. 43.5%, p=0.27). Although age (p=0.001), race (p=0.005), and stage (p=0.004) were all significant prognostic factors in low-grade endometrial stromal sarcoma, only cervical involvement (p=0.02) was a significant predictor in high-grade endometrial stromal sarcoma. CONCLUSION: The new staging system is appropriate for risk stratification in low-grade endometrial stromal sarcoma. The prognosis in high-grade endometrial stromal sarcoma seems to be most influenced by the presence of cervical involvement and not by tumor size as the staging criteria would suggest.

The activated macrophage colony-stimulating factor (CSF-1) receptor as a predictor of poor outcome in advanced epithelial ovarian carcinoma.

OBJECTIVE: We have previously shown that the macrophage colony-stimulating factor receptor (CSF-1R) and its ligand, CSF-1, together predict poor prognosis in epithelial ovarian carcinoma. The activated or phosphorylated form of CSF-1R (CSF-1Rphos) has been associated with enhanced invasive and metastatic potential. Our goal is to correlate CSF-1Rphos with known prognostic factors and to determine its role in predicting outcome in advanced ovarian cancer. METHODS: One hundred forty-two primary and forty-seven metastatic epithelial ovarian tumors from 98 patients were immunohistochemically stained using antibodies PY809 and PY723 against their respective tyrosine residues associated with local invasiveness and metastasis. chi2 analysis was used to correlate CSF-1Rphos staining and previously studied prognosticators within each group. Kaplan-Meier curves of survival were comparedusing the log-rank test with significance of P < 0.05. RESULTS: Forty-seven and nine-tenths percent (68/142) of primary tumors and forty-eight and nine-tenths percent (23/47) of metastatic tumors stained positive for PY809 and PY723, respectively. The PY809+ group was strongly associated with CSF-1R (P = 0.015) as was the PY723+ group (P = 0.025) in its respective subset. CSF-1Rphos by itself was not a predictor of survival or disease-free interval (DFI) in either the primary or metastatic group. However, when combined with CSF-1R in the metastatic group, the two together predicted worse survival (P = 0.007) and decreased DFI (P = 0.011). CONCLUSIONS: Phosphorylated tyrosine kinase receptors are detectable in a significant number of ovarian tumors. Staining strongly correlates with CSF-1R. PY723+ metastases coexpressing CSF-1R portend a highly significant decrease in survival and increased risk of recurrence which may serve to identify high-risk ovarian cancer patients.

Induction of cell-cycle arrest in cervical cancer cells by the human immunodeficiency virus type 1 viral protein R.

OBJECTIVE: To determine the ability of the human immunodeficiency virus type 1 (HIV-1) gene vpr to induce cell-cycle arrest in cervical cancer cells with or without human papillomavirus (HPV) type 16 E6 or E7 expression. METHODS: High- and low-level expression vectors for vpr (designated pVPR(HIGH) and pVPR(LOW), respectively) were used in conjunction with HPV-16 E6 or E7 vectors to transfect HPV-negative C33A cervical cancer cells. Vpr expression vectors encode a cell surface marker gene, murine Thy-1, for specific detection of transfected cells. Dual staining for the surface molecule Thy-1 and DNA content was used to determine cell-cycle profile and G2-phase arrest. RESULTS: C33A cells not expressing HPV-16 E6 showed some but not maximal G2-phase arrest when transfected with pVPR(HIGH) alone (43.2% of cells in the G2 phase). Addition of HPV-16 E6 or E6 plus E7 to pVPR(HIGH) substantially increased the percentages of cells in the G2 phase (51.3% and 53.0%, respectively). Cotransfection with pVPR(HIGH) and HPV-16 E7 did not increase significantly the percentage of cells in the G2 phase compared with pVPR(HIGH) alone (40.6% versus 43.2%). In transfections involving pVPR(LOW), a slight degree of G2-phase arrest was observed when Vpr was expressed alone (29.0% of cells in the G2 phase) or in cotransfection with HPV-16 E7 (33.2% of cells), and G2-phase arrest was augmented with the addition of HPV-16 E6 (41.7%) or E6 plus E7 (45.7%). CONCLUSION: Cervical cancer cells are susceptible to cell-cycle arrest induced by HIV-1 vpr. This effect is exacerbated by coexpression of HPV-16 E6, although E6 alone is incapable of inducing any detectable G2-phase arrest, suggesting that E6 and VPR share links in cell-cycle signaling pathways.