Diagnostic accuracy of magnetic resonance imaging in endometrial cancer.

OBJECTIVES: The objectives of this study were to investigate the accuracy of magnetic resonance imaging (MRI) in predicting the depth of myometrial invasion in the preoperative assessment of women with endometrial cancer and to quantify the impact of MRI as an adjunct to predicting patients requiring full surgical staging. METHODS: This was a diagnostic accuracy study of prospective cases in conjunction with STARD guidelines using collected data from a tumor board within a cancer network. Consecutive series of all endometrial cancers in Northern Ireland over a 21-month period was discussed at the Gynaecological Oncology Multidisciplinary Team/tumor board meeting. This study concerns 183 women who met all the inclusion criteria. Main outcome measure was the correlation between the depth of myometrial invasion suggested by preoperative MRI study and the subsequent histopathological findings following examination of the hysterectomy specimen. Secondary end point was how MRI changed management of women who required surgery to be performed at a central cancer center. RESULTS: For the detection of outer-half myometrial invasion, overall sensitivity of MRI was 0.73 (95% confidence interval [CI], 0.59-0.83), and specificity was 0.83 (95% CI, 0.76-0.89). The positive predictive value was 0.63 (95% CI, 0.50-0.74), and negative predictive value was 0.89 (95% CI, 0.82-0.93). Positive likelihood ratio was 4.35 (95% CI, 2.87-6.61), and negative likelihood ratio was 0.33 (95% CI, 0.21-0.52). Magnetic resonance imaging improved the sensitivity and negative predictive value of endometrial biopsy alone in predicting women with endometrial cancer who require full surgical staging (0.73 vs 0.65 and 0.80 vs 0.78, respectively). CONCLUSIONS: Preoperative pelvic MRI is a moderately sensitive and specific method of identifying invasion to the outer half of myometrium in endometrial cancer. Addition of MRI to preoperative assessment leads to improved preoperative assessment, triage, and treatment.

Properties of SEPT9 isoforms and the requirement for GTP binding.

Members of the evolutionarily conserved septin family of genes are emerging as key components of several cellular processes including membrane trafficking, cytokinesis, and cell-cycle control events. SEPT9 has been shown to have a complex genomic architecture, such that up to 15 different isoforms are possible by the shuffling of five alternate amino termini and three alternate carboxy termini. Genomic and transcriptional alterations of SEPT9 have been associated with neoplasia. The present study has used a Sept9-specific antibody to determine the pattern of isoform expression in a range of tumour cell lines. Western blot analysis indicated considerable variation in the relative amounts and isoform content of Sept9. Immunofluorescence studies showed a range of patterns of cytoplasmic localization ranging from mainly particulate to mainly filamentous. Expression constructs were also generated for each amino terminal isoform to investigate the patterns of localization of individual isoforms and the effects on cells of ectopic expression. The present study shows that the epsilon isoform appears filamentous in this overexpression system while the remaining isoforms are particulate and cytoplasmic. Transient transfection of individual constructs into tumour cell lines results in cell-cycle perturbation with a G2/M arrest and dramatic growth suppression, which was greatest in cell lines with the lowest amounts of endogenous Sept9. Similar phenotypic observations were made with GTP-binding mutants of all five N-terminal variants of Sept9. However, dramatic differences were observed in the kinetics of accumulation of wild-type versus mutant septin protein in transfected cells. In conclusion, the present study shows that the expression patterns of Sept9 protein are very varied in a panel of tumour cell lines and the functional studies are consistent with a model of septin function as a component of a molecular scaffold that contributes to diverse cellular functions. Alterations in the levels of Sept9 protein by overexpression of individual isoforms can clearly perturb cellular behaviour and may thus provide a mechanistic explanation for observations of deranged septin expression in neoplasia.