The objective of the study was to evaluate the prognostic effect of p53, Her-2, and EGFR in borderline and epithelial ovarian cancer. Tumor tissue from 85 patients with borderline and 783 patients with epithelial ovarian cancer stage I-IV were analyzed immunohistochemically for p53 positivity and over-expression of Her-2 and EGFR. In the ovarian cancer (OC) group 415 patients (53%) had p53-positive tumors, 272 (35%) had tumors with Her-2 over-expression, and 483 (62%) had over-expression of EGFR. In the OC group the classical prognostic factors (older age, higher FIGO stage, and poorer differentiated stage) had significant prognostic value in both uni- and multivariate analyses. Multivariate analyses in the OC group proved p53 positivity to increase mortality significantly depending on the grade of the tumor. Her-2 likewise increased the risk of mortality significantly in this group depending on the grade of the tumor. EGFR on the other hand did not have any additional prognostic effect in the OC group after adjustment for the classical prognostic and molecular factors was made. In the borderline group Her-2 and EGFR over-expression in combination, adjusted for age and p53, significantly improved the prognosis.

Previous reports have described down-regulation of E-cadherin in trophoblasts differentiating to an invasive phenotype. This study shows the localization of E-cadherin in a prospective design with stereological sampling of fetal and maternal first, second and third trimester tissue. E-cadherin was observed in villous cytotrophoblasts, and in non-proliferating, intermediate trophoblasts (IT) within cell columns and islands in intrauterine, ectopic and partial molar placentas. Highly proliferating IT with cytological atypia in complete molar placentas were also E-cadherin-positive. E-cadherin was present in trophoblasts throughout the anchoring cell columns. Trophoblasts undergoing epithelial mesenchymal transformation (EMT) detaching from the distal cell columns and deeper located single extravillous interstitial trophoblasts (EVT) showed E-cadherin-negative breaches in the cell membrane. Prior to the late second trimester, the relative number of E-cadherin-positive single EMT and EVT differed from the total number of cytokeratin-positive trophoblasts. Intraluminal, endovascular and perivascular trophoblasts adjacent to the maternal vessels were also E-cadherin-positive, but a highly varying pattern was observed at different ages of gestation. Our results indicate a temporary shift in E-cadherin expression in extravillous trophoblasts possessing a migrating and invasive potential. Functional E-cadherin may be restored as trophoblasts aggregate in the decidua and the vessel wall after completion of migration.

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PurposePaclitaxel has a broad spectrum of anti tumor activity and is useful in the treatment of ovarian, breast and lung cancer. Paclitaxel is metabolized in the liver by CYP2C8 and CYP3A4 and transported by Pglycoprotein. The dose limiting toxicity is neuropathy and neutropenia, but the inter-individual variability in toxicity and also survival is large. The main purpose of this study was to investigate the impact of genetic variants in CYP2C8 and ABCB1 on the toxicity and survival. MethodsThe 182 patients previously treated for ovarian cancer with carboplatin and paclitaxel in either the AGO-OVAR-9 or the NSGO-OC9804 trial in Denmark or Sweden were eligible for this study.Genotyping was carried out on formalin fixed tissue. The patients' toxicity profiles and survival data were derived from retrospective data. CYP2C8*3, ABCB1 C1236T, G2677T/A and C3435T were chosen pre hoc for primary analysis; a host of other variants entered an exploratory analysis. ResultsClinical data and tissue was available from a total of 119 patients. Twenty-two single nucleotide polymorphism(SNPs) in 10 genes were determined. Toxicity registration was available from 710 treatment cycles. Primary analysis: no statistical significant correlation was found between CYP2C8*3, ABCB1 C1236T, G2677T/A and C3435T and neutropenia, sensoric neuropathy and overall survival. ConclusionCYP2C8*3 and the ABCB1 SNPs C1236T, G2677T/A and C3435T are not statistically significantly correlated to overall survival, sensoric neuropathy and neutropenia in 119 patients treated for ovarian cancer with paclitaxel/carboplatin.