Clinical and prognostic value of the presence of irregular giant nuclear cells in pT1 ovarian clear cell carcinoma.

In the early stages of epithelial ovarian cancer, histopathological grading is important. However, the grading of ovarian clear cell carcinoma (OCCC) remains controversial. We aimed to identify irregular giant nuclear cells (IGNCs) by a simple method in clinical practice, and to evaluate the prognostic value of IGNCs in pT1 OCCC. Eighty-seven pT1 OCCC patients who underwent initial surgery at Jikei University Kashiwa Hospital, Chiba, Japan, were retrospectively assessed. Paraffin-embedded tissue sections (PTSs) stained with hematoxylin and eosin were reviewed. Giant nuclear cells (GNCs) were defined as cells with a nuclear length of more than twice the median nuclear length. GNCs with irregular nuclear circumferences were defined as IGNCs. Cases where one or more GNCs existed and where IGNCs accounted for >10% of the GNCs were classified as IGNC-positive. We also attempted to identify IGNCs on touch imprint cytology smears (TICSs). Among the 87 cases, 68 were IGNC-negative and 19 were IGNC-positive. The 5-year disease-free and overall survival rates were 88.9% and 90.3% in the total patients, 98.3% and 100% in the IGNC-negative group, and 59.7% and 62.0% in the IGNC-positive group, respectively. These survival rates were significantly lower in the IGNC-positive group than in the IGNC-negative group (adjusted hazard ratio = 14, 95% confidence interval = 2.7-124 and adjusted hazard ratio = 25, 95% confidence interval = 2.9-768, respectively). Prognostic differences were not identified for other factors. IGNC identification on 28 available TICSs predicted IGNC identification on PTSs (sensitivity = 50.0%, specificity = 100%, P = 0.007). The presence of IGNCs has clinical and prognostic value for pT1 OCCC.

Characterization of two independent, exposure-time dependent paclitaxel-resistant human ovarian carcinoma cell lines.

This experiment was conducted to address the question of whether acquired paclitaxel resistance is dependent upon whether it is given as a single brief exposure or as a long-term exposure. PX2 and PX24 were established from 2008 human ovarian cancer cells by 2-h single exposure or 24-h continuous exposure to paclitaxel. PX2 acquired paclitaxel resistance faster than PX24 by twofold. Drug resistant pattern was exposure-time dependent. In 2-h exposure, PX2 showed 53.86 ± 4.96 (mean ± standard deviation [SD]) fold paclitaxel resistance while PX24 showed 9.51 ± 1.01 fold resistance (P = 0.002). In 24-h exposure, PX2 showed 2.31 ± 0.3 fold paclitaxel resistance while PX24 showed 28.17 ± 0.98 fold resistance (P = 0.040). PX2 and PX24 acquired cross-resistance to docetaxel and SN38 and the resistance degrees were significantly higher in PX2 than PX24. They displayed approximately twofold cisplatin collateral sensitivity. PX24 also displayed sensitivity to other platinum drugs, oxaliplatin and ZD0473, whereas PX2 acquired significant resistance to both of them. Although differential tubulin-isotype expressions were noted among 2008, PX2 and PX24, they were not significant. In electron microscopy, prominent, densely stained lysosomes were observed more in the resistant cells than 2008. Two independent, exposure-time dependent paclitaxel-resistant human ovarian carcinoma cell lines were established. Understanding the characteristics of the differential resistance pattern could be clinically beneficial for the selection of second line chemotherapy for relapsed ovarian cancer.