Purpose: Overexpression of h III tubulin has been involved in paclitaxel resistance in several experimental models. We investigated the role of h III tubulin as predictor of clinical outcome in ovarian cancer patients given platinum/paclitaxel treatment. We also investigated whether h III tubulin expression could be modified after the selective pressure represented by chemotherapy in vivo. Experimental Design: The study was designed to include a series of consecutive ovarian cancer patients with unresectable disease at time of first surgery, who underwent interval debulking surgery with pathologic assessment of response to treatment with platinum/ paclitaxel chemotherapy. Immunostaining was done on formalin-fixed, paraffin-embedded tissue sections from pretreatment and posttreatment tissue biopsies by using the polyclonal rabbit anti^class III h-tubulin antibody. Results: h III Tubulin immunoreaction was observed in 51 of 62 (82.2%) cases. h III Tubulin positivity was neither associated with clinicopathologic variables nor with pathologic response to chemotherapy. Significantly lower percentages of h III tubulin positivity were observed in posttreatment (range, 5-80%; median, 20%) versus pretreatment (range 10-100%; median, 40%) tissue biopsies (P = 0.0011). Cases with high h III tubulin expression showed a worse overall survival with respect to cases with low h III tubulin expression (median overall survival, 25 versus 46 months; P = 0.002). Multivariate analysis showed that high content of h III tubulin remains independently associated with a worse prognosis. Conclusions: Assessment of h III tubulin could be useful to identify poor prognosis ovarian cancer patients candidates to more aggressive and/or targeted therapy.

Cancer stem cells have been isolated from several solid tumors including prostate, colon, liver, breast, and ovarian cancer. Stem cells isolated from nervous system and prostate express CD133 antigen, which is widely used to isolate hematopoietic stem and progenitor cells. The aims of this study were to investigate the expression of the CD133-1 and CD133-2 epitopes in primary ovarian tumors and to biologically characterize CD133(+) ovarian cancer cells, also according to clinicopathologic parameters. Tissue specimens were obtained at primary surgery from 41 ovarian carcinomas; eight normal ovaries and five benign ovarian tumors were also collected. Flow cytometry with monoclonal antibodies against CD133-1 and CD133-2 epitopes was employed. FACS (fluorescence activated cell sorting) analysis enabled the selection of CD133(+) cells, whose epithelial origin was confirmed by immunofluorescence analysis with monoclonal anti-cytokeratin 7. CD133(+) cells gave rise to a 4.7 +/- 0.9-fold larger number of colonies than that documented in CD133(-) population (P < 0.001). Moreover, CD133(+) cells showed an enhanced proliferative potential compared to CD133(-) cells. The percentages of CD133-1- and CD133-2-expressing cells were significantly lower in normal ovaries/benign tumors with respect to those in ovarian carcinoma. Both the percentages of CD133-1- and CD133-2-expressing cells were significantly lower in omental metastases than in primary ovarian cancer (P = 0.009 and 0.007 for CD133-1- and CD133-2-expressing cells, respectively). There seems not to be any difference in the distribution of the percentage of CD133-1- and CD133-2-expressing cells according to clinicopathologic parameters and response to primary chemotherapy. CD133-1 and CD133-2 may be useful in order to select and enrich the population of CD133(+) ovarian tumor cells, which are characterized by a higher clonogenic efficiency and proliferative potential.

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BACKGROUND: In advanced ovarian cancer, maximal efforts have to be attemptedto achieve optimal cytoreduction, as this represents the keystone in the therapeutic management. This large, prospective study aims at investigating the role of computed tomography (CT) scan in predicting the feasibility of optimal cytoreduction in ovarian cancer. METHODS: A total of 195 consecutive patients with clinical/radiographic suspicion of advanced ovarian/peritoneal cancer were enrolled at the Gynecologic Oncology Unit, Catholic University of Rome and Campobasso, Italy. Preoperative CT scans were performed with a high-speed scanner (CT Hi Speed Nx/i Pro; 2-slice; GE Medical System). All patients underwent standard laparotomy, and maximal surgical effort was attempted. The following CT parameters were used: peritoneal thickening, peritoneal implants 42 cm, bowel mesentery involvement, omental cake, pelvic sidewall involvement and/or hydroureter, suprarenal aortic lymph nodes 41 cm, infrarenal aortic lymph nodes 42 cm, superficial liver metastases 42 cm and/or intraparenchimal liver metastases any size, large volume ascites (4500 ml). Clinical data included were age, Ca125 serum levels, and ECOG-PS. Radiographic and clinical features exhibiting a specificity 475%, a positive and negative predictive value 450%, an accuracy 460% in predicting surgical outcome were assigned a point value of 2. With this scoring system, a predictive index (PI) was calculated for each patient. RESULTS: The PI scores ranged from 0 to 6, and from 0 to 8, in Model 1 (including only radiographic parameters) and in Model 2 (including radiographic and clinical data). The AUC was 0.78 þ 0.035 in Model 1, and 0.81 þ 0.031 in Model 2. Therefore, the addition of ECOG-PS data led to the improvement of the diagnostic performances (z ¼ 2.41, P-value o0.05). CONCLUSIONS: Computed scan still represents a valid tool to predict ovarian cancer optimal cytoreduction; the predictive ability of a CT scan-based model is improved by integrating ECOG-PS data.

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