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Class III ß-Tubulin Overexpression Is a Marker of Poor Clinical Outcome in Advanced Ovarian Cancer Patients

Authors' Affiliations: ¹ Department of Oncology, Catholic University, Campobasso, Italy and ² Institute of Human Pathology, ³ Gynecologic Oncology Unit, Catholic University, Rome, Italy

Requests for reprints: Gabriella Ferrandina, Gynecologic Oncology Unit, Catholic University of the Sacred Heart, Largo Agostino Gemelli, 8, 00168 Rome, Italy. Phone/Fax: 39-06-35508736; E-mail: gabriella.ferrandina{at}libero.it.

Purpose: Overexpression of ß III tubulin has been involved in paclitaxel resistance in several experimental models. We investigated the role of ß III tubulin as predictor of clinical outcome in ovarian cancer patients given platinum/paclitaxel treatment. We also investigated whether ß 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 ß-tubulin antibody.

Results: ß III Tubulin immunoreaction was observed in 51 of 62 (82.2%) cases. ß III Tubulin positivity was neither associated with clinicopathologic variables nor with pathologic response to chemotherapy. Significantly lower percentages of ß 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 ß III tubulin expression showed a worse overall survival with respect to cases with low ß III tubulin expression (median overall survival, 25 versus 46 months; P = 0.002). Multivariate analysis showed that high content of ß III tubulin remains independently associated with a worse prognosis.

Conclusions: Assessment of ß III tubulin could be useful to identify poor prognosis ovarian cancer patients candidates to more aggressive and/or targeted therapy.

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