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

• Published in: Clinical cancer research 2006-05, Vol.12 (9), p.2774-2779
• Main Authors: FERRANDINA, Gabriella, ZANNONI, Gian Franco, MARTINELLI, Enrica, PAGLIA, Amelia, GALLOTTA, Valerio, MOZZETTI, Simona, SCAMBIA, Giovanni, FERLINI, Cristiano
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic agents; Biological and medical sciences; Disease Progression; Female; Female genital diseases; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Middle Aged; ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Ovarian Neoplasms - surgery; Pharmacology. Drug treatments; prognosis; Retrospective Studies; Survival Analysis; Tubulin - analysis; Tubulin - genetics; Tumors; β III tubulin
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-2715

Purpose: Overexpression of β III tubulin has been involved in paclitaxel resistance in several experimental models. We investigated the role of β III tubulin as predictor of clinical outcome in ovarian cancer patients given platinum/paclitaxel treatment. We also investigated whether β 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 β-tubulin antibody. Results: β III Tubulin immunoreaction was observed in 51 of 62 (82.2%) cases. β III Tubulin positivity was neither associated with clinicopathologic variables nor with pathologic response to chemotherapy. Significantly lower percentages of β 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 β III tubulin expression showed a worse overall survival with respect to cases with low β III tubulin expression (median overall survival, 25 versus 46 months; P = 0.002). Multivariate analysis showed that high content of β III tubulin remains independently associated with a worse prognosis. Conclusions: Assessment of β III tubulin could be useful to identify poor prognosis ovarian cancer patients candidates to more aggressive and/or targeted therapy.