title: Clusterin expression inversely correlates with chemosensitivity and predicts poor survival in patients with locally advanced cervical cancer treated with cisplatin-based neoadjuvant chemotherapy and radical hysterectomy.
abstract: Overexpression of clusterin, an antiapoptotic molecule, has been reported to induce resistance to chemotherapy in a variety of cancer cell types. The aim of this study was to evaluate the significance of clusterin expression to predict response to platinum-based neoadjuvant chemotherapy and survival of patients with invasive cervical cancer who subsequently underwent radical hysterectomy. Biopsy specimens of invasive cervical cancer before neoadjuvant chemotherapy were obtained from 46 patients who subsequently underwent radical hysterectomy at Hokkaido University Hospital and Gunma University Hospital from 1994 to 2007. The expression of clusterin protein was analyzed by immunohistochemistry. Findings were evaluated in relation to several clinicopathological factors. Survival analyses were performed by the Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis. Clusterin protein was mainly present in the cytoplasm of cervical cancer cells. The expression of clusterin protein in cervical cancer tissues before neoadjuvant chemotherapy was significantly related to poor response to chemotherapy among factors analyzed. Univariate analysis on prognostic factors showed that response to chemotherapy (p = 0.01), lymph node metastasis (p = 0.02), and clusterin expression (p = 0.02) were related to survival. Multivariate analysis revealed that lymph node metastasis (p = 0.03), and clusterin expression (p = 0.03) were independent prognostic factors for survival of cervical cancer patients. We conclude that clusterin expression could be a new molecular marker to predict response to platinum-based chemotherapy and survival of patients with cervical cancer treated with neoadjuvant chemotherapy and radical hysterectomy.
authors.affiliation: Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, North 15 West 7 Kita-Ku, Sapporo, Japan. watarih@med.hokudai.ac.jp
authors.forename: Hidemichi
authors.initials: H
authors.lastname: Watari
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanuma
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ohta
authors.forename: Mohamed Kamel
authors.initials: MK
authors.lastname: Hassan
authors.forename: Takashi
authors.initials: T
authors.lastname: Mitamura
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Hosaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Minegishi
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sakuragi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002945:Cisplatin / Q000627:therapeutic use; D051152:Clusterin / Q000096:biosynthesis*; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy*
chemical_list: D014408:Biomarkers, Tumor; D051152:Clusterin; D002945:Cisplatin