Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, North 15 West 7 Kita-Ku, Sapporo, Japan.
Pathol Oncol Res. 2010 Sep;16(3):345-52. doi: 10.1007/s12253-009-9235-0. Epub 2010 Jan 8.
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.
簇集蛋白（clusterin）是一种抗凋亡分子，其过表达已被报道可诱导多种癌细胞类型对化疗产生耐药性。本研究旨在评估簇集蛋白表达对预测接受新辅助化疗的浸润性宫颈癌患者对铂类为基础的新辅助化疗的反应和生存的意义，并接受根治性子宫切除术。从 1994 年至 2007 年，在北海道大学医院和群马大学医院接受根治性子宫切除术的 46 例浸润性宫颈癌患者在新辅助化疗前获得了活检标本。通过免疫组织化学分析簇集蛋白的表达。评估结果与几种临床病理因素有关。通过 Kaplan-Meier 曲线和对数秩检验进行生存分析。通过多变量 Cox 回归分析确定独立的预后因素。簇集蛋白蛋白主要存在于宫颈癌细胞质中。新辅助化疗前宫颈癌组织中簇集蛋白的表达与分析的因素中化疗反应不良显著相关。对预后因素的单因素分析显示，化疗反应（p=0.01）、淋巴结转移（p=0.02）和簇集蛋白表达（p=0.02）与生存有关。多因素分析显示，淋巴结转移（p=0.03）和簇集蛋白表达（p=0.03）是宫颈癌患者生存的独立预后因素。我们得出结论，簇集蛋白表达可能是预测接受新辅助化疗和根治性子宫切除术的宫颈癌患者对铂类为基础的化疗反应和生存的新的分子标志物。
