Mesothelin與上皮性卵巢癌病人其化學治療反應的關聯性

目的：上皮性卵巢癌是所有婦科癌症之中死亡率最高的疾病之一。對於上皮性卵巢癌的標準治療方式為盡可能最大範圍的減積手術，再追加輔助性化學治療。臨床上在處理上皮性卵巢癌的病人時常常會因為腫瘤對化學治療容易產生抗藥性，導致預後不佳。Mesothelin－一種由間質細胞(mesothelial cell)分泌的醣蛋白，最早是由間質細胞、間質細胞瘤，以及卵巢癌細胞中所發現。Mesothelin確切的功能，至今仍無法得知。這個研究的目的，在於評估上皮性卵巢癌組織中mesothelin表現的多寡，是否會和臨床上病人對化學治療的反應有所相關。方法：我們總共收集了九十八名上皮性卵巢癌的病人，他們都接受手術及術後輔助性化學治療。如果是進展性疾病，或是在完成化學治療後的六個月內復發者，我們將這些病人定義為對化學治療具抗藥性組；病人如果在完成化學治療後，大於六個月後才復發，以及尚未復發者，我們將這些病人定義為對化學治療具敏感性組。我們收集這些病人臨床以及病理學上的因子，採用quantitative competitive RT-PCR(QC RT-PCR)以及real-time quantitative RT-PCR(RTQ RT-PCR)方法來測量卵巢癌組織中mesothelin基因的表現量，並與臨床資料及病人的預後做相關分析。結果：在卵巢癌的組織中，對化學治療具抗藥性的一組，比對化學治療具敏感性的一組，其mesothelin的表現量較高(p<0.05)。此外，分化較差的腫瘤，也比分化較佳的腫瘤表現出更多的mesothelin(p<0.05)。表現過量mesothelin的病人，比表現正常量mesothelin的病人，有較短的無病存活期(10.8月 v.s. 20.2月; p<0.05)。此外，在漿液性上皮性卵巢癌的病人之中，表現過量mesothelin的病人，比mesothelin表現量正常的病人，有較短的整體存活期(Log Rank Test: p<0.01)。結論：上皮性卵巢癌組織中，mesothelin表現的多寡，可以用來評估病人對化學治療是否會產生抗藥性。

關鍵字

上皮性卵巢；預後； mesothelin ；化學治療；抗藥性

並列摘要

Objective: Ovarian cancer is one of the leading cause of death among all gynecologic malignancies. The standard treatment of epithelial ovarian cancer (EOC) includes maximally debulking surgery followed by adjuvant chemotherapy. However, resistance to chemotherapy is an important issue while managing patients with EOC. Mesothelin, a secreted glycoprotein, was originally identified on mesothelial cells, mesotheliomas and ovarian cancers. The definite function of mesothelin is still to be clarified. This study is to investigate if the expression levels of mesothelin would correlate with chemotherapeutic response of patients with EOC. Methods: Ninety eight patients with EOC received operation and postoperative adjuvant chemotherapy were enrolled. Patients with progressive disease or with recurrence within 6 months after completion of chemotherapy were defined as resistant group. Patients without recurrence or with recurrence more than 6 months after completion of chemotherapy were defined as sensitive group. Their clinical and pathologic items were recorded. Expression of mesothelin in ovarian cancer tissue was measured by quantitative competitive RT-PCR (QC RT-PCR) and real-time quantitative PCR (RQ-PCR) methods. The results were correlated to clinical data and outcome of these patients. Results: The expression of mesothelin in ovarian cancer tissue was significantly higher in patients of resistant group than in sensitive group (p<0.05). In addition, high grade tumors also expressed higher level of mesothelin than those with low grade tumors (p<0.05 ). Patients with mesothelin over-expression had significantly shorter disease free survival than those with normal expression of mesothelin (10.8 months v.s.20.2 months; p<0.05). Patients with over-expression of mesothelin had a poorer overall survival than those with normal expression of mesothelin in serous type of EOC (Log Rank Test: p<0.01). Conclusions: The expression level of mesothelin in ovarian cancer tissue might be a predictor for the possibility of chemotherapy resistance for patients of EOC.

並列關鍵字

epithelial ovarian cancer ； prognosis ； mesothelin ； chemotherapy ； drug-resistance

參考文獻

2. Rustin GJ. Tumour markers for ovarian cancer. Eur J Cancer 1992;28:2-3.

3. Pfleiderer A. Diagnosis and staging of ovarian cancer. J Cancer Res Clin Oncol 1984;107:81-8.

4. Gonzalez-Diego P, Lopez-Abente G, Pollan M, Ruiz M. Time trends in ovarian cancer mortality in Europe (1955-1993): effect of age, birth cohort and period of death. Eur J Cancer 2000;36:1816-24.

7. Hacker NF, Berek JS, Lagasse LD, Nieberg RK, Elashoff RM. Primary cytoreductive surgery for epithelial ovarian cancer. Obstet Gynecol 1983;61:413-20.

8. Malkasian GD, Jr., Melton LJ, 3rd, O'Brien PC, Greene MH. Prognostic significance of histologic classification and grading of epithelial malignancies of the ovary. Am J Obstet Gynecol 1984;149:274-84.

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Mesothelin與上皮性卵巢癌病人其化學治療反應的關聯性

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