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MMAC肿瘤抑制基因在卵巢子宫内膜异位症和卵巢腺癌中的表达。

MMAC tumor supressor gene expression in ovarian endometriosis and ovarian adenocarcinoma.

作者信息

Cirpan T, Aygul S, Terek M C, Kazandi M, Dikmen Y, Zekioglu O, Sagol S

机构信息

Department of Obstetrics and Gynecology, Ege University Faculty of Medicine, Izmir, Turkey.

出版信息

Eur J Gynaecol Oncol. 2007;28(4):278-81.

PMID:17713092
Abstract

OBJECTIVE

The aim of this study was to investigate the role of MMAC1 protein in the relationship between ovarian endometriosis and clear cell and endometrioid-type ovarian adenocarcinomas.

METHODS

A total of 63 subjects who underwent surgery for a pelvic tumoral mass, 30 of whom were diagnosed with grade 1 to 3 ovarian adenocarcinoma and 33 of whom were diagnosed with grade 1 to 4 endometriosis during histopathological examination were included in this study. The mean age for subjects with ovarian endometrioid type adenocarcinoma was 51.8 +/- 12.4, whereas the mean age for subjects with ovarian clear cell type adenocarcinoma was 59.5 +/- 13.7. Ovarian carcinomas were graded in accordance with the FIGO 1989 grading system. The mean age for subjects with endometriosis was 37 +/- 11.9. New sections were obtained from paraffin blocks in the archives of Ege University, School of Medicine, Department of Pathology onto lysinated slides and immunohistochemical staining by using mouse monoclonal antibody (MMAC1, 28H6 clone, Novocastra, UK) as MMAC antibody was applied in order to determine MMAC1 protein. Brown staining on the nucleus was considered as positive immunoreactivity. Immunoreactive staining was evaluated as percentage staining over the whole preparative.

RESULTS

Of the 63 subjects included in the immunohistochemical study, ovarian endometrioid adenocarcinoma was identified in 18 subjects, while 12 subjects were diagnosed with ovarian clear cell adenocarcinoma and 33 subjects with ovarian endometriosis. No significant relationships were observed between age and MMAC immune staining in the ovarian endometrioid adenocarcinoma (r = -0.41, p = 0.08) and ovarian endometriosis (r = 0.12, p = 0.50) groups, whereas a significant relationship was observed in the ovarian clear cell adenocarcinoma group (r = 0.631, p = 0.02). No significant relationships were observed between CA125 levels and MMAC immune staining in the ovarian endometrioide adenocarcinoma (r = 0.056, p = 0.82), ovarian endometriosis (r = 0.21, p = 0.36) and ovarian clear cell adenocarcinoma (r = 0.363, p = 0.24) groups. No correlations were observed between endometriosis stages and the MMAC immune staining (r = -0.17, p = 0.92). There was no correlation between mean diameter of endometrioma and MMAC immune staining (r = -0.230, p = 198). Mean endometrioma diameter was 5.7 +/- 3.5 (1-15.5). No correlations were detected between MMAC immune staining and ovarian endometrioide adenocarcinoma or ovarian clear cell adenocarcinoma stage (r = -0.22, p = 0.37; r = 0.44, p = 0.14, respectively). No significant relationships with respect to MMAC immune staining were detected between the endometriosis and ovarian clear cell adenocarcinoma groups (p = 0.05) and between the ovarian clear cell adenocarcinoma and ovarian endometrioid adenocarcinoma groups (p = 0.27). A significant relationship with respect to MMAC immune staining was observed between ovarian endometrioide adenocarcinoma and endometriosis groups (p = 0.001).

CONCLUSION

Immunohistochemical determination of MMAC defective protein expressions could be considered for utilization as a new, simple and useful technique in determination of endometriosis patients with increased risk of malignant transformation, patients where early surgical treatment would be necessary and patients that should be subjected to follow-up controls with a higher frequency.

摘要

目的

本研究旨在探讨MMAC1蛋白在卵巢子宫内膜异位症与透明细胞型及子宫内膜样型卵巢腺癌关系中的作用。

方法

本研究纳入了63例因盆腔肿瘤性肿块接受手术的患者,其中30例在组织病理学检查中被诊断为1至3级卵巢腺癌,33例被诊断为1至4级子宫内膜异位症。卵巢子宫内膜样腺癌患者的平均年龄为51.8±12.4岁,而卵巢透明细胞腺癌患者的平均年龄为59.5±13.7岁。卵巢癌根据1989年FIGO分级系统进行分级。子宫内膜异位症患者的平均年龄为37±11.9岁。从伊兹密尔大学医学院病理科档案中的石蜡块上获取新切片,置于经赖氨酸处理的载玻片上,并使用小鼠单克隆抗体(MMAC1,28H6克隆,英国诺沃卡斯尔公司)进行免疫组织化学染色,以检测MMAC1蛋白。细胞核上的棕色染色被视为阳性免疫反应。免疫反应性染色以整个标本上的染色百分比进行评估。

结果

在免疫组织化学研究纳入的63例患者中,18例被诊断为卵巢子宫内膜样腺癌,12例被诊断为卵巢透明细胞腺癌,33例为卵巢子宫内膜异位症。在卵巢子宫内膜样腺癌组(r = -0.41,p = 0.08)和卵巢子宫内膜异位症组(r = 0.12,p = 0.50)中,年龄与MMAC免疫染色之间未观察到显著相关性,而在卵巢透明细胞腺癌组中观察到显著相关性(r = 0.631,p = 0.02)。在卵巢子宫内膜样腺癌组(r = 0.056,p = 0.82)、卵巢子宫内膜异位症组(r = 0.21,p = 0.36)和卵巢透明细胞腺癌组(r = 0.363,p = 0.24)中,CA125水平与MMAC免疫染色之间未观察到显著相关性。子宫内膜异位症分期与MMAC免疫染色之间未观察到相关性(r = -0.17,p = 0.92)。子宫内膜瘤平均直径与MMAC免疫染色之间无相关性(r = -0.230,p = 198)。子宫内膜瘤平均直径为5.7±3.5(1 - 15.5)。MMAC免疫染色与卵巢子宫内膜样腺癌或卵巢透明细胞腺癌分期之间未检测到相关性(分别为r = -0.22,p = 0.37;r = 0.44,p = 0.14)。在子宫内膜异位症组与卵巢透明细胞腺癌组之间(p = 0.05)以及卵巢透明细胞腺癌组与卵巢子宫内膜样腺癌组之间(p = 0.27),未检测到与MMAC免疫染色相关的显著关系。在卵巢子宫内膜样腺癌组与子宫内膜异位症组之间观察到与MMAC免疫染色相关的显著关系(p = 0.001)。

结论

MMAC缺陷蛋白表达的免疫组织化学测定可被视为一种新的、简单且有用的技术,用于确定恶性转化风险增加的子宫内膜异位症患者、需要早期手术治疗的患者以及应更频繁接受随访控制的患者。

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