MDM2在卵巢浆液性和黏液性上皮肿瘤中的表达

Abdelaal Shereen E, Habib Fahima M, El Din Amina A Gamal, Gabal Samia M, Hassan Nabila S, Ibrahim Nihad A

Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt Email :

Asian Pac J Cancer Prev. 2016;17(7):3295-300.

BACKGROUND

Different types of cancer exhibit abnormalities in cell cycle regulators. The murine double minute2(MDM2) cell cycle regulator is a protooncogene that negatively regulates the P53 tumour suppressor gene. Surface epithelial tumours constitute approximately two thirds of ovarian neoplasms. Each histologic type can be classified as benign, borderline and malignant. This study aimed to examine immunohistochemical expression of the MDM2 protein in ovarian serous and mucinous epithelial tumours (benign, borderline and malignant).

MATERIALS AND METHODS

This study included forty five ovarian tumours, subdivided into fifteen cystadenomas (5 serous and 10 mucinous), fifteen borderline tumours (11 serous and 4 mucinous) and fifteen cystadenocarcinomas (9 serous and 6 mucinous). Paraffin sections were stained with haematoxylin and eosin for histopathologic study, and with mouse monoclonal antiMDM2 antibody for immunohistochemistry.

RESULTS

MDM2 positivity was detected in 28.9% of the studied ovarian tumours. All benign tumours were negative and positivity was significantly higher in malignant than borderline tumours (P value of chisquare test =0.000). Significantly, all MDM2 positive mucinous tumours were malignant with no positive mucinous borderline tumours. Malignant tumours showed positive MDM2 expression in 83.3% of mucinous type and in 55.6% of serous type. Borderline serous tumours showed negative MDM2 in 72.7% of cases (P value of Z test =0.04).

CONCLUSIONS

Alterations in the expression of the cell cycle regulator (MDM2) occur early in the process of tumourigenesis in serous and mucinous ovarian tumours. We suggest that MDM2 may be used in those tumours as a marker for risk stratification and identification of cases with cancer development and progression. We recommend further studies on MDM2 immunohistochemistry, in conjunction with adjuvant methods as DNA ploidy and FISH gene amplification, focusing on the mucinous tumours and differentiating between the three tumour categories, benign, borderline and malignant.

背景

不同类型的癌症在细胞周期调节因子方面表现出异常。小鼠双微体2（MDM2）细胞周期调节因子是一种原癌基因，对P53肿瘤抑制基因起负调节作用。表面上皮性肿瘤约占卵巢肿瘤的三分之二。每种组织学类型可分为良性、交界性和恶性。本研究旨在检测MDM2蛋白在卵巢浆液性和黏液性上皮性肿瘤（良性、交界性和恶性）中的免疫组化表达。

材料与方法

本研究包括45例卵巢肿瘤，分为15例囊腺瘤（5例浆液性和10例黏液性）、15例交界性肿瘤（11例浆液性和4例黏液性）和15例囊腺癌（9例浆液性和6例黏液性）。石蜡切片用苏木精和伊红染色进行组织病理学研究，并用小鼠单克隆抗MDM2抗体进行免疫组化。

结果

在所研究的卵巢肿瘤中，28.9%检测到MDM2阳性。所有良性肿瘤均为阴性，恶性肿瘤中的阳性率显著高于交界性肿瘤（卡方检验P值=0.000）。值得注意的是，所有MDM2阳性的黏液性肿瘤均为恶性，无阳性的黏液性交界性肿瘤。恶性肿瘤中，黏液性类型的MDM2阳性表达率为83.3%，浆液性类型为55.6%。交界性浆液性肿瘤72.7%的病例MDM2呈阴性（Z检验P值=0.04）。

结论

细胞周期调节因子（MDM2）表达的改变在卵巢浆液性和黏液性肿瘤的肿瘤发生过程中早期出现。我们建议MDM2可用于这些肿瘤的风险分层以及识别癌症发生和进展的病例。我们建议进一步开展MDM2免疫组化研究，并结合DNA倍体和FISH基因扩增等辅助方法，重点研究黏液性肿瘤，并区分良性、交界性和恶性这三种肿瘤类型。