探讨子宫内膜癌(EC)肿瘤组织中血管生成拟态(VM)、基质金属蛋白酶(MMP)-2的表达及其与EC的临床关系。

选择2010年10月至2013年12月，济南军区总医院妇产科具有完整临床病历资料，并行手术切除子宫的52例EC患者(EC组)，21例同期在本院因子宫肌瘤等良性疾病行子宫切除术患者(正常组)，以及12例术后病理检查结果诊断为子宫内膜不典型增生(EIN)患者(EIN组)的子宫内膜石蜡包埋切片为研究对象。对石蜡包埋切片采用CD₃₄及过碘酸雪夫(PAS)双重染色法，观察VM在上述3组的表达情况，同时对EC组石蜡包埋切片进行免疫组化SP染色，观察MMP-2表达情况。统计学分析EC组52例患者不同临床因素[年龄，国际妇产科联盟(FIGO)临床分期，世界卫生组织(WHO)病理分级，肌层浸润深度及有无淋巴结转移]间VM阳性表达率及MMP-2高表达率差异，以及EC组中VM与MMP-2表达的相关性。本研究遵循的程序符合济南军区总医院人体试验委员会制定的伦理学标准，得到该委员会批准，征得受试对象知情同意，并与之签署临床研究知情同意书。3组患者年龄、是否绝经、生育史、月经史等一般临床资料比较，差异无统计学意义(P>0.05)。

①EC组患者肿瘤组织VM阳性表达率为30.8%(16/52)，而在正常组及EIN组受试者的子宫内膜中均未发现VM形成。②FIGO临床分期为Ⅰ期患者VM阳性表达率较Ⅲ～Ⅳ期低(14.3%vs 70.0%)，且差异有统计学意义(P＝0.002)；WHO病理分级为高、中、低分化的EC患者之间两两比较，分化级别高者较分化级别低者VM阳性表达率低，且差异均有统计学意义(P<0.05)；有淋巴结转移患者VM阳性表达率较无淋巴结转移患者高(66.7%vs 23.3%)，且差异有统计学意义(χ²＝4.704，P＝0.030)；VM阳性表达率在≤50岁和>50岁患者之间，以及肌层浸润深度<1/2肌层和≥1/2肌层患者之间比较，差异均无统计学意义(P>0.05)。③有淋巴结转移患者MMP-2高表达率较无淋巴结转患者高(88.9%vs 23.2%)，且差异有统计学意义(χ²＝11.413，P＝0.000)；MMP-2高表达率在≤50岁和>50岁患者之间，FIGO临床分期为Ⅰ期、Ⅱ期和Ⅲ～Ⅳ期患者之间，WHO病理分级为高、中、低分化的EC患者之间，以及肌层浸润深度<1/2肌层和≥1/2肌层患者之间比较，差异均无统计学意义(P>0.05)。④EC组52例患者肿瘤组织中，VM形成与MMP-2表达存在正相关关系(r＝0.478，P＝0.000)。

部分EC患者肿瘤组织中存在VM，并可能与EC病情严重程度有关。MMP-2可能促进VM形成，二者共同作用可能促进EC的淋巴结转移。

To study the expression of vasculogenic mimicry (VM) and matrix metalloproteinase(MMP)-2 in endometrial carcinoma (EC) tumor tissue and their clinical relationship with EC.

A total of 52 EC patients at the Jinan Military General Hospital from October 2010 to December 2013 were selected as EC group, which underwent hysterectomy and had complete clinical data. Another 21 cases over the same period as control group, which had hysterectomy because of the uterine fibroids or other benign diseases. Furthermore, 12 cases of pathological findings diagnosed as atypical endometrial hyperplasia(EIN) patients were selected as EIN group. Endometrial paraffin-embedded sections of all patients were taken for the study. All of the paraffin-embedded sections adopted staining of CD₃₄ and periodic acid-schiff (PAS) together, and observed the expression of VM in three groups, while the paraffin-embedded sections of EC group were stained by immunohistochemistry streptavidin-perosidase (SP) in order to observe the expression of MMP-2. The differences of the positive expression rates of VM and the high expression rates of MMP-2 in different clinical factors among 52 cases of EC patients, including age, International Federation of Gynecology and Obstetrics(FIGO) clinical stages, World Health Organization(WHO) pathological differentiated grading, the infiltrating depth of muscular layer and whether had lymph node metastasis, were statistically analyzed. Meanwhile, the correlation between the expression of VM and MMP-2 in EC group were analyzed. This study followed the Ethical Standards of the Human Trials Committee of the Jinan Military General Hospital, had the approval of the commission. Informed consent was obtained from each participant. There were no significant differences among three groups in general clinical data, such as the age, menopause, childbearing history, menstrual history, etc.(P>0.05).

①The positive rate of VM in the tumor tissue of EC group was 30.8%(16/52), but did not find VM express in endometrium in control group and EIN group. ②The positive expression rate of VM in stageⅠpatients of FIGO was lower than that of stage Ⅲ-Ⅳ(14.3%vs 70.0%), and the difference was statistically significant(P=0.002); WHO pathological differentiated grading between well, moderately and poorly differentiation of the EC patients had pairwise comparisons, showed the higher level of differentiation had a lower VM positive expression rate than the lower level of differentiation, and the differences were statistically significant(P<0.05); The VM positive expression rate in patients with lymph node metastasis was higher than that in patients without lymph node metastasis(66.7%vs 23.3%), and the difference was statistically significant(χ²=4.704, P=0.030); There were no significant differences of VM positive expression rate between ≤50 years and >50 years old patients, between patients with infiltrating depth of muscular layer <1/2 and ≥1/2(P>0.05). ③The high expression rate of MMP-2 in patients with lymph node metastasis was higher than that in patients without lymph node metastasis(88.9%vs 23.2%), and the difference was statistically significant(χ²=11.413, P=0.000); There were no significant differences of high expression rate of MMP-2 between patients ≤50 years and >50 years old, among FIGO clinical stageⅠ, Ⅱ and Ⅲ-Ⅳ, among WHO pathological differentiated grading of well, moderately and poorly, between the infiltrating depth of muscular layer <1/2 and ≥1/2(P>0.05). ④The correlation of expression level of VM and MMP-2 were positively correlated in the 52 cases tumor tissue in EC group(r=0.478, P=0.000).

VM exists in some EC tissues and was related to the severity of EC. MMP-2 may promotes the formation of VM. Both of VM and MMP-2 may together promote the lymph node metastasis of EC patients.