Is endometrial polyp formation associated with increased expression of vascular endothelial growth factor and transforming growth factor-beta1?

Objective

Endometrial polyp is a common cause of abnormal uterine bleeding, but the etiology and pathogenesis remain unclear. Vascular endothelial growth factor (VEGF) is angiogenic, related to thick walled vessels and transforming growth factor-beta1 (TGF-β1) is related to fibrotic tissue, which are characteristics of endometrial polyps. The primary objective of this study was to find out if endometrial polyp formation is associated with increased expression of VEGF or TGF-β1, or both. A secondary objective is to determine if the changes are related to steroid receptor expression.

Study design

This prospective study compared VEGF and TGF-β1 expression of endometrial polyps and adjacent endometrial tissue in 70 premenopausal women. The comparison of results was separately made for endometrium specimens obtained in the proliferative and secretory phases. The results were correlated with the steroid receptors (estrogen receptor and progesterone receptor) expression.

Results

The score of VEGF in glandular cells of endometrial polyps was significantly higher than the score in adjacent endometrium, both in the proliferative phase (P < 0.001) and the secretory phase (P = 0.03); the score of VEGF in stromal cells of endometrial polyps was significantly higher than the score in adjacent endometrium only in proliferative phase (P = 0.006). The score of TGF-β1 in glandular cells of endometrial polyps was significantly higher than the score in adjacent endometrium in proliferative phase (P = 0.02); whereas the score of TGF-β1 in stromal cells of endometrial polyps was significantly higher than the score in adjacent endometrium, both in the proliferative phase (P = 0.006) and the secretory phase (P = 0.008). There was a significant correlation between the expression of steroid receptors and VEGF and TGF-β1 (Spearman's correlation P < 0.001 and P < 0.05, respectively).

Conclusions

There was increased expression of TGF-β1 and VEGF in polyps compared to adjacent normal endometrial tissue. It suggested that these cytokines might play a role in endometrial polyp formation. In addition, there was a significant correlation between steroid receptor expression and VEGF and TGF-β1 expression.     

子宫内膜非典型增生79例临床病理特征分析

目的 分析子宫内膜非典型增生患者的临床病理特征.方法 选择2007年3月至2010年7月北京大学人民医院收治的诊断为子宫内膜非典型增生患者79例,其中49例(62%)为单纯子宫内膜非典型增生(增生组),30例(38%)为子宫内膜非典型增生合并癌变(癌变组).回顾性分析子宫内膜非典型增生患者的临床病理特征[包括年龄、孕产次、体质指数(BMI)、绝经及阴道流血情况、合并症、B超检查等],并对两组患者进行比较.分析了分段诊刮及宫腔镜检查在子宫内膜非典型增生诊断中的价值.结果 (1)年龄:患者平均年龄为(50±11)岁,其中癌变组为(51±11)岁,增生组为(50±10)岁,两组比较,差异无统计学意义(P=0.994).(2)孕产次:两组患者孕产次分别比较,差异均无统计学意义(P＞0.05).(3)合并症:增生组和癌变组有合并症的患者分别为23例(47%)和13例(43%),两组比较,差异无统计学意义(P=0.755).(4)BMI:癌变组明显高于增生组[分别为(27.9±5.4)和(25.2±2.9)kg/m2,P=0.024].(5)绝经及阴道流血情况:绝经后患者癌变组为50%(15/30),增生组为31%(15/49),两组比较,差异无统计学意义(P=0.085);绝经后阴道流血患者癌变组为13/15,增生组为8/15,两组比较,差异无统计学意义(P=0.109);未绝经有月经改变患者癌变组为12/15,增生组为68%(23/34),两组比较,差异无统计学意义(P=0.590).(6)B超检查:癌变组阳性(指官腔有回声团)率明显高于增生组[分别为73%(22/30)和51%(25/49),P=0.050].(7)分段诊刮和官腔镜检查的诊断价值:行分段诊刮活检患者23例(29%)、宫腔镜活检44例(56%),两者对非典型增生的初次诊断率分别为87%(21/23)和93%(41/44),对非典型增生伴癌变的初次诊断率分别为6/12和12/16,诊断为非典型增生的患者中癌变的漏诊率分别为6/13和19%(4/21),分别比较,差异均无统计学意义(P＞0.05).结论 对于围绝经期异常阴道流血患者,应积极进行分段诊刮及官腔镜检查,分段诊刮或官腔镜活检诊断为子宫内膜非典型增生患者中,若其BMI较高或B超提示官腔有回声团,应警惕合并子宫内膜癌的可能.

Abstract：

Objective To explore the clinicopathological characteristics in atypical endometrial hyperplasia patients. Methods A retrospective study was carry out on 79 cases with atypical endometrial hyperplasia patients admitted to Department of Gynecology, Peking University People's Hospital from Mar.2007 to Jul. 2010. All patients were divided into two groups, hyperplasia group (merely atypical endometrial hyperplasia, 49 cases, 62%) and cancerization group (atypical endometrial hyperplasia accompanying endometrial carcinoma, 30 cases, 38%). Results The mean age of 79 cases were (50 ± 11) years old ,while they were (50 ± 10) and (51 ± 11) years old for hyperplasia group and cancerization group, there were not difference (P = 0.994). The gravidity and delivery frequencies were also not differently between two groups. The rates of complicated other diseases were 47% (23/49) and 43% (13/30), which was not significantly different (P = 0.755). The body mass index (BMI) of cancerization group was higher than that of hyperplasia group [(27.9 ± 5.4) vs. (25.2 ± 2.9) kg/m2, P = 0.024]. There were 50% (15/30) and 31% (15/49) menopause cases in two groups, respectively. Among them there were 13/15 and 8/15 cases showed vaginal bleeding. Among premenopausal patients, there were 12/15 and 68% (23/34) showed abnormal vaginal bleeding, but there were not significantly different between two groups (all P ＞ 0.05). The uterine cavity mass found by ultrasonography in the cancerization group patients was more than that in hyperplasia group [73% (22/30) vs. 51% (25/49), P = 0.050]. There were 23 cases (29%), 44 cases (56%) and 12 cases (15%) were diagnosed by dilatation and curettage (D&G), hysteroscopy and hysterectomy, respectively. The rates of diagnosing atypical endometrial hyperplasia by D&G and hysteroscopy were 87 % (21/23) and 93 % (41/44), respectively. The rate of diagnosis of canceration were 6/12 and 12/16, respectively. While, the rate of missed diagnosis of canceration in the atypical endometrial hyperplasia patients by D&G and hysteroscopy were 6/13 and 19% (4/21) ,respectively. Which all did not shown significantly different (P ＞ 0.05). Conclusion Hysteroseopy or D&G should be chosen on those peri-menopausal patients with abnormal bleeding, while those atypical endometrial hyperplasia patients with high BMI and uterine cavity mass diagnosed with D&G and ultrasonography should consider the possibility of canceration.     

子宫内膜癌淋巴结转移的特征及对预后的影响

目的 探讨子宫内膜癌淋巴结转移的特征及对预后的影响.方法 回顾性分析2000年7月至2008年2月间于北京大学人民医院妇科接受手术治疗并行淋巴结切除术的227例子宫内膜癌患者的临床病理资料.结果 (1)淋巴结转移的特征:227例患者均行盆腔淋巴结切除术,22例(9.7%)有盆腔淋巴结转移;此22例患者中20例进行盆腔淋巴结分组,12例有多组盆腔淋巴结转移,最常见的淋巴结转移部位为髂外淋巴结(12/20);138例患者同时行腹主动脉旁淋巴结切除术,6例(4.4%)有腹主动脉旁淋巴结转移,其中5例合并盆腔淋巴结转移.(2)淋巴结转移的影响因素分析:不同年龄、宫颈和附件受累情况、肌层浸润深度、病理分级、ER表达的患者间盆腔淋巴结转移率比较,差异均有统计学意义(P＜0.05);而不同病理类型和PR表达的患者间盆腔淋巴结转移率比较,差异均无统计学意义(P＞0.05).上述不同因素的患者间腹主动脉旁淋巴结转移率比较,差异均无统计学意义(P＞0.05).(3)淋巴结转移患者的预后:有、无盆腔淋巴结转移患者的3年无瘤生存率分别为(81.8±8.2)%和(97.4 4±1.2)%,两者比较,差异有统计学意义(P=0.004);有、无腹主动脉旁淋巴结转移患者的3年无瘤生存率分别为100%和(96.7 4±1.6)%,两者比较,差异无统计学意义(P＞0.05).(4)子宫内膜癌患者复发的影响因素分析:单因素分析显示,患者年龄＞50岁、附件受累、盆腔淋巴结转移患者的复发率明显升高(P＜0.01);而宫颈受累、肌层浸润深度、腹主动脉旁淋巴结转移、病理类型、病理分级情况与复发无关(P＞0.05).Cox回归法分析显示,附件受累和患者年龄是影响患者复发的独立危险因素(P=0.011,P=0.025).结论 子宫内膜癌盆腔淋巴结转移最常见于髂外淋巴结,腹主动脉旁淋巴结转移常合并有盆腔淋巴结转移.宫颈、附件受累及深肌层浸润、病理分级高、ER阴性的患者较易发生盆腔淋巴结转移,有盆腔淋巴结转移患者的预后较差.

Abstract：

Objective To explore the lymph nodes (LN) metastasis characters of the endometrial carcinoma and its relation with the patients' prognosis. Methods A retrospective study was carried out on 227 cases of endometrial carcinoma who admitted to our department and underwent LN excision from Jul. 2000 to Feb. 2008. Results Among 227 cases who underwent pelvic LN excision, there were 22 cases (9.7%) presented LN metastasis. There were 12 cases with positive external iliac LN from 20 cases of patients with data in LN grouping. Para-aortic LN excision was carried out on 138 patients. There were 6 cases with positive para-aortic LN, 5 cases of them together with pelvic LN metastasis. Those patients with cervix involvement, annex metastasis, deep myometrium infiltration, grade 2-3 and negative estrogen receptor occurred pelvic LN metastasis more frequently than the others ( P ＜ 0. 05 ). Among the 6 cases with positive para-aortic LN, there were 3 cases ( 3/6) with deep myometrium infiltration. For those whose paraaortic LN was negative, it was only 16. 7% (22 cases). But there were no difference statistically between them ( P＞ 0. 05 ). There were significant difference in 3 years disease-free survival rate between patients with positive pelvic LN or negative pelvic LN [(81. 8 ± 8. 2)% vs ( 97. 4 ± 1. 2 ) % , P = 0. 004]. While there were not significant difference in 3 years disease-free survival rate between patients with positive para-aortic LN or negative para-aortic LN [100% vs ( 96. 7 ± 1. 6) % , P ＞ 0. 05]. Single factor analysis showed that the age more than 50 years, annex metastasis and pelvic LN metastasis related with the recurrence (P ＜0. 01). But cervix involvement, deep myometrium infiltration, para-aortic LN metastasis, pathology type, tumor grade and estrogen receptor did not relate with the recurrence ( P ＞ 0. 05 ). Cox regression analysis showed that annex metastasis and the age of patients were independent risk factors affecting the recurrence ( P = 0. 011, P = 0. 025 ). Conclusions The most common site of pelvic LN metastasis is the external iliac LN for endometrial carcinoma patients. The patients with positive para-aortic LN always accompanied pelvic LN metastasis. Those patients with cervical involvement, annex metastasis, deep myometrium infiltration, poor differentiation and negative estrogen receptor be more likely exist pelvic LN metastasis. Pelvic LN metastasis may affect the prognosis of endometrial carcinoma patients.     

子宫内膜癌抑癌基因研究进展

子宫内膜癌是妇女常见的恶性肿瘤之一,发病率有逐年上升的趋势。随着分子生物学和免疫学的发展,关于子宫内膜癌分子水平的致癌机制研究日益深入,如癌基因、抑癌基因、DNA错配修复基因、雌激素代谢酶相关基因、甾体激素受体基因和细胞周期调控蛋白等。综述目前研究热点——抑癌基因的进展,为进一步探讨子宫内膜癌的发生发展、临床治疗及预后的判断提供重要依据。     

不孕症患者临床情况与子宫内膜息肉的关系研究

目的:探讨不孕症患者临床情况和子宫内膜息肉的关系,为临床诊治提供参考。方法:收集2008年11月至2009年10月间于本院行宫腹腔镜联合检查的244例不孕患者的临床资料,分别进行年龄、不孕年限、腹腔镜检查盆腔疾病和孕产史等与子宫内膜息肉发生的关系分析。同时分析B超检查与宫腔镜检查子宫内膜息肉的一致性。结果:不孕患者年龄、盆腔炎症情况在不同组别间子宫内膜息肉发生率差异无统计学意义(P均>0.05)。而不孕年限、孕产史以及子宫内膜异位症和子宫内膜息肉发生有关。随不孕年限增加,子宫内膜息肉发生率呈增高趋势(P=0.034),原发不孕组比继发不孕组子宫内膜息肉发生率高(15.71%vs5.8%,P=0.016),子宫内膜异位症组比无子宫内膜异位症组的子宫内膜息肉发生率高(19.0%vs7.5%,P=0.007)。宫腔镜检查子宫内膜息肉阳性率高于B超检查(11.5%与6.6%,P=0.000)。结论:子宫内膜息肉发生与不孕症患者不孕年限、病因、孕产史等因素相关,B超结合宫腔镜检查是排除内膜息肉有效手段。     

年轻子宫内膜癌患者保留卵巢的风险评估

目的:探讨年轻子宫内膜癌患者合并卵巢恶性病变的高危因素,从而对年轻早期内膜癌患者保留卵巢的安全性进行评估。方法:回顾2005年11月～2009年12月在我院行手术治疗的238例≤45岁子宫内膜癌患者的临床病理资料,分析子宫内膜癌患者发生卵巢恶性病变的高危因素,并随访了37例保留单侧或双侧附件的患者。结果:13例(5.5%)患者合并卵巢恶性肿瘤,其中8例(3.4%)为子宫内膜癌卵巢转移,5例(2.1%)为原发双癌。多因素分析子宫内膜癌卵巢转移的危险因素,按危险强度排列为组织学类型、宫颈受累、血清CA125水平及卵巢包块大小;而原发双癌的危险因素仅为卵巢包块大小。对37例保留单侧或双侧附件的患者进行定期随访,平均随访时间28.7±12.4个月(6～57个月),期间未发现复发病例。结论:5.5%的子宫内膜癌患者合并卵巢恶性肿瘤,保留其卵巢具有很大风险,对有强烈愿望保留卵巢的年轻患者必须进行充分的术前及术中评估,全面的医患沟通及术后随访亦必不可少。