Heparanase expression in both normal endometrium and endometrial cancer

The aim of this study was to investigate the relationship between heparanase expression and prognostic factors in endometrial cancer, as well as the relationship between heparanase expression during phases of the normal endometrial cycle. Immunohistochemical analysis of 166 endometrial cancers and 34 normal endometria in various phases of growth was performed. The heparanase expression in the late-proliferative phase of normal endometria was found to be significantly higher than in either the early-proliferative or the secretory phases (P= .012 and P= .044, respectively). Heparanase expression was also significantly higher in endometrial cancer patients with tumors of an advanced FIGO stage (P= .0003) and high FIGO grade (P= .004) and with cancers showing either deep myometrial invasion (P= .023), lymph node metastasis (P= .006), lymphvascular space involvement (P= .048), or positive peritoneal cytology (P= .010). The disease-free and overall survival rates of patients with intense heparanase expression were significantly lower than those of patients with absent or moderate heparanase expression (P= .004 and P= .002, respectively). Heparanase may participate in normal endometrial remodeling and can serve as an indicator of the aggressive potential and poor prognosis of endometrial cancers.     

Occult lymph node metastases detected by cytokeratin immunohistochemistry predict recurrence in node-negative endometrial cancer

OBJECTIVE: Even after curative resection of early endometrial cancer, some patients die as a result of recurrence. We believe that these patients likely had occult lymph node metastases at the time of diagnosis. In an attempt to identify the responsible occult metastases, the clinicopathological significance of cytokeratin expression in lymph nodes with unconfirmed metastasis was evaluated retrospectively in patients with endometrial carcinoma. METHODS: We examined 304 pelvic lymph nodes and 46 primary tumors excised from 46 patients with endometrial cancer, including 36 with Stage I disease and 10 with Stage IIIc disease. Formalin-fixed paraffin-embedded tissue sections were stained immunohistochemically using antibodies against cytokeratin, CA125, and macrophage-related antigen. Sections were also stained with hematoxylin and eosin. RESULTS: In 10 patients with Stage IIIc disease, cytokeratin expression was detected in cells other than the tumor cells in all 13 lymph nodes with metastasis and also in 20 (30.3%) of 66 lymph nodes without metastasis. Cytokeratin expression was observed in 37 (16.4%) of 225 lymph nodes with unconfirmed metastasis, which were obtained from 14 of 36 patients with Stage I disease. Five of fourteen patients with lymph nodes expressing cytokeratin had recurrent disease in the pelvic cavity, while all 22 patients with unconfirmed cytokeratin expression in their lymph nodes showed no recurrence. Cytokeratin and CA125 were detected simultaneously on macrophages in lymph nodes. Cytokeratin expression in lymph nodes was closely related to lymph-vascular space involvement of the primary tumor, but was not related to either histological grade or depth of myometrial invasion. Multivariate analysis identified cytokeratin expression as an independent risk factor for recurrence in Stage I endometrial cancer. CONCLUSIONS: The immunohistochemical expression of cytokeratin in lymph nodes with undetected metastases predicts occult metastasis to these nodes and is a risk factor for recurrence in early-stage endometrial cancer.     

细胞角蛋白在子宫内膜癌淋巴结中的表达及意义

目的 :研究细胞角蛋白 (cytokeratin ,CK)在子宫内膜癌淋巴结中的表达及其意义。方法 :采用免疫组化SP法检测 5 0例子宫内膜癌患者的淋巴结 2 98枚中CK的表达。结果 :(1)在转移淋巴结中 ,CK皆呈强阳性表达 ,其阳性表达率为 10 0 %。在Ⅰ、Ⅱ、Ⅲc期无转移淋巴结中 ,CK皆呈弱阳性表达 ,其阳性表达率分别为 14 .5 %、15 .1%和 16 .4 % ,3期差异无显著性 (P >0 .0 5 ) ;(2 )Ⅰ、Ⅱ期病例的淋巴结中CK表达在肌层浸润深度、组织学类型、组织学分级 3组的组内差异无显著性 (P >0 .0 5 ) ;而淋巴管浸润组的组内差异有显著性 (P <0 .0 5 ) ;(3)Ⅰ、Ⅱ期病例的淋巴结中CK表达及其他预后因素与肿瘤复发的关系 ,淋巴结中CK表达、淋巴管浸润、术后治疗 3组的组内差异有显著性 (P <0 .0 5 ) ,而肌层浸润深度、组织学类型、组织学分级 3组的组内差异无显著性 (P >0 .0 5 ) ;(4 )对子宫内膜癌的诸预后因素如肌层浸润深度、组织学类型、组织学分级、淋巴结中CK表达、淋巴管浸润、术后治疗等进行多元回归分析 ,结果显示 :淋巴结中CK表达是Ⅰ、Ⅱ期子宫内膜癌患者复发的唯一相关因素。结论 :在无转移淋巴结中 ,CK表达与淋巴管浸润有关 ,提示可能存在淋巴结微转移 ,是Ⅰ、Ⅱ期子宫内膜癌复发的独立危险因素     

Angiogenesis-prognostic factor in patients with endometrial cancer

Endometrial carcinoma is one of the most commonly found cancers. In numerous kinds of cancers, tumor microvessel density correlates with clinical stage of disease and is considered as an independent prognostic factor. Evaluation of angiogenesis intensity in endometrial cancer also seems to be an independent prognostic factor and statistically correlates with FIGO stage of disease, histological type and grade of tumor, depth of myometrial invasion and metastasis. Activity of angiogenic factors in human tissues and serum provides additional reference concerning the growth and progression of endometrial cancer.     

Lymph-vascular space invasion and number of positive para-aortic node groups predict survival in node-positive patients with endometrial cancer

OBJECTIVE: The aim of this study was to determine pathologic variables associated with disease-specific survival of node-positive patients with endometrial carcinoma treated with combination of surgery including pelvic and para-aortic lymphadenectomy and adjuvant chemotherapy. METHODS: Survival of 55 node-positive endometrial carcinoma patients prospectively treated with surgery and adjuvant chemotherapy between 1982 and 2002 at Hokkaido University Hospital was compared to various histopathologic variables. All patients underwent primary surgical treatment including pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy consisting of intravenous cisplatin, doxorubicin, and cyclophosphamide. Survival analyses were performed by the Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis using a forward stepwise selection. RESULTS: Among 303 consecutive endometrial cancer patients treated during the period of this study, 55 patients (18.2%), including 44 without peritoneal metastasis (FIGO stage IIIc) and 11 with peritoneal metastasis (FIGO stage IV), were found to have retroperitoneal lymph node metastasis. Multivariate Cox regression analysis revealed that peritoneal metastasis and lymph-vascular space invasion (LVSI) were independently related to poor survival in node-positive endometrial carcinoma. The estimated 5-year survival rate of stage IIIc patients with or without moderate/prominent LVSI was 50.9% and 93.3%, respectively with statistically significant difference (P=0.0024). The estimated 5-year survival rate of stage IV patients was 20.0%. Prognosis of stage IIIc patients could be stratified into three groups by the number of positive para-aortic node (PAN) with an estimated 5-year survival rate of 86.4% for no positive PAN (n = 23), 60.4% for one positive PAN (n = 13), and 20.0% for > or = 2 positive PAN (n = 8). The difference of survival rate between no or one positive PAN and > or = 2 positive PAN was statistically significant (P = 0.0007 for no positive PAN vs > or = 2 positive PAN, P = 0.0319 for one positive PAN vs > or = 2 positive PAN). Multivariate analysis including number of positive PAN groups showed that LVSI, number of positive PAN groups were independent prognostic factors for survival. Survival of patients with stage IIIc disease could be stratified into three groups by combination of LVSI and number of positive PAN groups with an estimated 5-year survival rate of 93.3% for no or one positive PAN group with nil or minimal LVSI, 62.6% for no or one positive PAN group with intermediate or prominent LVSI, and 20.0% for > or = 2 positive PAN groups irrespective of LVSI (P = 0.0002 for no or one positive PAN group with nil or minimal LVSI vs > or = 2 positive PAN groups, P = 0.0223 for no or one positive PAN group with nil or minimal LVSI vs no or one positive PAN group with intermediate or prominent LVSI, P = 0.0388 for no or one positive PAN group with intermediate or prominent LVSI vs > or = 2 positive PAN groups). CONCLUSIONS: LVSI and number of positive PAN groups were independent prognostic factors for stage IIIc endometrial cancer patients. Postoperative therapy and follow-up modality need to be individualized according to LVSI and the number of positive PAN for stage IIIc patients. New molecular markers to predict the prognosis of endometrial cancer patients preoperatively should be found for individualization of treatment. New chemotherapy regimen including taxane needs to be considered as an adjuvant therapy for patients with node-positive endometrial cancer.     

Angiogenesis in endometrial carcinoma: correlation with survival and clinicopathologic risk factors

Association among angiogenesis, survival and clinicopathologic parameters in endometrial carcinoma was evaluated. Sixty patients who had been diagnosed as endometrial carcinoma, from 1993 to 1998, were included in the study. All patients had been surgically staged with bilateral pelvic and para-aortic lymph node dissection. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. The area with the most intensified microvasculature was determined under low-power (x100) magnification, and the microvessel count of this area under high-power (x200) magnification was determined as the microvessel density (MVD) of the tumor. The mean MVD was 26.2 +/- 13.0 (range 6-68), and it was considered as high (n = 24; 40%), moderate (n = 19; 31.7%) and low (n = 17; 28.3%) when the MVD was >30, between 15-30 and <15, respectively. Statistical analysis included Mann-Whitney, Kruskal-Wallis and Spearman rank correlation tests. The Kaplan-Meier method was used to evaluate the difference between angiogenesis and survival. Multivariate analysis with the Cox regression model was used in MVD values and different clinicopathological parameters. There was positive correlation between MVD increase and surgicopathological stage (p < 0.05). A significant difference was seen between MVD increase and lymph node metastasis (p < 0.05). There were no differences between MVD and age, histological type, grade and lymphovascular invasion. MVD did not change in association with myometrial invasion depth. There was a significant difference in means of survival between the low and high MVD groups (p = 0.01). However, MVD was not an independent prognostic factor in multivariate analysis. Increased angiogenesis was found to be associated with advanced stage and decreased survival in endometrial carcinoma.     

子宫内膜癌卵巢转移危险因素的探讨

目的 探讨子宫内膜癌卵巢转移的危险因素及手术中保留卵巢的可行性.方法 回顾性分析1997年1月至2006年12月在江西省妇幼保健院首治为手术治疗的638例子宫内膜癌患者的临床病理资料.结果 36例(5.6%,36/638)患者发生卵巢转移.单因素分析显示,子宫内膜癌卵巢转移的相关因素为病理类型、病理分级、子宫肌层浸润、腹水或腹腔冲洗液细胞学检查阳性、盆腔淋巴结转移、宫旁浸润、腹主动脉旁淋巴结转移、子宫浆膜浸润(P均＜0.05),而年龄、脉管浸润、宫颈浸润与卵巢转移无明显相关性(P均＞0.05).多因素分析显示,子宫内膜癌卵巢转移的独立危险因素按危险强度排列为:盆腔淋巴结转移、腹水或腹腔冲洗液细胞学检查阳性、病理分级.结论 子宫内膜样腺癌、细胞高分化、无盆腔淋巴结转移、无腹主动脉旁淋巴结转移、元肌层浸润、腹水或腹腔冲洗液细胞学检查阴性、年轻的患者可考虑手术中保留卵巢.     

Prognostic significance of DNA topoisomerase II-alpha (Ki-S1) immunoexpression in endometrial carcinoma

OBJECTIVE: In order to determine the significance of proliferative activity (PA) in endometrial carcinomas, we analysed the expression of cell cycle-related antigens in routinely processed tissue. MATERIALS AND METHODS: Serial sections of 113 endometrial carcinoma specimens were immunostained with the monoclonal antibody DNA Topoisomerase II-alpha (Ki-S1). In addition to Topoisomerase II-alpha (Ki-S1) staining, histologic type, International Federation of Gynecology and Obstetrics (FIGO) stage. FIMO grade, depth of myometrial invasion, tumor size, lymphovascular space invasion, serosal and/or adnexal involvement, lymph node metastasis, age and peritoneal cytology were evaluated as prognostic indicators. The median follow-up time was 23 (range, 1 to 126 ) months. RESULTS: FIGO stage, FIGO grade, tumor size, lymphovascular space invasion, lymph node metastasis, peritoneal cytology and Topoisomerase II-alpha (Ki-S1) expression all significantly influenced survival in univariate analyses (p < or = 0.05). In the Cox regression analysis, Topoisomerase II-alpha (Ki-S1), serosal and/or adnexal involvement, and lymph node metastasis expression were the only variables with independent prognostic impact (p < or = 0.05), whereas FIGO stage, FIGO grade, histologic type FIGO grade, depth of invasion, tumor size, lymphovascular space invasion, age and peritoneal cytology had no independent influence (p > 0.05). Topoisomerase II-alpha (Ki-S1) staining was significantly elevated in advanced (Stage II, III, IV) as opposed to early (Stage I) carcinomas (p < or = 0.05). CONCLUSION: The association with established prognosticators for endometrial carcinomas, and the results of uni- and multivariate analysis indicate that the additional evaluation of DNA Topoisomerase II-alpha (Ki-S1) peptide antibody (PA) is useful for classifying patients into subgroups with low and high risk of relapse which might help to individualize the therapeutic strategy in endometrial carcinomas.     

Intratumor flowmetry in endometrial carcinoma. Correlation with the tumor stage

BACKGROUND: To assess the value of intra-tumoral (endometrial) flow as detected by color Doppler ultrasound in relationship with negative prognostic factors in patients with endometrial carcinoma. METHODS: Fifty-three patients with a previous histological diagnosis of endometrial carcinoma were included in the study. Transvaginal ultrasound with pulsed color Doppler was performed in order to record resistance indexes and vascular density (defined as "high" if > or = 3 vascular spaces were detectable for any given area). All cases were classified according to FIGO after surgery and histology. Prognostic bad factors were considered: FIGO stage (> I), tumor grade (> 1), myometrial invasion (> 50%) involvement of vascular spaces and lymph node metastasis. RESULTS: Both resistance indexes and vascular density in the endometrium related well to more prognostic signs. No relationship was found for lymph node metastasis, probably justified by the small number of positive nodes (2/27). DISCUSSION: Color Doppler ultrasound seems to be a promising technique in pre-surgical staging of endometrial carcinoma. Detection of vascular spaces rather than low resistance indexes is, in personal experience, more significantly related to advanced disease. It is hypothesized that long term follow-up of these patients can show a predictive value of Doppler ultrasound on the outcome of the disease.     

Microvessel density (MVD) as a prognosticator in endometrial carcinoma

PURPOSE: To assess microvessel density (MVD) as a marker for angiogenesis in endometrial carcinoma (EC) and normal endometrium at the proliferative and secretory phase, and to determine its prognostic value on survival among cases with EC. METHODS: Forty-three endometrial carcinoma cases were surgically staged and recruited for this case-control study. Tissue specimens from hysterectomies due to benign conditions (uterine descensus, myoma uteri, chronic pelvic pain, adenomyosis), that belonged to proliferative (n = 10) and secretory (n = 10) endometrium (n = 10), were studied as the control group (n = 20). MVD was assessed in hot areas where a high density of microvessels were detected within tumoral tissue and normal endometrium at proliferative and secretory phases. Among EC, various prognosticators such as tumor stage, histological and nuclear grade, tumor size, lympho-vascular space involvement (LVSI), cervical involvement, myometrial invasion, adnexal and lymph node involvement, peritoneal cytology and MVD were analysed in regard to survival. RESULTS: The mean age of cases with EC was 58.3 +/- 1.4. MVD was apparently high in EC cases (p < 0.05). Among control cases, endometrium from proliferative and secretory phases of the menstrual cycle was not statistically different (48.5 +/- 3.6 vs 47.4 +/- 3.8, respectively). MVD was correlated with high surgical stage (p < 0.001), cervical involvement (p = 0.01), adnexal involvement (p = 0.04), lympho-vascular space involvement (p = 0.02), pelvic and para-aortic lymph node metastasis (p < 0.001) and positive peritoneal cytology (p < 0.001). On univariate analysis, with a MVD cut-off value of 81/0.739 mm2, surgical stage (p < 0.001), LVSI (p < 0.001), retroperitoneal lymph node involvement (p < 0.001), adnexal metastasis (p < 0.001), peritoneal cytology (p = 0.005) and MVD count (p < 0.001) appeared to be independent factors for survival. On multivariate analysis, only pelvic lymph node involvement (p = 0.03) and MVD (p = 0.02) were found to be independent prognosticators on survival. CONCLUSIONS: Angiogenesis is apparent in both initial and further evolution of a tumoral process. MVD appears to have a substantial prognostic value on survival in EC cases.     

子宫内膜癌雄激素受体表达及临床意义

目的:探讨子宫内膜癌组织中的雄激素受体(AR)的表达及其与临床病理特征和雌激素受体(ER)、孕激素受体(PR)表达的关系。方法:应用免疫组织化学SP法检测41例正常子宫内膜、18例不典型增生及116例子宫内膜癌组织中AR、ER、PR的表达。结果:①子宫内膜细胞普遍存在AR的表达,在正常子宫内膜、不典型增生子宫内膜、子宫内膜癌组织中阳性表达率逐渐增高,但差异无统计学意义(P=0.424)。②AR在子宫内膜癌中的表达随患者FIGO分期、组织病理分级的升高而下降(P=0.011;P=0.047),而与患者发病年龄、是否绝经、组织学类型、淋巴结有无转移、肌层有无浸润无明显关系(P>0.05)。③AR的表达与ER、PR的表达呈正相关(r=0.293,P=0.001;r=0.275,P=0.003)。结论:AR在子宫内膜癌的发生、发展中可能起重要作用,AR阳性表达者的生物学行为较好。     

The clinical significance of tumor-associated antigen RCAS1 expression in the normal, hyperplastic, and malignant uterine endometrium

OBJECTIVE: A tumor-associated antigen, RCAS1, is recognized by 22-1-1 monoclonal antibody. It was found in carcinomas derived from the uterus and ovary and was especially strongly expressed in invasive cancers. A previous investigation showed the RCAS1 expression to be correlated with a poor prognosis in uterine cervical adenocarcinoma. In this study, we examined whether the expression of RCAS1 is associated with the progression of the uterine endometrial neoplasms. METHODS: The expression of RCAS1 was evaluated by an immunohistochemical analysis. The tissue specimens used in this study included 46 cases of normal uterine endometrium, 40 cases of hyperplasia, and 121 cases of adenocarcinoma. The relationship between RCAS1 expression and several clinicopathological variables (clinical stage, histology, grade, myometrial invasion, lymph-vascular space invasion, and lymph node metastasis) was also assessed in endometrial adenocarcinoma. RESULTS: RCAS1 was positive in 26% of the normal uterine endometrium specimens (12 of 46 total cases), in 32% of the hyperplasia specimens (13 of 40 total cases), and in 68% of the adenocarcinoma specimens (83 of 121 total cases). As a result, the expression of RCAS1 was statistically higher in adenocarcinoma than in the normal and hyperplastic endometrium (P < 0.0001). RCAS1 was statistically detected more frequently in grade 3 than in grade 1 or 2 (P < 0.05); however, there was no correlation between the antigen expression and the clinical stage, myometrial invasion, lymph-vascular space invasion, or lymph node metastasis. CONCLUSION: RCAS1 expression might thus be associated with the malignant transformation and poor differentiation observed in uterine endometrial adenocarcinoma.     

不同级别卵巢浆液性癌中E-cadherin和p120蛋白的表达及意义

目的:探讨上皮性钙黏附蛋白(E-cadherin)和连环蛋白p120在不同组织学级别卵巢浆液性癌中的表达及意义。方法:用免疫组化EnVision二步法,分别检测31例卵巢低级别浆液性癌和70例卵巢高级别浆液性癌中E-cadherin和p120蛋白的表达水平,分析其与卵巢浆液性癌临床病理资料的相关性。结果:E-cadherin在低级别浆液性癌和高级别浆液性癌中的阳性率分别为71.0%和61.4%(P=0.356);p120的阳性率分别为83.9%和60.0%(P=0.018)。高级别浆液性癌中,E-cadherin和p120蛋白表达率随着FIGO分期(P=0.015和P=0.011)、淋巴结转移(P=0.001和P=0.001)及大网膜受累(P=0.028和P=0.018)显著降低。E-cadherin蛋白表达率随年龄增高显著降低(P=0.011),而p120蛋白表达率与年龄无显著相关性(P=0.226)。低级别浆液性癌中,仅p120蛋白表达率与淋巴结转移(P=0.042)、大网膜受累(P=0.048)及术前CA125水平(P=0.042)具有显著相关性。结论:卵巢高级别浆液性癌中p120蛋白的表达缺失率显著高于卵巢低级别浆液性癌,同时仅在高级别浆液性癌中E-cadherin和p120的低表达均与FIGO分期和肿瘤转移潜能相关,提示E-cadherin和p120蛋白可能在不同级别卵巢浆液性癌的发生发展中具有不同的作用。     

Prognostic significance of epithelial-stromal vascular cuffing and microvessel density in squamous cell carcinoma of the uterine cervix.

OBJECTIVE: Tumor angiogenesis has been shown to play an important role in tumor growth and metastasis. This study examines the prognostic significance of two histological markers of angiogenesis, i.e., vascular cuffing (VC), a bead-like arrangement of microvessels closely surrounding microscopic tumor nests, and microvessel density (MVD), the number of microvessels in a unit area, in cervical squamous cell carcinoma. METHODS: One hundred twenty-two specimens from surgically resected uteri with cervical squamous cell carcinoma were histologically reviewed and immunostained for CD34. VC was graded into "none," "incomplete," and "complete." The MVD was determined by counting the microvessels with a light microscope within a x200 field area where neovascularization occurred most actively. Stromal inflammation was also split into three grades. The relationship of VC or MVD to clinicopathological prognostic factors such as FIGO stage, cervical stromal invasion, lymph-vascular space invasion, pelvic lymph node metastasis, and parametrial invasion was evaluated using univariate and multivariate analyses. RESULTS: The patients with a complete VC pattern showed a significantly worse prognosis compared to those with a pattern graded as either none or incomplete (P<0.011 and P<0.0001, respectively). The Cox regression analysis revealed the complete VC pattern, together with parametrial invasion, to be an independent prognostic indicator for overall survival. MVD and the grading of stromal inflammation showed no significant relationship with VC or overall survival. CONCLUSIONS: The complete VC pattern may therefore be a useful prognostic indicator in cervical squamous cell carcinoma.     

Angiogenesis of endometrial carcinomas assessed by measurement of intratumoral blood flow, microvessel density, and vascular endothelial growth factor levels

OBJECTIVE: To evaluate the relationship between blood flow in the tumor assessed by color Doppler ultrasound, microvessel density, and vascular endothelial growth factor levels in endometrial carcinoma. METHODS: Forty-nine patients undergoing surgery for endometrial carcinoma were enrolled. Transvaginal color Doppler ultrasound was performed preoperatively and the lowest resistance index (RI) in the tumor was recorded for analysis. Vascular endothelial growth factor in the tumor was quantified by enzyme immunoassay. The microvessel density of the excised tumor was assessed immunohistochemically. The relationships between the corresponding RI, microvessel density, and vascular endothelial growth factor level of the tumor tissues and clinical and pathologic parameters were analyzed. RESULTS: Significantly lower RIs were noted in tumors of stage II or greater (0.37 compared with 0.50, P <.001), of high histologic grade (grade 3) (0.34 compared with 0.49, P =.004), with deep myometrial invasion (one-half depth or greater) (0.39 compared with 0.49, P =.002), with lymphovascular emboli (0.38 compared with 0.49, P <.001), or with lymph node metastasis (0.30 compared with 0.49, P <.001) compared with stage I tumors and tumors of histologic grade 1 or 2, with superficial myometrial invasion, without lymphovascular emboli, or with no lymph node metastasis. Increased vascular endothelial growth factor levels and microvessel density (x200 field) also were detected in tumors of stage II or greater (975 compared with 129 pg/mg, P =.014; and 88 compared with 61, P =.018, respectively), with lymphovascular emboli (1138 compared with 120 pg/mg, P =.002; and 86 compared with 63, P =.023), or with lymph node metastasis (1011 compared with 95 pg/mg, P <.001; and 98 compared with 61, P =. 019). Resistance index, microvessel density, and vascular endothelial growth factor levels in the tumor showed linear correlations (RI compared with microvessel density: r = -.32, P =. 03; RI compared with vascular endothelial growth factor levels: r = -.40, P =.004; microvessel density compared with vascular endothelial growth factor levels: r =.36, P =.011). CONCLUSION: Blood flow assessed by color Doppler ultrasound has histologic and biologic correlations with angiogenesis and vascular endothelial growth factor levels and might play an important role in predicting tumor progression and metastasis in endometrial carcinoma.     

长链非编码RNA高表达与子宫内膜癌病理特征和预后关系的Meta分析

目的：分析长链非编码RNA（lncRNA）高表达与子宫内膜癌病理特征及预后的相关性，系统评价其对子宫内膜癌患者预后的预测价值。方法：计算机检索Pubmed、Embase、Web of Science、中国知网、万方和维普等数据库相关文献，检索时间为建库至2017年10月9日，根据制定的纳入和排除标准选择文献并进行质量评价，提取子宫内膜癌患者的病理特征和生存相关数据。应用Revman 5.3及Stata 12.0统计软件对数据进行合并分析。结果：共纳入9篇文献（其中1篇中文、8篇英文），包含775例子宫内膜癌患者。Meta分析结果显示，lncRNAs高表达与国际妇产科联盟（FIGO）分期（OR=2.41，95%CI：1.11～5.25，P=0.03）、组织学分级（OR=2.01，95%CI：1.19～3.41，P=0.009）、肌层浸润（OR=2.29，95%CI：1.16～4.51，P=0.02）及淋巴结转移（OR=4.00，95%CI：2.40～6.66，P＜0.000 01）均显著相关；与孕激素受体（PR）及雌激素受体（ER）阳性表达均无关（P＞0.05）；与lncRNAs低表达组比较，高表达组患者OS较短（HR=2.43， 95%CI：1.55～3.80）；亚组分析HOTAIR高表达与OS相关（HR=3.73，95%CI：1.21～11.49）。结论：lncRNAs高表达对子宫内膜癌患者的预后具有重要预测价值。lncRNAs表达越高、临床分期及组织学分级越高、肌层浸润越深，淋巴结转移风险亦增加，总生存期缩短，预后越差。     

Ovarian cancer p53 mutation is associated with tumor microvessel density

OBJECTIVE: The objective of this study was to investigate the relationship between microvessel density, as measured by CD31 staining, and histopathologic factors as well as p53 tumor suppressor gene mutation in ovarian cancer. METHODS: Ovarian cancers (n = 77) were analyzed for p53 gene mutations and CD31 immunohistochemical expression. Histopathologic and mutational data were related to CD31 staining utilizing the Mantel correlation statistic. The microvessel density was scored by averaging counts from three high-power (200x) fields. Survival was based upon maximizing the hazard ratio. RESULTS: The mean microvessel density counts based on CD31 staining (vessels/HPF) for each FIGO stage and mutation type are as follows: Stage I (10.2), Stage II (10.7), Stage III (13.8), Stage IV (22.0), wild-type p53 (9.3), missense p53 mutation (14.4), and null p53 mutation (23.1). There was a significant correlation between microvessel density count and FIGO stage (P = 0.026), grade (P = 0.04), and p53 mutation type (P = 0.02). Median survival was more than doubled (6.4 vs 2.9 years; P = 0.009) for tumors with microvessel density counts less than or equal to 14 vessels/HPF. CONCLUSIONS: These data are consistent with the hypothesis that ovarian cancer p53 mutation functions to directly influence angiogenesis, which in turn compromises disease-specific survival. It also suggests validity to targeting p53 alterations with gene replacement as well as the use of antiangiogenesis agents as novel molecular-based therapeutics for ovarian cancer.     

Prognostic factors of adenocarcinoma of the uterine cervix

OBJECTIVE: The prognostic importance of adenocarcinoma of the uterine cervix was investigated. Methods. One hundred ninety-three patients (144 had stage I disease, 41 stage II, and 8 stage III-IV) with invasive adenocarcinoma of the uterine cervix treated initially at the Aichi Cancer Center between 1964 and 1995 were studied. RESULTS: Of all the invasive cervical cancers, 8.8% were adenocarcinomas that had been increasing during the past decade. The overall 5-year survival for stage I was 88.8%, stage II 44.9%, and stage III-IV 0% In univariate analysis, the clinicopathological factors associated with overall survival and disease-free survival were age of patient, stage of disease, presence of nodal metastasis, number of lymph nodes involved, lymph-vascular space invasion, tumor size, and intraperitoneal metastasis. Multivariate analysis performed in all cases identified the clinical stage of disease, the presence of nodal metastasis, number of lymph nodes involved, lymph-vascular space invasion, and tumor size as the independent risk factors for recurrence and survival. In the analysis of stage I disease, lymph node metastasis and tumor size were the significant prognostic factors, while lymph-vascular space invasion and tumor size were the factors in advanced disease. Tumor grade and histological type were not associated with recurrence and survival. CONCLUSION: These results suggested the association of lymph node metastasis with the prognosis of early stage adenocarcinoma of the uterine cervix and lymph-vascular space invasion with the advanced stage. Tumor size was an independent risk factor throughout all stages.     

LGR5在子宫内膜癌中的表达及其意义

目的:探讨富含亮氨酸重复序列G蛋白偶联受体5(LGR5)在子宫内膜癌中的表达情况及其与临床病理因素的关系。方法:采用免疫组织化学SABC法检测90例子宫内膜癌及30例正常子宫内膜组织中LGR5表达情况,并分析其与临床病理因素的关系。结果:LGR5在子宫内膜癌组织中的阳性表达率(63.3%)显著高于正常子宫内膜(23.3%)(P0.001)。LGR5在1/2肌层浸润组的阳性表达率(72.5%)显著高于≥1/2肌层浸润组(33.3%)(P=0.001)。LGR5的阳性表达率在年龄、病理类型、组织学分级、宫颈累及、淋巴结转移、FIGO分期组间差异均无统计学意义(P0.05)。多因素分析发现LGR5是子宫内膜癌有无肌层浸润的独立影响因素(OR=0.163,95%CI 0.034~0.772,P=0.022)。结论:LGR5在子宫内膜癌组织中表达上调,提示与肌层浸润深度相关,可能在子宫内膜癌的发生中起一定作用。     

Angiogenesis, p53, and bcl-2 expression as prognostic indicators in endometrial cancer: comparison with traditional clinicopathologic variables.

We investigated the relation of expression of tumor-suppressor gene product p53, apoptosis-regulator gene product bcl-2, and CD34 (as a measure of microvessel density [MVD]) with traditional clinicopathologic prognostic variables in endometrial carcinoma (histologic type, grade, depth of myometrial invasion, angiolymphatic invasion, lymph node involvement). In specimens from 63 patients with endometrial carcinoma, the mean MVD (64.38+/-28.71 microvessels per 200x field) was not related to any clinicopathologic variables. Nuclear p53 expression was detected in 15 (23.8%) patients and was higher in nonendometrioid carcinomas (p<0.05) and in tumors with increasing histologic grade (p<0.001). Cytoplasmic bcl-2 staining was seen in 79.3% of the tumors. There was a negative correlation between bcl-2 expression and histologic type and tumor grade (p<0.05). In survival analysis, patient age, FIGO stage, high expression of p53, low expression of bcl-2, and high and intermediate MVD values were found to be the most significant prognostic indicators of survival (p<0.05). In multivariate regression analysis, FIGO stage and low bcl-2 expression were found to be the only independent indicators of prognosis (p<0.05).