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.     

Assessment of depth of myometrial invasion in endometrial adenocarcinoma

Depth of myometrial invasion in stage I adenocarcinoma of the endometrium is recognized as a prognostic factor for lymph node metastasis and overall survival. To determine if depth of myometrial invasion estimated by gross examination correlated with final histologic depth of invasion, we retrospectively reviewed all cases of surgical stage I endometrial adenocarcinoma treated at our institution between July 1985 and July 1988. Of the 113 evaluable patients, 63 had grade 1 lesions, 37 grade 2 lesions, and 13 grade 3 lesions. The depth of invasion was accurately determined by gross examination in 55 of 63 (87.3%) grade 1 lesions, 24 of 37 (64.9%) grade 2 lesions, and only 4 of 13 (30.8%) grade 3 lesions. Thus, gross examination of fresh tissue to estimate depth of myometrial invasion in endometrial adenocarcinoma is less reliable as the grade of the tumor increases. Alternative methods, such as frozen section, should be considered when evaluating depth of invasion, especially when this affects intraoperative decisions regarding lymph node sampling.     

An analysis of prognostic significance of new FIGO staging (1989) of endometrial cancer

Histopathologic factors were investigated in the data for ninety-one patients with endometrial carcinoma who were treated surgically. Each of these subjects was reclassified according to the new FIGO surgical criteria (1989) for stages and the relationship between the new classifications and the prognosis of patients was analyzed. One third of the patients (24/72) with clinical FIGO stage I (1983) had extracorporeal spread of the disease and these cases were reclassified as surgical stages II and III. Among clinical stage Ib patients there were many more with extracorporeal spread than among those in clinical stage Ia (p less than 0.005) although there was no difference between the histopathological characteristics (histologic grade, myometrial invasion, cervical involvement, adnexal involvement and pelvic lymph node metastasis) of the stage Ia and Ib groups. Univariate survival analysis revealed that the histologic grade (p less than 0.05), myometrial invasion (p less than 0.05), cervical involvement (p less than 0.005) and pelvic lymph node metastasis (p less than 0.005) correlated with the patient's prognosis. Multivariate survival analysis with the proportional hazard regression model showed that cervical involvement (p = 0.05) and the new stage classification (p = 0.03) correlated significantly with the prognosis. The cumulative 5-year survival rate by clinical stage (1983) was 87% for stage I (Ia: 96%, Ib: 80%) and 72% for stage II, between which no significant difference was determined. The survival rate for stage III was not calculated because there was only one case with stage III disease in this study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intratumoral blood flow characteristics and prognostic factors in patients with endometrial carcinoma

Purposes of the study were to evaluate the correlation between intratumoral blood flow and stage, histologic grade, depth of myometrial invasion and lymph node metastasis in endometrial carcinoma and to assess if vascular/lymphatic spaces invasion is predictable by Doppler ultrasound. Fifty-three patients with endometrial carcinoma were enrolled before surgical treatment. Transvaginal Color Doppler Ultrasound was performed to detect the areas of increased vascularity (≥3) and to record the lowest resistance index (RI) from the blood flow signals within the tumour. Formalin fixed, paraffin embedded pathology slides were reviewed by a senior pathologist to evaluate histologic grading, depth of myometrial invasion, presence of lymph node metastasis and vascular/lymphatic spaces invasion. The number of patients with positive lymph node metastasis was too small to perform any statistical evaluation. Significantly lower RI was noted in tumours of advanced stage (>FIGO Stage I), tumours with higher histologic grade (Grade 3) and with presence of vascular invasion. No correlation was found for myometrial invasion (>50%). A high number of vascular areas was positively correlated with all the prognostic signs. Assessment of tumour changes in vascularity using colour Doppler ultrasound provides useful information for the preoperative prediction regarding stage and histologic grade. The good correlation between Doppler ultrasound results and histological finding of vascular/lymphatic spaces invasion is another point in favour of routine colour Doppler studies in patients with endometrial carcinoma. We believe this technique is useful both for preoperative staging and that recording of tumour recurrence pattern may lead to early selection of those patients that need additional therapy. Received: 5 February 2001 / Accepted: 14 July 2001 Correspondence to P. Greco     

The relationship between mutant p53 gene, DNA contents and conventional clinicopathological prognostic variables in cases with endometrial carcinoma

PURPOSE OF INVESTIGATION: To determine whether p53 expression and DNA ploidy are related to traditional prognostic indicators in patients with endometrial cancer. METHODS: Tumor material (n=136) was analyzed regarding flow cytometric DNA ploidy and immunohistochemical p53 expression. Pearson's correlation, Fisher's exact test, Cox's regression analysis and the Kaplan-Meier survival test were used, as appropriate. RESULTS: P53 overexpression and DNA ploidy were higher in patients with nonendometrioid histology, FIGO advanced stage, poor grade, positive peritoneal cytology, lymphovascular space invasion (LVSI) and lymph node involvement (LNI). Histologic subtype, stage, grade, LVSI, LNI, tumor recurrence and overall survival rate correlated with p53 and DNA ploidy. No association of depth of myometrial invasion and age with p53 and DNA ploidy was observed. P53 was related to DNA ploidy. Of the factors analyzed, histologic subtype and myometrial invasion were found to be most important independent determinants of recurrence. Utilizing survival as the endpoint for multivariate analysis, when considering p53 and DNA ploidy together, histologic subtype, stage, peritoneal cytology, LNI and DNA ploidy were independent prognostic indicators. CONCLUSION: p53 expression and DNA ploidy were related to histologic subtype, FIGO stage, grade, LVSI, LNI, peritoneal cytology, tumor recurrence and overall 5-year survival. As compared to p53, DNA ploidy was the stronger independent predictor factor for survival. Neither p53 nor DNA ploidy were significant independent factors for tumor recurrence when submitted to multivariate analysis in this study. However, since p53 or DNA ploidy were found to be significant factors in univariate analysis and were correlated with tumor recurrence, they could be useful factors in making prognoses.     

冰冻病理诊断预测子宫内膜癌淋巴转移的临床价值研究

目的:研究影响子宫内膜癌患者淋巴结转移的因素,评价术中冰冻病理预测淋巴结转移的作用。方法:回顾分析1996年7月至2008年1月在上海交通大学医学院附属仁济医院和2008年9月至2011年9月在同济大学附属第一妇婴保健院收治的共389例子宫内膜癌患者的临床资料,195例患者实施了盆腔淋巴结切除,其中43例同时行腹主动脉旁淋巴结切除。分析患者淋巴结转移的临床相关因素,评价冰冻病理结果在预测淋巴结转移中的价值。结果:盆腔淋巴结转移率为12.8%(25/195),腹主动脉旁淋巴结转移率为11.6%(5/43)。深肌层浸润(P<0.001)、宫颈累及(P<0.001)、ER阴性(P=0.001)与盆腔淋巴结转移显著相关。肿瘤细胞级别升高、病理类型(Ⅰ型、Ⅱ型)与盆腔淋巴结转移无显著相关性。低风险子宫内膜癌(排除G3和肌层深度≥1/2)患者的盆腔淋巴转移率为4.5%(3/67)。按冰冻结果制定4种预测模型,G1+限于内膜组,淋巴结阳性率为0;G1+<1/2肌层组,盆腔和腹主淋巴结阳性率均为2.4%;G2+<1/2肌层组,盆腔和腹主淋巴结阳性率分别为4.8%、0;未发现G2+限于内膜的病例。淋巴结切除组的生存率高于未切除组(79.5%vs 75.9%),但无统计学差异(P=0.086)。结论:冰冻病理用于预测淋巴结转移的作用有限,建议对除G1限于内膜的子宫内膜样腺癌患者,其余均应实施全面的分期手术。     

Prognostic factors affecting disease-free survival in early-stage cervical cancer patients undergoing radical hysterectomy and pelvic-paraaortic lymphadenectomy

OBJECTIVE: This study was performed to identfy surgical and histopathologic prognostic factors that could predict 5-year disease-free survival (DFS) after patients underwent radical hysterectomy and pelvic-paraaortic lymphadenectomy for FIGO Stage I-II cervical carcinoma. METHODS: A retrospective review was performed for all patients undergoing primary radical hysterectomy and pelvic-paraaortic lymphadenectomy for Stage I-II cervical cancer at Ankara Oncology Hospital from 1995 to 2000. Clinical and pathologic variables including age, tumor size (TS), clinical stage, depth of invasion (DI), lymphovascular space involvement (LVSI), cell type, tumor grade, lymph node metastases (LNM), parametrial involvement, surgical margin involvement and pattern of adjuvant therapy were analyzed using univariate analyses. DFS was performed by the Kaplan-Meier method and the log-rank test. Independent prognostic and predictive factors affecting DFS were assessed by the Cox proportional hazard method. RESULTS: Ninety-three patients underwent primary type III radical hysterectomy and pelvic-paraaortic lymphadenectomy. Five-year DFS was 87.1%. LVSI, parametrial involvement and grade were the prognostic factors that independently affected survival. DFS was not significantly different for age, disease status of the surgical margins, tumor size, depth of invasion, cell type, pelvic lymph node metastases and adjuvant radiotherapy. CONCLUSIONS: LVSI, parametrial invasion and histologic grade 2-3 were independent prognostic factors in early-stage cervical cancer patients. Adjuvant radiotherapy in these patients provides no survival advantage.     

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, 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).     

Lymphvascular space involvement--a prognostic indicator in endometrial adenocarcinoma

The present study evaluates the effects of various prognostic indicators on survival of patients with clinical Stage I endometrial carcinoma. Ninety-three patients who were treated for clinical Stage I endometrial adenocarcinoma at Maimonides Medical Center from October 1979 to October 1987 had sufficient surgical-pathological information for retrospective surgical staging according to the new FIGO classification. Histology was reviewed. A new grade and surgical stage was assigned to each patient in accordance with the recent FIGO guidelines for surgical staging of corpus cancer. Poor prognostic indicators, namely, tumor grade, depth of myometrial invasion, peritoneal cytology, lymph node metastases, and lymphvascular space (LVS) involvement, were correlated with 5-year survival rates. Survival rates were calculated by the life table method. Depth of myometrial invasion, lymph node involvement, and peritoneal cytology had significant statistical correlation with poor survival. Positive finding of each of the prognostic indicators, including LVS involvement, was significantly associated with poor survival (all P less than 0.001). The value of these prognostic indicators in early endometrial carcinoma is discussed.     

Endometrial cancer: predictors of peritoneal failure

OBJECTIVE: To assess determinants of peritoneal failure in endometrial cancer patients after definitive primary treatment. METHODS: Of 599 patients with endometrial cancer who had primary surgery at our institution during the decade before 1994, 131 had relapse. We defined "peritoneal failure" as relapse when it occurred in the upper abdomen or involved the pelvic peritoneum (or both). Mean follow-up was 72.8 months. RESULTS: Peritoneal failure was detected in 37 of 599 (6%) patients and represented 28% of identified failures. Stage IV disease, cervical stromal invasion, adnexal involvement, myometrial invasion >50%, primary tumor diameter >2 cm, positive peritoneal cytology, lymph node metastasis, histologic grade 3, nonendometrioid histologic subtype, absence of associated hyperplasia, and lymphovascular invasion correlated significantly (P < 0.01) with peritoneal failure. However, on regression analysis, only stage IV disease (P < 0.001, relative risk [RR] = 7.53), nonendometrioid histologic subtype (P = 0.02, RR = 3.01), and cervical stromal invasion (P = 0.04, RR = 2.83) were independent predictors of peritoneal failure. Because 22 of 37 (59%) peritoneal failures were in patients with stage IV disease, we considered separately the 545 patients with stage I-III disease. On regression analysis, nonendometrioid histologic subtype (P < 0.001, RR = 11.58), positive peritoneal cytology (P = 0.009, RR = 6.72), lymph node metastasis (P = 0.02, RR = 5.10), and cervical stromal invasion (P = 0.04, RR = 3.10) were independent predictors of peritoneal failure. Of the 38 patients in whom at least two of these four predictors were positive, 26% had peritoneal failure at 5 years, compared with 1% of the 507 patients who had none or only 1 predictor (P < 0.001). CONCLUSION: Patients with stage IV disease and those with stage I-III disease and at least two of the four independent predictors (nonendometrioid histology, positive peritoneal cytology, cervical stromal invasion, and lymph node metastasis) would be candidates for new therapeutic trials incorporating surgical and adjuvant treatment targeting the entire abdominal cavity.     

子宫内膜癌腹膜后淋巴结转移相关因素分析

目的:探讨预测子宫内膜癌腹膜后淋巴结转移的指标,以期为确定子宫内膜癌手术范围提供参考。方法:回顾分析1997年1月至2006年12月初治为手术治疗的641例子宫内膜癌患者的临床与病理资料,单因素分析用χ2检验和Fish确切概率法,多因素分析用Logistic回归模型。结果:经多因素分析显示,病理分级G3、深肌层浸润、附件转移对预测子宫内膜癌盆腔淋巴结(pelvic lymph node,PLN)转移具有统计学意义;盆腔淋巴结转移与腹主动脉旁淋巴结(para-aortic lymph node,PALN)转移显著相关。结论:病理分级G3、深肌层浸润、附件转移是子宫内膜癌盆腔淋巴结转移的重要预测因素;盆腔淋巴结转移对预测腹主动脉旁淋巴结转移具有重要意义。病理分级G3、深肌层浸润、附件转移的子宫内膜癌患者应行盆腔淋巴结清扫术,并根据术中患者的盆腔淋巴结状况决定是否行腹主动脉旁淋巴结清扫术。     

Lymphovascular space involvement is the sole independent predictor of lymph node metastasis in clinical early stage endometrial cancer

Purpose

To determine clinicopathological risk factors associated with lymph node metastasis in endometrial cancer (EC).

Methods

Clinicopathological data of patients who underwent comprehensive surgical staging for clinical early stage EC between 2001 and 2010 at Hacettepe University Hospital was retrospectively reviewed.

Results

Two hundred and sixty-one patients were included. There were 26 patients (10.0 %) with lymph node metastasis. Of these, 14 (5.4 %) had pelvic lymph node metastasis, 8 (3.1 %) had both pelvic and paraaortic lymph node metastasis, and 4 (1.5 %) had isolated paraaortic metastasis. Univariate analysis revealed tumor size >2 cm, type II cancer, grade III histology, cervical stromal invasion, deep myometrial invasion, positive peritoneal cytology, adnexal involvement, serosal involvement, and presence of lymphovascular space involvement (LVSI) as significant clinicopathological factors associated with retroperitoneal lymph node metastasis. For paraaortic metastasis either isolated or with pelvic lymph node metastasis, significant factors were grade III disease, cervical stromal invasion, deep myometrial invasion, positive peritoneal cytology, adnexal involvement, serosal involvement, pelvic lymph node metastasis, and presence of LVSI. The only factor associated with isolated paraaortic lymph node metastasis was LVSI. Multivariate analysis revealed LVSI as the only independent factor for both retroperitoneal and paraaortic lymph node metastasis (odds ratio 14.9; 95 % confidence interval 3.8–59.0; p < 0.001, and odds ratio 20.9; 95 % confidence interval 1.9–69.9; p = 0.013, respectively).

Conclusion

Lymphovascular space involvement is the sole predictor of lymph node metastasis in EC. Therefore, LVSI status should be requested from the pathologist during frozen examination whenever possible to consider when a decision to perform or omit lymphadenectomy is made.     

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.     

Endometrial cancer: our experience

The Authors have referred to their experience based on 293 endometrial cancer patients operated at the II University Gynecological Clinic in Catania, between 1975 and 1989. Many prognostic indicators such as stage, histologic grade, myometrial invasion depth, lymph-node metastasis, non-neoplastic endometrium histology, tumor size and histology were studied; the Authors affirm the validity of two risk factors such as tumor size and the histology of the non-neoplastic endometrium, readily observable by hysteroscopy during the preoperative assessment and which are well correlated with the depth of myometrial invasion and lymph node methastasis.     

Correlation between clinical and histopathologic risk factors and lymph node metastases in early endometrial cancer (a multivariate analysis of 183 cases)

This study includes 183 patients with clinical stage I endometrial cancer subjected to peritoneal cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic and para-aortic lymphadenectomy and omental biopsy during a 12-year period in a single institution. The factors analyzed were age, menopausal state, cell type, grade, mitotic activity, myometrial invasion, lymphovascular space invasion, cervical involvement, microscopic vaginal metastases, adnexal metastases, peritoneal cytology, presence of concomitant endometrial hyperplasia and lymph node status. The overall incidences of pelvic and para-aortic lymph node metastases were found to be 15.3% (28/183) and 9.3% (17/183), respectively. In five of 17 patients (29.4%) with para-aortic nodal metastases, pelvic nodes were free of tumor. The most significant prognostic factors for positive pelvic and/or para-aortic nodes were found to be the depth of myometrial invasion, grade of tumor and age.     

Evaluation of the Prognostic Significance of nm23/NDP Kinase Protein Expression in Cervical Carcinoma: An Immunohistochemical Study

The objective of this study was to evaluate the prognostic significance of immunohistochemical staining for nm23/nucleoside diphosphate (NDP) kinase in cervical carcinoma. A retrospective analysis of 176 patients with cervical carcinoma FIGO stage IB treated with radical hysterectomy and pelvic lymphadenectomy from 1987 to 1990 was conducted. Immunohistochemical staining using the polyclonal nm23-H1/NDP kinase A antibody was correlated to various histopathological and morphological characteristics (tumor size, histologic type, grade of differentiation, vessel invasion, invasion into parametria, and lymph node metastasis) and relapse-free survival. For controls, sections were obtained from 10 hysterectomy specimens with normal cervical epithelium. Staining for nm23/NDP kinase was observed in 90% of control cases and in 70.5% of cases of cervical carcinoma, more frequent in squamous and adenosquamous cell carcinoma than in adenocarcinoma and more frequent in poorly differentiated than in more highly differentiated tumors. There were no differences related to size of tumor or invasion into vessels or parametria or occurrence of lymph node metastasis. The relapse-free survival was lower for patients with squamous cell and adenosquamous tumors with positive immunostaining for nm23/NDP kinase than for those with negative tumors when evaluated in univariate analysis. In multivariate analysis with tumor size, vessel invasion, invasion into parametria, grade of differentiation, and lymph node metastasis included, this difference was no longer significant. In patients with adenocarcinoma no difference was found. In conclusion, we did not find immunostaining for nm23/NDP kinase to be a useful indicator for prognosis in cancer of the uterine cervix.     

Endometrial tumor invasiveness is related to metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expressions

Matrix metalloproteinase (MMPs) expression has been linked to gynecological tumor aggressiveness. The objective of this study was to determine MMP-2, MMP-7, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 expression in endometrial malignancies and their relation to clinical and histologic parameters. Formalin-fixed, paraffin-embedded tumor samples from 50 patients with endometrial carcinoma treated between 1999 and 2004 were stained with specific monoclonal antibodies. The tumors were grouped according to the FIGO classification. The staining results were compared to histologic and clinical data. Semiquantitative analysis of MMP and TIMP expression showed a significant difference in TIMP-2 expression according to the histologic subtype (P = 0.03) and also a trend towards a difference in MMP-9 expression (P = 0.05). MMP-2 expression increased and TIMP-2 expression fell as the histologic grade increased (P = 0.0007, P < 0.0001, respectively). MMP-2 expression correlated with lymph node metastasis (P = 0.04), while TIMP-2 expression correlated with the depth of myometrial invasion (P = 0.01), vasculolymphatic space involvement (P = 0.02), and lymph node metastasis (P = 0.0003). These results support the involvement of MMPs and TIMPs in endometrial tumor growth and progression. High MMP-2 and low TIMP-2 expression were the most potent markers of endometrial tumors with a high risk of local and distant spread.     

Endometrial cancer: factors affecting survival

PURPOSE: To evaluate the influence in survival of clinical and pathological findings in patients with endometrial cancer. METHODS: In 152 women treated for endometrial cancer from 1982 to 1996, personal, obstetrical and oncological data, histology, grade, myometrial invasion, peritoneal cytology, FIGO stage and treatment were correlated with survival. RESULTS: Mean age was of 60.3 +/- 11.1 years old. Eight patients had a previous history of other neoplasms (seven of them gynecological). The mean clinical complaint was abnormal uterine bleeding. The most common histological type was endometrioid (84.9%), only 51 cases did not show myometrial invasion and 119 women were in Stage I at diagnosis. Peritoneal cytology was negative in 113 patients. Seven patients out of 85 in whom lymphadenectomy was performed showed metastasis. Seventeen of the patients died. The factors influencing survival were age, myometrial invasion and lymph node metastasis. CONCLUSION: Lack of myometrial invasion, absence of lymph node metastasis and age younger than 60 years seem to be the most significant predicting factors of survival.     

Steroid Hormone Receptor Content and Lymph Node Status in Endometrial Cancer

The purpose of this study was to correlate the steroid hormone receptor status in endometrial adenocarcinoma with tumor metastasis to the pelvic and para-aortic lymph nodes, and with other known prognostic variables which influence survival. Tumor samples from 85 patients with endometrioid adenocarcinoma, or adenocarcinoma with squamous differentiation of the endometrium who underwent complete surgical staging, were assayed for cytoplasmic steroid hormone receptors using a dextran-coated charcoal technique. Steroid hormone receptor content was correlated to lymph node status, along with other prognostic variables, such as patient's age, depth of myometrial invasion, tumor grade, and pelvic cytology. By univariate analysis, the likelihood of nodal involvement was associated with younger age and poorly differentiated tumors. Multivariate analysis revealed that age, tumor grade, and myometrial involvement added significant independent prognostic information. Estrogen or progesterone receptor content did not add independent prognostic information concerning lymph node status once other factors were controlled. Knowledge of estrogen and progesterone receptor binding status in adenocarcinoma of the uterus does not replace the prognostic information imparted by careful sampling of lymph nodes.