p53 staining as a prognostic indicator in endometrial carcinoma.

OBJECTIVE: To investigate p53 expression in endometrial cancer and its significance as a prognostic indicator. METHODS: Thirty-five consecutively surgically treated patients with endometrial cancer had their p53 expression studied by immunoperoxidase staining and quantified by lighted microscopic evaluation of the staining pattern. The determination of mean percentage of p53 expression was compared to prognostic indicators of endometrial cancer. RESULTS: p53 staining was detected in 20 of the 35 cases of endometrial carcinoma. Eleven of the 21 endometrioid tumors stained positive, while 9 out of 14 tumors with more aggressive histology stained positive for p53. If the grade I and II patients were taken into account as a whole, there was a statistically significant correlation (p<0.001) between the grade I and II patients and the grade III patients. The difference was statistically significant between stage I and III (p<0.05). The difference between lymphovascular space invasion and no lymphovascular invasion and p53 positivity was statistically significant (p<0.05). CONCLUSION: p53 expression is more common in more aggressive histologic subtypes than in endometrioid adenocarcinomas. Strong expression of p53 correlates with advanced stage and high grade and is detected more frequently in endometrial cancers with lymphovascular invasion.     

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.     

p53 Expression as a Prognostic Indicator of 5-Year Survival in Endometrial Cancer

BACKGROUND: One of the most common genetic alterations to occur in human cancers is an alteration of the p53 tumor suppressor gene. The purpose of this article was to build upon the authors' previous work with p53 and determine whether p53 was a prognostic indicator of 5-year survival. METHODS: One hundred thirty-seven consecutively surgically treated patients with endometrial cancer had their p53 expression studied by immunoperoxidase staining and quantified by image analysis. All patients were evaluable for 5-year survival. RESULTS: One hundred three patients had endometrioid adenocarcinoma; 6, adenosquamous carcinoma; 14, papillary serous carcinoma; 10, clear cell carcinoma; and 4, undifferentiated carcinoma. p53 expression ranged from 0.0 to 58.2% positive nuclear area with a mean of 11.5% (median 2.6%) for the cohort. For the patients with endometrioid carcinoma, the mean p53 expression was 7.1% while for the nonendometrioid tumors it was 24.6% (P<0.001). Fifty-nine of the 103 endometrioid tumors (57.3%) stained positive for p53 while 32 of the 34 nonendometrioid (94.1%) tumors stained positive (P<0.001). Increasing histologic grade correlated with an increasing p53 expression (P = 0.003). The percentage of tumors expressing p53 was found to be higher in FIGO stage II, III, and IV than in FIGO stage I cancer (P = 0.003). However, mean p53 expression did not differ between early (stage I) and advanced (stage II, III, and IV) cancers (P = 0.088). Utilizing 5-year survival as the endpoint for multivariate analysis, FIGO stage (P = 0.0028) and p53 expression (P<0.001) were the only independent prognostic indicators found. CONCLUSION: p53 expression is more commonly found in nonendometrioid than in endometrioid adenocarcinoma of the endometrium. It, along with FIGO stage, is an independent prognostic indicator of 5-year survival.     

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.     

RECK与MMP-9基因在子宫内膜癌中的表达及临床意义

目的:研究RECK和MMP-9在不同子宫内膜组织中的表达,探讨两者在子宫内膜癌的发生、发展和浸润转移中的作用。方法:应用链霉菌抗生物素蛋白-过氧化酶(SP)免疫组化法检测42例子宫内膜癌组织、15例子宫内膜不典型增生组织及26例正常增生期子宫内膜组织中RECK蛋白及MMP-9蛋白表达情况。结果:与正常增生期子宫内膜组织及子宫内膜不典型增生组织相比,子宫内膜癌组织中RECK蛋白阳性表达率显著降低(χ2=9.307,P<0.05),MMP-9蛋白阳性表达率显著增高(χ2=11.438,P<0.05),RECK蛋白与MMP-9蛋白在子宫内膜癌中的表达存在明显负相关(P<0.01)。RECK蛋白的表达水平与临床分期、组织学分级、肌层浸润深度及淋巴结转移密切相关(均P<0.05);MMP-9蛋白的表达水平与临床分期、组织学分级、肌层浸润深度密切相关(均P<0.05),而与淋巴结转移无关。结论:RECK蛋白的表达缺失和MMP-9的表达可能与子宫内膜癌的发生、发展及浸润转移有关。     

子宫内膜癌bcl-2癌基因的持续性表达及其临床意义

目的：研究子宫内膜癌ｂｃｌ－２癌基因的表达及其临床意义。方法：采用免疫组化ＡＢＣ法检测增生期、分泌期、单纯型增生、复合型增生及不典型增生子宫内膜共２６份，子宫内膜癌４９例的ｂｃｌ－２癌基因蛋白表达及雌、孕激素受体（ＥＲ、ＰＲ）的表达。结果：正常增生期子宫内膜、增生的子宫内膜存在ｂｃｌ－２的表达，与ＥＲ相关，分泌期子宫内膜ｂｃｌ－２表达下降；４９例子宫内膜癌中２６例ｂｃｌ－２表达阳性，占５３％，２９例ＥＲ表达阳性，占５９％，２５例ＰＲ表达阳性，占５１％。７２％ｂｃｌ－２表达阳性者ＥＲ阳性，７５％ｂｃｌ－２表达阴性者ＥＲ阴性（Ｐ＜０．０１）。６８％ｂｃｌ－２表达阳性者ＰＲ阳性，６２％ｂｃｌ－２阴性者ＰＲ阴性（Ｐ＜０．０５）。子宫内膜癌Ｇ１、Ｇ２级ｂｃｌ－２的表达率为６６％，显著高于Ｇ３级者（２１％）（Ｐ＜０．０５）。ｂｃｌ－２的表达与肌层浸润、手术分期无关，ｂｃｌ－２表达阳性及阴性者生存率统计差异无显著性。结论：子宫内膜ｂｃｌ－２的持续性表达与卵巢激素相互作用可能在子宫内膜癌发生、发展中起作用     

p53 and bcl-2 in epithelial ovarian carcinoma: their value as prognostic indicators at a median follow-up of 60 months

OBJECTIVE: p53 is the most common tumor suppressor gene involved with human malignancies. Mutations in p53 are present in approximately 50% of human malignancies. bcl-2 is a protooncogene. Expression of its protein product is related to better prognosis in several malignancies. METHODS: One hundred and three patients with epithelial ovarian carcinoma were studied. Immunohistochemical staining using the pAb1801 monoclonal antibody to p53 and the anti-bcl-2 124 monoclonal antibody to bcl-2 was performed. Image analysis was used to measure percentage positive nuclear area staining of mutant p53. In addition to bcl-2 and p53, FIGO stage, grade, histology, and level of cytoreduction were analyzed as prognostic factors. Univariate as well as Cox regression analysis was performed. RESULTS: One hundred and three patients were followed for a mean of 60 months. Twenty patients had FIGO stage I disease, 4 stage II, 59 stage III, and 20 stage IV. Immunohistochemical staining for mutant p53 was not significantly related to DNA index (P = 0.99) but was related to increasing FIGO stage (P < 0.001) and increasing histologic grade (P = 0.039). Using Cox regression analysis, increased mutant p53 staining was an independent predictor of survival in these patients (P = 0.0032), along with stage (P < 0. 0001) and level of cytoreduction (P < 0.0001). Although by itself bcl-2 was not an independent prognostic indicator (P = 0.18), the combination of p53 and bcl-2 was independently predictive of survival (P = 0.038). CONCLUSION: This study confirms the authors' earlier report on the importance of p53 as a prognostic indicator of survival in ovarian carcinoma. Cox regression analysis reveals mutant p53 staining to be a better independent indicator of prognosis and survival in patients with ovarian carcinoma than the combination of bcl-2 and p53.     

The prognostic importance of proliferative activity and oestrogen receptor expression in stage I endometrial carcinomas.

The purpose of this study was to evaluate the prognostic significance of steroid hormone receptor proliferation index in endometrial adenocarcinoma. In this study, the correlation between oestrogen receptor expression, proliferation index and FIGO grade, age, myometrial invasion, tumour size and menopause status was evaluated in 40 patients with endometrial carcinoma. For this purpose, all tumours were stained immunohistochemically with oestrogen receptor and Ki-67 monoclonal antibodies. Oestrogen receptor expression and proliferation indices were found to be statistically associated with grade, age, menopausal status, vascular invasion and tumour size ( p < 0.001). Quantitative assessment of tumour proliferation and expression of oestrogen receptor were found to be important prognostic indicators in endometrial adenocarcinoma.     

Immunohistochemical bcl-2 expression, p53 overexpression, PR and ER status in endometrial carcinoma and survival outcomes

Immunohistochemical expression of bcl-2, p53, PR and ER in cases with endometrial carcinomas arrayed on a tissue microarray (TMA) was tested and correlated with clinicopathologic features, overall survival (OS), cancer-related survival (CRS) and disease-free survival (DFS). Seventy-seven patients with endometrial cancer were reviewed. Slides were evaluated by two pathologists blinded to patient clinical characteristics and survival data. Mean age of patients was 62.5 years (range 35-80), median follow up 60 months (range 9-120). Seventy-nine percent of patients were FIGO Stage I; 39% of the cases showed bcl-2 cytoplasmic staining and its expression was significantly correlated with low-grade tumor differentiation and age < or = 60 years. Nuclear p53 overexpression was detected in 23.4% of the cases and was significantly correlated with advanced stages (IIB-IV), non-endometrioid histology, nodal metastasis and advanced age (> 60 years). PR and ER were positive in 63.6% and 30% of the cases, respectively. Analysis of p53 overexpression and bcl-2 expression in relationship with PR and ER status showed a direct correlation between bcl-2 expression and PR positivity (p = 0.001). In a multivariate analysis FIGO staging was the only clinicopathologic parameter independently correlated with DFS. In conclusion p53 overexpression was directly associated with unfavorable clinicopathologic factors such as advanced stage, histologic subtype, advanced patient age and nodal metastasis. Bcl-2 expression was related with younger age, favorable grade and PR expression by tumor cells. Patient survival was not related to the tested biomarkers.     

p53 overexpression as a prognostic indicator in endometrial carcinoma

PURPOSE: To investigate the prognostic value of p53 overexpression in endometrial adenocarcinoma cases of different stages and histologic subtypes. METHODS: One hundred and eleven surgically staged endometrial carcinoma (EC) cases from 1996 to 2000 constituted this retrospective study group. Prognostic factors determined through the evaluation of surgery specimens by co-author pathologist, were surgical stage, tumor size, histology, histologic and nuclear grade, myometrial invasion, adnexal/serosal metastasis, peritoneal cytology, retroperitoneal lymph node involvement p53 overexpression was assessed via immunohistochemical staining. Tissues that expressed p53 were considered as positive p53 staining. In terms of degree of staining, 1-29%, 30-90% and 80-100% of tumoral tissue stained with p53 were considered to be mild, moderate and high p53 staining, respectively. RESULTS: Mean age and follow-up period of the study group were 58.2 +/- 10.6 years and 33.4 +/- 2.7 months, respectively. Percentages of cases surgically staged as early (I-II) and advanced (III-IV) FIGO stages were 65.8% (n: 73) and 34.2% (n: 38), respectively. Cases with positive p53 staining had a significantly high mean survival period compared with those with negative p53 staining (86.6 +/- 6.0 vs 49.1 +/- 8.1, p < 0.001). p53 overexpression was statistically detected to be high in Stage III-IV tumors, non-endometrioid histologic subtypes (p = 0.019), histologic and nuclear grade 2-3 tumors (p < 0.001), adnexal/serosal metastasis (p = 0.001), lymph node involvement (p = 0.012), and positive peritoneal cytology (p = 0.017). The degree of p53 staining was remarkably correlated with survival. In cases with mild and high p53 staining, mean survival times were 47.1 +/- 7.0 months and 57.0 +/- 13.1 months, respectively (p = 0.0003) compared to those with high p53 staining. On univariate analysis, all of the prognosticators, including p53 staining (p < 0.001) and degree of p53 staining (p < 0.001) appeared to be independent risk factors for poor prognosis. On multivariate analysis, only pelvic lymph node involvement (p = 0.03), serosal/adnexal involvement (p = 0.004), and positive peritoneal cytology (p = 0.01) were found to be independent prognosticators of survival while p53 expression (p = 0.743) and degree of p53 staining (p = 0.802) were not detected as independent prognosticators. CONCLUSION: p53 overexpression is strongly related to poor prognostic indicators in endometrial adenocarcinoma. Although in this study p53 overexpression was not detected as an independent prognosticator, additional studies with large data set are needed to evaluate the prognostic value of p53 expression.     

Combined E-cadherin, α-catenin, and β-catenin expression is a favorable prognostic factor in endometrial carcinoma

Cell adhesion molecules, such as epithelial cadherin (E-cadherin), might be involved in the processes of tumor invasion and differentiation. The aim of this study was to investigate the expression of E-cadherin, alpha-catenin, and beta-catenin in endometrial carcinoma and to determine the prognostic value of these factors. We have investigated the expression of E-cadherin, alpha-catenin, and beta-catenin by immunohistochemistry in 225 endometrial carcinomas. The correlation between the E-cadherin and the catenins and their correlation with several histologic and clinical parameters were analyzed. Negative E-cadherin, alpha-catenin, and beta-catenin expression was observed in 44%, 47%, and 33% of endometrial carcinomas, respectively, and was correlated with histologic FIGO grade 3 (P < 0.001). Negative E-cadherin expression was more often observed in nonendometrioid endometrial carcinomas (NEECs) than in endometrioid carcinomas (75% versus 43%; P= 0.04). Combined positive E-cadherin, alpha-catenin, and beta-catenin expression was an independent positive prognostic factor for survival in patients with grade 1-2 carcinomas (P= 0.02). Negative E-cadherin expression was found to be associated with histologic grade 3 and with NEEC. Combined positive E-cadherin, alpha-catenin, and beta-catenin expression was a significant prognostic factor.     

基于TCGA数据库分析KIF20 A在子宫内膜癌中的表达和意义

目的:检测驱动蛋白家族成员20A(KIF20A)在子宫内膜癌中的表达及其预后价值.方法:下载癌症基因组图谱(TCGA)中子宫内膜癌组织和癌旁组织样本的基因表达谱数据和临床数据,比较KIF20 A在子宫内膜癌组织和癌旁组织中的表达,并检测KIF20 A表达水平与患者生存预后的关系.结果:子宫内膜癌组织中KIF20 A表达...     

The association between p53 expression, stage and histological features in endometrial cancer

OBJECTIVE: Alterations of the p53 gene have been widely suggested to be relevant to the development of endometrial carcinoma. However, contradictory results have been reported when immunohistochemical determination of p53 expression has been correlated with stage and histological features of the tumours. STUDY DESIGN: Pathology findings were reviewed and p53 immunoperoxidase staining was performed in 240 cases of endometrial carcinoma. RESULTS: Uterine papillary serous adenocarcinomas showed significantly higher p53 overexpression than uterine endometrioid adenocarcinomas (100.0% versus 61.0%, p<0.005). p53 overexpression was significantly higher in the secretory variant (85.7%) than in the typical endometrioid carcinoma (60.0%) (p<0.05). p53 expression did not differ between early (stage I) and advanced (stage II-IV) carcinomas. Likewise, no difference was observed in p53 expression among different architectural grades. The incidence of metastasis to lymph nodes was similar in p53 positive (13.7%) and in p53 negative tumours (12.5%). CONCLUSION: In the present series, p53 immunostaining did not differ between cases with different FIGO stages or histologic characteristics of the tumours. No simple relationship exists between the immunohistochemical determination of p53 expression and the biological aggressiveness of endometrial carcinomas.     

Hypoxia contributes to development of recurrent endometrial carcinoma

Tumor hypoxia can trigger the induction of angiogenesis. High microvessel density (MVD) as well as hypoxia-inducible factor-1alpha (HIF-1alpha) have been related to recurrent disease and tumor aggressiveness, respectively. In this study, MVD and hypoxic status were investigated in primary and recurrent endometrial carcinomas. A total of 65 primary tumors of patients with recurrent endometrial carcinoma (n = 40), and without recurrent endometrial carcinoma (n = 25) were studied. Immunohistochemical analysis was performed on paraffin-embedded tumor tissue. MVD was determined by quantitative analysis of CD31/FVIII positive vessels. Tumor hypoxia was estimated by evaluating the expression of the hypoxia-regulated gene HIF-1alphaand its target gene carbonic anhydrase IX (CA-IX). An additional 23 recurrent tumors were available for determination of MVD and HIF-1alpha expression. Effects of hypoxia on tumor protein p53 (TP53) expression were evaluated in the endometrial cancer cell lines (ECC-1), Ishikawa (derived from adenocarcinomas), and AN3CA (derived from a lymph node metastasis). MVD, CA-IX, and HIF-1alpha expression were not significantly different in primary tumors of patients with recurrence compared to the control tumors. The MVD was significantly lower, and HIF-1alpha expression was significantly higher in recurrent tumors when compared with their primary tumors (paired t test, P < 0.05). HIF-1alpha expression correlated well with TP53 expression levels in primary tumors, but not in recurrences. TP53 protein levels were highest in AN3CA cells. Hypoxic conditions induced TP53 protein in ECC-1 and Ishikawa, but not AN3CA cells. We conclude that MVD, CA-IX, and HIF-1alpha expression are not independent prognostic markers for recurrent endometrial carcinoma. The low MVD, increased HIF-1alpha protein levels, dissociation of hypoxia, and TP53 protein induction in the metastatic tumor cells (AN3CA) support a role for hypoxia in the development of recurrent endometrial carcinoma.     

Prognostic importance of the nuclear proteins p53 and Rb in conjunction with DNA, nuclear morphometry and grading in endometrial carcinoma

In a series of 227 cases of endometrial carcinomas in FIGO stages I–IV, treated during the years 1984–89, immunohistochemical staining for the protein products of the two tumor suppressor genes p53 and retinoblastoma (Rb) were evaluated as prognostic factors with regard to tumor stage, FIGO grade, nuclear grade, morphometric nuclear parameters, DNA ploidy and S-phase fraction. Long-term survival analyses were endpoints and the Cox multivariate technique was used to evaluate the prognostic factors. In 20% of the cases p53 was positive. This was a genuine high-risk group associated with primary advanced carcinoma, nonendometrioid histology, poorly differentiated tumors, severe nuclear atypia, DNA aneuploidy, primary persistent tumors, recurrent tumors and a poor long-term survival rate (37% 5-year survival). In patients dying of their disease, 54% of the tumors stained positive for p53, compared with only 10% of the tumors not killing their hosts. Positive p53 staining was more common in older women. A pathologic Rb status (negative staining) was recorded in 6% of the cases. The Rb factor had only a minor influence on long-term survival and was not significant in multivariate analyses. The p53 staining status was the second most important prognostic factor after the nuclear grade in Cox multivariate analyses, after correcting for stage and age. Immunohistochemical staining for p53 protein should be included among previous available and important prognostic factors in endometrial carcinoma.     

The value of epithelial membrane antigen overexpression in hyperplastic and malignant endometrium and its relationship with steroid hormone receptor expression

The aim of this study was to evaluate the value of epithelial membrane antigen overexpression (EMA OE) in benign, hyperplastic and neoplastic endometrium and to analyze its association with estrogen and progesterone receptors (ER, PR) immunohistochemistry, tumor grade and myometrial invasion in patients with endometrial carcinoma (EC). The OE of EMA was analysed immunohistochemically in nine patients with benign endometrium (BE), in 18 patients with atypical complex endometrial hyperplasia (ACH) and in 29 patients with EC. EMA OE was present in 13 of 29 patients (44.8%) with EC, in two of 18 patients (11.1 %) with ACH, and in none of nine patients with BE (p < 0.05). EMA OE of endometrial carcinoma was statistically correlated with the International Federation of Gynecology and Obstetrics (FIGO) grade (G1 vs G2 and G3, p < 0.05) and depth of myometrial invasion (< 1/2 vs > 1/2, p < 0.05). EMA OE was significantly associated with PR negativity (p < 0.001). However it did not show any association with ER immunohistochemistry (p = 0.14). PR immunohistochemistry had significant correlations with FIGO grade (p < 0.001) and depth of myometrial invasion (p < 0.05) but ER loss showed a nearly significant association only with advanced FIGO grade (p = 0.054). In conclusion, EMA shows increased expression as the lesion progresses to malignancy and can also aid discrimination between hyperplastic and neoplastic states. The correlation of imunohistochemical findings with tumor grade and myometrial invasion could help in predicting behavior of the tumor and planning treatment in patients with endometrial carcinoma.     

Interpretation of p53 immunoreactivity in endometrial carcinoma: establishing a clinically relevant cut-off level.

There is accumulating evidence that immunohistochemical staining for p53 can identify patients with endometrial carcinoma who have an adverse outcome, but the interpretation of existing data is complicated by differences between studies in the way that p53 immunohistochemistry results have been assessed. In this study, we sought to determine the appropriate cut-off level for stratification of patients with endometrial carcinoma into high- and low-risk groups, based on p53 immunohistochemical staining. A total of 200 cases of endometrial carcinoma treated by hysterectomy were retrieved from the archives of the Department of Pathology, Vancouver General Hospital, from the period 1983 to 1998. Follow-up information was available for all cases. Slides were reviewed and the diagnosis confirmed, tumors graded according to FIGO grading system, and tumor cell type assessed. A tissue microarray consisting of duplicate 0.6-mm cores of tumor was constructed and immunostained for p53. Immunoreactivity for p53 was scored by counting the number of positively stained tumor cell nuclei and expressing this as a percentage of the total number of tumor cell nuclei counted (p53 index). Kaplan-Meier survival curves were constructed and compared by calculation of log-rank statistic, and multivariate analysis was performed by Cox regression modeling. The distribution of p53 index results was bimodal, with most cases having a very low or very high p53 index. The peaks of the bimodal distribution were clearly separated using a p53 index of > or =50%. Immunoreactivity was a significant adverse prognostic indicator of disease-specific survival (p<0.0001 by univariate analysis). Patients with strongly p53 immunoreactive tumors (p53 index >or =50%) had a significantly worse outcome than patients with weakly immunoreactive (p53 index > or =5% and <50%) or p53-negative (p53 index <5%) tumors (p = 0.0001). There was no significant difference between the outcomes for patients in the latter two groups. By multivariate analysis, p53 overexpression was a significant prognostic indicator independent of patient age and tumor stage (p = 0.008) but was not independent when the analysis was extended to include FIGO grade and tumor cell type. p53 immunostaining was of prognostic significance in the subset of patients with endometrioid carcinomas (p = 0.02), but not in patients with clear cell or papillary serous carcinomas. Using a p53 index of > or =50% as a cut-off between positive and negative p53 staining, immunohistochemical staining for p53 is a prognostic indicator in patients with endometrial carcinoma of endometrioid type. p53 immunostaining was not found to be of prognostic significance independent of tumor cell type and grade.     

Postoperative radiotherapy in endometrial carcinoma: analysis of prognostic factors in 440 cases

PURPOSE: The aim of this study was to determine the prognostic factors influencing overall, disease-free and local recurrence-free survival in patients treated postoperatively with adjuvant radiotherapy for endometrial carcinoma. METHODS: The records of 440 patients with endometrial carcinoma treated by postoperative radiotherapy between January 1985 and June 1997 were reviewed retrospectively. All patients received postoperative external radiotherapy with 1.8-2.0 Gy daily fractions up to 36-68 Gy (median 54 Gy). Intracavitary brachytherapy was applied to 61.8% of the cases. Survival analysis was performed using the Kaplan-Meier method. The log-rank test was used for univariate analysis and the Cox regression model for multivariate analysis. RESULTS: Median age of the patients was 57 (range: 35-83). Histologically 80.2% were adenocarcinoma, 5.7% adenosquamous carcinoma, 5.2% clear-cell carcinoma and 4.3% serous papillary carcinoma. The distribution by stages were: 62.2% Stage I, 20.0% Stage II, 14.9% Stage III, 2.8% Stage IV. Median follow-up time was 53 months (7-173 months). Total failure rate was 15.2% with 2.7% of patients having only local failure, 2.0% local and distant failure and 10.5% distant failure only. Five-year overall, disease-free and local recurrence-free survival rates were 81.6%, 80.7% and 94.6%, respectively. According to univariate analysis prognostic factors influencing disease-free survival were histologic type (p=0.0067), histologic grade (p=0.0015), stage (p<0.0001), myometrial invasion (p<0.0001), peritoneal cytology (p=0.0013) and cervical involvement (p=0.0106) while the prognostic factors affecting local recurrence-free survival were stage (p=0.0277), myometrial invasion (p=0.0054), peritoneal cytology (p=0.0427). According to multivariate analysis prognostic factors influencing disease-free survival were histologic type (p=0.0194), myometrial invasion (p=0.0021), and histologic grade (p=0.0303) while the only prognostic factor influencing local recurrence-free survival was myometrial invasion (p=0.0241). CONCLUSION: Radiotherapy is a highly effective adjuvant treatment providing an excellent locoregional control rate and it should be continued for patients with unfavorable prognostic factors.     

A study of heat shock protein 27 in endometrial carcinoma

OBJECTIVE: Heat shock protein 27 (HSP27) is a relatively small protein produced in response to pathophysiologic stress. The purpose of this study was to determine prospectively whether HSP27 was associated with known prognostic factors in patients with endometrial carcinoma. METHODS: One hundred fifty-three consecutive patients with endometrial carcinoma were studied. Slides were prepared from fresh tissue. HSP27 was analyzed using a semiquantitative measurement. Patient records were examined for FIGO stage, grade, depth of myometrial invasion, histology, lymphovascular space invasion, time to recurrence, and survival. RESULTS: The mean follow-up was 53 months (median 56 months, range 30-68 months). Endometrioid tumors showed significantly higher HSP27 staining than nonendometrioid tumors (P = 0.005). Patients alive at the conclusion of this study had significantly higher mean HSP27 staining than patients who were deceased (P < 0.001). Logistic regression revealed HSP27 staining (P = 0.02), FIGO stage (P = 0. 014), and lymphovascular space invasion (P = 0.046) to be independently predictive of survival. CONCLUSION: HSP27 staining is significantly higher in endometrioid than nonendometrioid tumors. HSP27 staining is an independent prognostic indicator in patients with endometrial carcinoma, the most common gynecologic malignancy in the United States.     

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.