Degree of DNA ploidy and steroid hormone receptors as prognostic factors in endometrial carcinoma]

In a prospective investigation the concentration of DNA (ploidy) and of steroid hormone receptors (ER and PgR, resp.) were studied in endometrial carcinoma and related to each other, to established morphological prognostic criteria (stage, typing, grading, relative invasion of myometrium), and to the clinical progress of disease, respectively. The microscopic spectrophotometric analysis of DNA showed diploid main lines in 2/3 of investigated endometrial carcinoma. It could be demonstrated a relationship between heteroploidy, decreased mean concentrations of ER and PgR, unfavourable prognostic factors (stage II-IV, G3, myometrial invasion of greater than 2/3) and clinical progress of disease. The mean value of ER and PgR was higher in diploid carcinoma than in heteroploid ones. Significant differences were found both in the relation of the PgR concentration to different tumor stages (stage I vs. II-IV) and of the concentration to the different types of ploidy. Exceeding the histological differentiation, the determination of DNA and ER/PgR receptors can results in additional prognostic informations for a scientific proved, adjuvant or curative strategy of therapy after the operation.     

Nuclear morphometry and DNA flow cytometry as prognostic methods for endometrial carcinoma

In a series of 227 women with endometrial carcinoma stages I–IV the prognostic value of nuclear morphometry and DNA analysis was evaluated prospectively. The tumors were also classified according to histologic subtype, degree of differentiation (FIGO), and nuclear grade. The DNA analysis (ploidy and S-phase fraction) was made using flow cytometry on fresh-frozen tissue. The morphometric measurements and the grading of the tumors were done on both fresh-frozen tissue and on formalin-fixed and paraffin-embedded tissue. The rate of recurrence for the complete series was 14% with 2.2% vaginal metastases. The overall 5-year survival rate was 68% and the corrected survival rate 76%. The minimum nuclear diameter and the standard deviation (SD) of the maximum nuclear diameter were significant and independent prognostic variables in a Cox multivariate analysis when analyzed on paraffin-embedded tissue. The nuclear grade was the single most prognostically informative variable. A corresponding analysis on fresh-frozen tissue showed that the S-phase fraction and the FIGO grading of the tumor were significant variables. The morphometric variables and the nuclear grading were non-significant prognostic variables. Morphologic changes in tumor cell nuclei during the freezing and thawing procedures may explain the loss of prognostic information. A combination of DNA index (fresh-frozen tissue) and the mean values of the shortest nuclear diameter and the SD of the longest diameter (paraffin-embedded tissue) gave the best prognostic information vis-a-vis cancer-related death in an all-possible-subsets regression analysis.     

DNA content as a prognostic factor in endometrial carcinoma

Two hundred thirty-three cases of endometrial carcinoma were analyzed for DNA content using flow cytometry of cell nuclei extracted from archival paraffin blocks. The median follow-up time for the cases was 8.7 years. Aneuploidy, present in 18% of tumors overall, was associated with adverse histologic type, high grade, and depth of invasion in the uterus. Aneuploidy was not detected in low-grade carcinomas. A DNA index greater than 1.5 strongly predicted death from disease. For endometrial adenocarcinoma and papillary serous carcinoma, this finding appeared independent of stage or tumor grade. The percentage of cells in S phase or G2 + M of the cell cycle did not predict clinical outcome in diploid tumors. Application of DNA analysis to low-stage endometrial cancers of high grade or of papillary serous type may be useful for selecting a subgroup of patients for adjuvant therapy.     

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.     

DNA ploidy and steroid receptors as predictors of disease course in patients with endometrial carcinoma

Prognostic factors for outcome of malignant disease should be based on objective assessments whenever possible, so that the results may be reproduced. In a prospective study, tumor samples from 75 patients were subjected to flow cytometric DNA analysis. Samples were also taken from 61 patients for estradiol and progesterone receptor measurements. The course of the disease was analysed with regard to ploidy and receptor status. Receptor status was significantly correlated with ploidy, as diploid tumors were more often receptor-positive or receptor-rich (greater than or equal to 30 fmol/mg protein). Mortality and recurrence rates were highest among patients with aneuploid or receptor-poor tumors. Ploidy, receptor status, histological grade, surgical stage, and myometrial invasion were found to be of significant prognostic value. By multivariate analysis, ploidy was indicated to be the best predictor, followed by surgical stage. DNA and receptor measurements are recommended in research on endometrial carcinoma, and may become useful in routine clinical work.     

DNA ploidy level as prognostic factor in low stage carcinoma of the uterine cervix

Flow cytometry was used to measure DNA content of tumor cells in paraffin-embedded archival material from 89 patients with squamous cell carcinoma of the cervix uteri stages IB and IIA. Patients were all treated with radical hysterectomy and transperitoneal lymphadenectomy. Twenty-four percent received radiotherapy postoperatively because of tumor spread into parametria or positive lymph nodes. Ploidy grade was compared to other prognostic factors. DNA-aneuploidy was seen in 44 (49%), DNA-diploidy in 16 (18%) and 29 (33%) of the tumors were DNA-periploid. Sixty-nine (78%) patients were in FIGO stage IB, 20 (22%) in IIA. In 19 (21%) lymph node metastases were found, vasoinvasion in 25 (28%). Overall disease-specific 5-year survival was 80%. There was a significant effect of positive lymph nodes (90% vs 47%) and vasoinvasion (87% vs 64%) on the 5-year survival (resp. P less than 0.01 and P = 0.02). No correlation was found between stage (81% for IB vs 80% for IIA) or DNA-ploidy grade (81% for aneuploidy, 82% for periploidy, 79% for diploidy) and survival (resp. P = 0.9 and P = 0.8). Ploidy grade was equally divided over other prognostic factors. In stepwise Cox regression analysis DNA-ploidy grade showed no independent effect on survival. We conclude that DNA flow cytometry in this material was of no additional prognostic value.     

影响分段诊刮诊断子宫内膜癌细胞病理分级准确率的临床因素分析

目的:比较分段诊刮和术后子宫病理判断子宫内膜癌肿瘤病理分级的符合率,探讨影响分段诊刮诊断细胞级别准确率的临床因素。方法:回顾研究1993年1月至2008年1月上海交通大学医学院附属仁济医院妇产科收治的176例子宫内膜癌患者的临床资料,分析分段诊刮诊断子宫内膜癌病理分级的准确率及影响其准确率的临床因素。结果:以术后切除的子宫标本石蜡病理为标准,诊刮的病理分级总体准确率为35.2%(62/176)。50%(88/176)的患者分段诊刮细胞级别在石蜡病理结果中上升,仅14.8%(26/176)患者的肿瘤细胞分级下降。宫腔深度大于9cm,病理分级为G2或G3,浸润深度大于1/2肌层,p53阳性表达时诊刮的准确率较高。结论:分段诊刮诊断子宫内膜癌病理分级准确性较低,分化较差或进展晚期内膜癌患者的准确性较高。临床上对分段诊刮得出的肿瘤病理级别结果应谨慎。     

晚期子宫内膜癌预后相关因素分析

目的 探讨晚期子宫内膜癌预后相关因素。方法 回顾性分析我院1986年1月～1999年9月间收治的41例晚期子宫内膜癌患者临床病理资料和随访结果。结果(1)41例患者,Ⅲ期30例,其中Ⅲa期15例(36.6％),Ⅲb期3例(7.3％),ⅢC期12例(29.3％),Ⅳ期11例(26.8％)(均为Ⅳb期);子宫内膜样腺癌30例(73.2％),腺鳞癌5例(12.2%),浆乳癌5例(12.2%),透明细胞癌1例(2.4%);单纯手术2例,单纯放疗3例,单纯孕激素治疗1例,综合治疗35例;死亡17例,5年生存率35.4％。(2)Ⅲ期患者中,Ⅲa期复发3例,死亡2例,5年生存率65.6％;Ⅲb期盆腹腔复发1例(死亡),Ⅲc期复发转移8例,均死亡,5年生存率14.5％。(3)Ⅳ期患者中,盆腹腔复发3例,肺转移5例,死亡6例,3年生存率 27.7％。(4)子宫外多处癌灶22例,其中复发转移16例,死亡14例,占全部死亡的82.4％。结论 子宫内膜癌Ⅲc期预后明显差于Ⅲa期,子宫浆膜受侵、子宫外多处癌灶、宫旁组织受侵犯、宫旁淋巴管或血管有癌栓及淋巴结癌转移仍是影响Ⅲ期子宫内膜癌预后的重要因素,Ⅳ期患者易盆腹腔复发和肺转移,预后更差,晚期子宫内膜癌应进行综合治疗。     

子宫峡部内膜癌的临床病理特征及预后

目的分析子宫峡部内膜癌的临床病理特点及预后相关因素。方法对天津医科大学总医院1980年1月至2005年12月收治的349例子宫内膜癌,按肿瘤部位分为峡部内膜癌（UIE）组与非峡部内膜癌组,比较两组临床病理特征及预后。结果UIE占10.0%（35/349）。与非峡部内膜癌相比,UIE组阴道排液及腹痛的比例较高（P〈0.05）。UIE组更容易发生深肌层浸润、宫颈侵犯、脉管浸润、浆膜受累、腹腔细胞学阳性以及盆/腹腔淋巴结转移,临床分期、手术病理分期较高（P均〈0.05）,具有较低的5年生存率（P〈0.05）。多因素分析显示峡部癌灶并非是预后不良的独立性相关因素。结论子宫峡部内膜癌具有特殊的临床病理特征,其可增强其他预后不良因素的作用而影响预后。     

Peritoneal cytology as a prognostic indicator in endometrial carcinoma

Among the prognostic indicators of endometrial carcinoma, the presence of cancer cells in peritoneal washings has been suggested as indicating a poor prognosis. This proposition was examined for 373 patients; positive peritoneal washings were observed in 20 of 335 patients with stage I disease and 10 of 29 with stages II-IV. In 13 of the 30 patients there was no gross evidence of disease. Within a follow-up period of two years, positive cytology appeared to be a sign of poor prognosis.     

DNA ploidy, grade, and stage in prognosis of uterine cervical cancer

A retrospective study of 56 cases of uterine cervical squamous carcinoma evaluated DNA content, histological grade, and clinical stage as indicators of prognosis. Minimum survivor follow-up was 24 months. Following standard radiation therapy, there were 40 cures and 16 treatment failures. DNA content was measured by flow cytometry of pretreatment biopsies removed from paraffin. There were 18 diploid cases and 38 aneuploid (67.9%). Aneuploid cases included 6 with very high G2-M peaks (greater than or equal to 15% of the cell sample). DNA ploidy correlation with prognosis was not statistically significant. However, both grading by a multiple parameter method (P less than 0.0133) and staging (P less than 0.0064) were significant prognostic factors. Higher grade and stage correlated with treatment failure.     

DNA analysis,chemoresistance testing and hormone receptor levels as prognostic factors in advanced ovarian carcinoma

Summary Fifty patients with advanced (stage III or IV) ovarian carcinoma were followed-up until the date of their death or their fifth year of survival. Prognostic factors, including those currently in use, as well as ploidy and proliferation, chemoresistance testing and hormone receptor levels of the tumours were analysed for predictive value and independence from each other. In the univariate analysis, only stage, residual tumour, second-look status, chemoresistance, ploidy and proliferation were significantly correlated with survival. After being tested in a multivariate Cox regression model, however, only the results of chemoresistance testing at initiation of therapy, and second-look status at a later point, retained prognostic significance. Within the group of patients with a positive second-look, i.e., with the worst prognosis, the chemoresistance test was still able to discriminate between two subgroups with significantly different survival. Recipient of a grant from the Spanish Social Security Investigation Fund (FISS)     

The prognosis in early endometrial carcinoma. The importance of uterine papillary serous carcinoma (UPSC), age, FIGO grade and nuclear grade

278 patients with either stage I or II endometrial carcinoma treated between January 1979 and January 1982 were reviewed, particularly as regards certain prognostic factors. Uterine papillary serous carcinoma (UPSC), FIGO grade 3, nuclear grade 3, and age were the major independent prognostic factors. UPSC was diagnosed in 8% of the patients. The cancer mortality in the non-UPSC group was 7%, vs. 41% in the UPSC group. In the latter group all the deaths occurred within 2 1/2 years. Poorly differentiated non-UPSC had the same cancer death rate as UPSC, but usually had a completely different histological pattern. There was no significant difference in survival between stage I and stage II when corrected for FIGO grade and nuclear grade.     

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     

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.     

Tumor size,depth of invasion,and histologic grade as prognostic factors of lymph node involvement in endometrial cancer: A SEER analysis

Objectives

The objective of this investigation was to evaluate the risk of nodal metastasis in patients with endometrial cancer, using the Mayo criteria, in a population-based analysis.

Materials and methods

Data from the SEER registry was reviewed for endometrial cancer cases diagnosed between 1988 and 2010. Patients were considered at low-risk for nodal metastasis if their tumors were histologic grade 1 or 2, myometrial invasion was less than 50%, and tumor size equal to or less than 2 cm. Patients not meeting these criteria were considered at high-risk for nodal involvement.

Results

The final study group consisted of 19,329 women with surgically staged endometrial cancer. Of these, 1035 (5.3%) had lymph node involvement. Based on Mayo criteria, 4095 (21.1%) patients were found to be at low-risk and 15,234 (78.9%) at high-risk for nodal metastasis. Low-risk features were associated with a 1.4% risk for lymph node metastasis, compared to 6.4% in patients with high-risk features (p < 0.001). When myometrial invasion was removed from the analysis, low-risk pathologic features were associated with a 2.4% risk of lymph node metastasis, compared to 10.4% in patients with high-risk features (p < 0.001).

Conclusions

In a population-based analysis, women with low-risk endometrial cancer, as defined by the Mayo criteria, have a low rate of lymph node metastasis.     

晚期子宫内膜癌患者的治疗及预后分析

目的 探讨晚期(Ⅲ～Ⅳ期)子宫内膜癌的治疗方法及预后影响因素.方法 选择1996年1月至2006年12月间收治的晚期子宫内膜癌患者118例,对其治疗方法及预后影响因素进行回顾性分析,患者随访至2007年12月,平均随访26个月.结果 随访期内,共33例患者死亡,占28.0%;25例患者术后出现疾病进展,占21.2%.Ⅲ、Ⅳ期患者的3年总生存率分别为78.3%和39.4%,子宫内膜样腺癌和非子宫内膜样腺癌患者的3年总生存率分别为69.3%和42.0%,分别比较,差异均有统计学意义(P<0.05).4例仅有腹水细胞学检查阳性的Ⅲa期患者,术后未行辅助治疗,现已平均随访16个月均无瘤生存.单因素分析显示,手术病理分期、病理类型、肌层浸润深度、病理分级、后腹膜淋巴结切除术(包括盆腔淋巴结切除或加腹主动脉旁淋巴结切除术)和术后辅助联合放化疗与预后明显相关(P<0.05).多因素分析显示,手术病理分期和肌层浸润深度与预后明显相关(P<0.05).对不同治疗方式分析显示,行后腹膜淋巴结切除术患者的预后明显优于未行该手术者(P<0.05);术后残留灶直径≤1 cm患者的预后明显优于残留灶直径>1 cm者(P<0.05);术后行辅助联合放化疗患者的预后明显优于未行联合放化疗和仅行放疗或化疗者(P<0.05).结论 手术病理分期和肌层浸润深度是影响晚期子宫内膜癌患者预后的独立的危险因素.治疗应在满意的肿瘤细胞减灭术和后腹膜淋巴结切除术的基础上,除仪腹水细胞学检查阳性的Ⅲa期患者外,术后均应辅以联合放化疗,以改善患者的预后.     

DNA ploidy and the expression of tissue-carcinoembryonic antigen in grade III carcinoma of the breast.

A series of 50 Stage I and II, Grade III ductal carcinomas of the breast was characterized by DNA flow cytometry and further analyzed with a monoclonal antibody for carcinoembryonic antigen (CEA). The antigen was detected with the indirect immunoperoxidase technique on paraffin sections and on cytologic smears of the cell suspensions that were used for flow cytometric DNA analysis. A significant higher incidence of CEA-positivity in cytologic smears and tissue sections was found in DNA-diploid tumors (13/18 and 12/18, respectively) than in DNA-aneuploid tumors (13/22 and 12/32, respectively) (P less than 0.05 and P less than 0.025, respectively).     

Neo-angiogenesis in immunohistochemical techniques as a prognostic factor in endometrial carcinoma

OBJECTIVE: Angiogenesis in malignant tumors is a prognostic factor associated with tumor growth and metastasis. The aim of the research was: determination of the angiodensity rate in two immunohistochemical techniques, estimation of the value of the examined parameter at different stages of clinical progression and histological differentiation of endometrial carcinoma, and analysis of the obtained values as prognostic factors in the disease process. MATERIALS AND METHODS: The examination covered 86 women treated surgically for endometrial carcinoma. The preliminary histological evaluation was followed by immunohistochemical methods. The microvessels within the invasive cancer were highlighted by means of immuno-cytochemical staining to detect CD-31 and CD-105 antigen. The average value of angiodesity was estimated by means of a computer image analyser. RESULTS: The group of patients at the preinvasive stage of the disease manifested significantly statistically lower values of angiodensity. It was detected that the histological differentiation of carcinoma does not influence intensification of angiogenesis. Higher values of this parameter have an adverse influence on the survival rate. CONCLUSION: The evaluation of the angiodensity coefficient can be a helpful prognostic parameter in endometrial carcinoma.