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Background: The aim of this paper was to assess the accuracy of frozen sections histological examination and preoperative CA-125 to select patients with high risk endometrial cancer., Methods: We reviewed women with type I endometrial cancer treated from January 2011 through January 2013 at the same university hospital. Preoperative CA-125 and intraoperative frozen sections were analyzed to select patients at high risk for metastases, according to Mayo Clinic algorithm. All patients underwent hysterectomy with bilateral adnexectomy. High risk patients underwent complete surgical staging. Respectively, we compared the accuracy of CA-125, frozen sections, and an algorithm combining Ca-125 plus frozen sections, with permanent sections histology as positive control. χ2 test, Landis and Koch kappa statistics (k), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were determined for each variable., Results: One hundred seventy-two women were included. CA-125 levels, using 8.3 U/ml as cut-off value, showed 63.4% sensitivity, 51.6% specificity, 84.7% PPV, 25.0% NPV, 61.1% accuracy, and a low kappa statistics (k=0.106, P<0.125). Frozen sections demonstrated 97.3% sensitivity, 100% specificity, 100% PPV, 90.0% NPV, 97.8% accuracy and an optimal kappa statistics (k=0.934, P<0.001). The algorithm combining CA-125 with frozen sections showed 99.1% sensitivity, 48.1% specificity, 88.8% PPV, 92.9% NPV, 89.2% accuracy, and a satisfactory kappa statistics (k=0.578, P<0.001)., Conclusions: We proved the utility of Mayo algorithm even in a different institution. Combining CA-125 plus frozen sections doesn't look like advantageous compared to frozen sections alone.

Objective: The aim of this study was to investigate the frozen section (FS) accuracy in tailoring the surgical staging of patients affected by endometrial cancer, using 2 different risk classifications., Methods/materials: A retrospective analysis of 331 women affected by type I endometrial cancer and submitted to FS assessment at the time of surgery. Pathologic features were examined on the frozen and permanent sections according to both the GOG33 and the Mayo Clinic algorithms. We compared the 2 models through the determination of Landis and Koch kappa statistics, concordance rate, sensitivity, specificity, positive predictive value, and negative predictive value for each risk algorithm, to assess whether there are differences in FS accuracy depending on the model used., Results: The observed agreement between the frozen and permanent sections was respectively good (k = 0.790) for the GOG33 and optimal (k = 0.810) for the Mayo classification. Applying the GOG33 algorithm, 20 patients (6.7%) were moved to an upper risk status, and 20 (6.7%) were moved to a lower risk status on the permanent section; the concordance rate was 86.5%. With the Mayo Clinic algorithm, discordant cases between frozen and permanent sections were 19 (7.6%), and the risk of lymphatic spread was underestimated only in 1 case (0.4%); the concordance rate was 92.4%. The sensitivity, specificity, positive predictive value, and negative predictive value for the GOG33 were 92%, 94%, 92%, and 93%, whereas with the Mayo algorithm, these were 98%, 91%, 77%, and 99%, respectively., Conclusions: According to higher correlation rate and observed agreement (92.4% vs 86.5% and k = 0.810 vs 0.790, respectively), the Mayo Clinic algorithm minimizes the number of patients undertreated at the time of surgery than the GOG33 classification and can be adopted as an FS algorithm to tailor the surgical treatment of early-stage endometrial cancer even in different centers.

Objectives: A significant number of women diagnosed with atypical endometrial hyperplasia (AEH) on endometrial biopsy will be diagnosed with endometrial cancer (EC) on the hysterectomy specimen at permanent section. Surgical treatment for AEH and EC differ substantially. We have assessed the concordance in EC between frozen and permanent sections on patients undergoing hysterectomy for AEH., Materials and Methods: A retrospective review of 66 frozen sections on patients undergoing hysterectomy for AEH was performed. Frozen and permanent section diagnoses were categorized as negative or positive for malignancy. Permanent section carcinomas were classified as low or high risk based on their histopathology, myometrial invasion and differentiation. Correlation between frozen and permanent section and sensitivity, specificity, PPV, NPV and accuracy of frozen section in predicting EC in permanent section were calculated. Likelihood of diagnosing EC on frozen section was compared based on risk stratification at permanent section., Results: Frozen and permanent sections revealed malignancy in 43.9% and 56% of the patients respectively. 94.1% of high risk carcinomas were identified as EC at frozen section as compared to 55% of low risk EC. Concordance was good (κ=0.75). Sensitivity, specificity, NPV, PPV and accuracy in predicting EC at frozen section were 73%, 93.1%, 73% and 93.1% respectively. Carcinomas were detected at frozen section significantly more often if they were at high risk., Conclusions: The substantial agreement between frozen and permanent sections allows minimizing under- and overtreatment of women undergoing hysterectomy for AEH. High risk EC are efficiently identified in frozen section., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To compare the risk status for lymph nodal metastasis at frozen section in endometrial cancer by applying a model based on tumor grade and myometrial involvement., Study Design: A retrospective analysis was performed on 174 early-stage endometrial cancer patients on whom an intraoperative frozen section was requested. Patients were retrospectively divided into low, intermediate, and high risk for lymph nodal involvement based on tumor grade and myometrial invasion based on Gynecologic Oncology Group 33 data. Concordance of risk status at frozen and permanent sections was performed., Results: Risk status at frozen and permanent sections were highly correlated (P < 0.01). Agreement between frozen and permanent sections was substantial (kappa = 0.625). In 16% of the cases, frozen section underestimated the risk when compared with permanent section., Conclusion: Relying on intraoperative frozen section of the uterus to assess risk status for lymph nodal involvement in early-stage endometrial cancer patients leads to suboptimal management in a substantial number of cases.

Aim: There is no wide consensus in the literature on the clinical significance and management of symptomatic and asymptomatic polyps. Aims of the study are to evaluate frequency of premalignant and malignant histo-pathologic features in endometrial polyps resected hysteroscopically and identify clinical parameters able to predict final histopathologic diagnosis., Methods: Clinical data and pathologic report of 90 consecutive operative hysteroscopies performed on women with endometrial polyps were collected. Frequency of premalignant and malignant histopathologic features on the polyps were calculated and relation to clinical risk factors analyzed., Results: The frequency of premalignant and malignant histopathologic features in polyps was 6.7% and 2.2% respectively. Owing to the small sample size no statistical analysis to detect clinical risk factor for premalignant or malignant histopathologic features could be performed., Conclusion: Frequency of premalignant and malignant histopathologic features in symptomatic and asymptomatic patients is not negligible. Reported clinical risk factors for malignant degeneration of endometrial polypoid lesions are the same as those reported for endometrial cancer and are very common in patients with endometrial polyps. Every endometrial polyp should be resected.

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.

Objective: To evaluate interobserver reproducibility of histologic grade in endometrial adenocarcinomas of endometrioid type (EC), to assess the relationships between nuclear grade and the amount of argyrophilic nucleolar organizer region (AgNOR) proteins and to determine the prognostic value of AgNOR proteins and the main clinicopathologic parameters., Study Design: Architectural and nuclear grading were independently assessed by two pathologists in 64 formalin-fixed, paraffin-embedded surgical samples of EC obtained from an equal number of patients (age range, 38-84 years; mean, 63.5). Interobserver agreement was determined using the kappa statistic; discrepant cases were reviewed, and a consensus was reached. Standardized AgNOR analysis was performed according to the guidelines of the Committee on AgNOR Quantification, measuring the mean area of AgNORs per nucleus (NORA) by an image analysis system., Results: The kappa values for interobserver agreement were substantial for architectural grading and moderate for nuclear grading. When NORA values were compared to the nuclear grade assessed by different observers, the most significant linear correlation (r = .713, P < .001) was found for the nuclear assessment obtained by consensus of the two pathologists. Moreover, statistical analysis allowed discrimination of architectural grade 1 from grade 2 and 3 EC. By the Kaplan-Meier method, the prognosis was worse for patients with higher NORA values (> 4.212 micron 2), while, by Cox multivariate analysis, AgNOR quantity emerged as an independent prognostic variable., Conclusion: Use of standardized AgNOR analysis may be an additional and objective tool in the assessment of histologic grade as well as a reliable method of determining prognosis in EC.

Tamoxifen is a non-steroid estrogenic antagonist, used in post-surgical therapy of breast cancer. It interferes with endocrinous promotion of breast cancer. Tamoxifen could determine endometrial, even carcinomatous, alterations. The case of a postmenopausal patient surgically treated for breast cancer and successively treated with tamoxifen (20 mg/die), is reported. She underwent ultrasonographic and hysterosonographic endometrial evaluation and finally a hysterectomy with bilateral annessiectomy. This case seems to confirm tamoxifen possible carcinogenical effects on the endometrium.

Oxytocin receptors (OTRs) are expressed in endometrial cells and oxytocin (OT) participates in endometrial functions. In cancers derived from other OT target tissues, such as breast and neural tissues, the expression of OTRs and the antiproliferative effect of OT on cancer cells has been previously observed. This study was therefore designed to search for OTR expression and the OT effect in endometrial carcinomas. To demonstrate the presence and the location of OTRs and OTR mRNA immunocytochemical, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) procedures were employed in a series of human adenocarcinomas of the endometrium. Using an anti-OTR monoclonal antibody (IF3), OTRs were demonstrated in the large majority of endometrial carcinomas (82%), with a pattern of positivity varying from diffuse to focal, according to tumour differentiation. The OTR gene was demonstrated in 78% of the cases by RT-PCR and its presence was confirmed in selected cases by ISH. Moreover, in a human endometrial carcinoma cell line (COLO 684) OTR was demonstrated by immunofluorescence and RT-PCR and it was observed that OT treatment (10(-11)-10(-7) M) significantly inhibited cell proliferation. Neither toxic effects nor apoptosis were induced by OT treatment. The addition of an inhibitor of protein kinase A (PKA) to the culture medium abolished the antiproliferative effect of OT, suggesting that cAMP via PKA could be the intracellular mediator of the OT effect, as previously observed in breast and neural tumours. In conclusion, this study presents evidence of OTR expression in human endometrial carcinomas and of an OT antiproliferative effect on human endometrial cancer cells in vitro. It is further suggested that OT and OTR may be involved in the regulation of endometrial cells, not only in physiological conditions but also in a neoplastic context., (Copyright 2000 John Wiley & Sons, Ltd.)