A study evaluating liquid-based endometrial cytology test and transvaginal ultrasonography as a screening tool for endometrial cancer in 570 postmenopausal women.

OBJECTIVE: To evaluate the combination of transvaginal ultrasonography (TVS) and endometrial cytology test (ECT) as a potential diagnostic strategy for endometrial cancer and endometrial precancerous lesions in postmenopausal patients. METHODS: 570 postmenopausal patients admitted in our hospital due to abnormal bleeding or other symptoms and/or with endometrium thickness over 5 mm on ultrasound. The endometrial thickness was evaluated by TVS. Following obtainment with written consent, all patients underwent ECT, hysteroscopy and then dilatation and curettage (D&C). Cytological sampling was conducted by scratching the uterus cavity using SAP-1 and the samples were prepared as liquid-based smear using SurePath technology. The samples were stained using Papanicolaou method. The correlation between cytological diagnosis and TVS results with the D&C histological diagnosis was analyzed. The WHO classification was used for diagnosis. RESULTS: Sensitivity of ECT, TVS, ECT or TVS positive, ECT and TVS positive to diagnose atypical hyperplasia or worse were estimated at 80.7%, 86.8%, 97.4%, 70.2%, specificity at 94.7%, 20.4%, 17.5%, 88.4%, positive predictive value at 58.2%, 21.1%, 22.8%, 60.2%, negative predictive value at 94.4%, 86.1%, 96.4%, 92.2%, and accuracy at 84.6%, 33.7%, 33.5%, 84.7%, respectively. CONCLUSIONS: Transvaginal ultrasonography and Endometrial cytology test may be regarded as a effective first-line method in endometrial pathology detection in postmenopausal women.

Clinical characteristics and prognostic characterization of endometrial carcinoma: a comparative analysis of molecular typing protocols.

BACKGROUND: Endometrial carcinoma (EC) is one of the most common gynecological malignancies in China and globally, accounting for the fourth-prevalent cancer in women. Although numerous studies have confirmed prognostic value of The Cancer Genome Atlas (TCGA) molecular subgroups, it is unclear how they are combined with histological features. The main objective of this study was to compare ProMisE and TCGA classification for the rapid and accurate prediction of prognosis within EC patients, together with the provision of a revised strategy for individualized diagnosis and treatment of patients. METHODS: Within this study, 70 patients with EC from Beijing Tsinghua Changgeng Hospital (affiliated to Tsinghua University) were retrospectively examined between July 2015 and December 2021. Samples were processed for determination of clinical markers, together with ProMisE and TCGA classification. RESULTS: Comparative analysis across four TCGA types (POLE, Low-CN, High-CN, and MSI-H) and age, was statistically significant (χ²= 7.000, p = 0.029). There was no significant difference observed among the four TCGA types and FIGO stage, vascular invasion and depth of invasion, or lymph node metastasis and tumor area. There was no significant association between the expression of Vimentin, Ki-67, PTEN, MSH2, PAX-8, ß-catenin, CD10, ER, PR, P16, MLH1, and PMS2 with the four TCGA types. In addition, p63 expression (χ²= 11.09, p = 0.029) and p53 expression (χ²= 11.585, p = 0.005) were statistically significant. Numerous models demonstrated that patients with POLE mutations and low-CN had higher progression free survival (PFS) and overall survival (OS), whereas those with high-CN had lowest values. The log-rank test revealed that the survival rate of PR-positive and ER-positive patients was significantly higher (p < 0.001). CONCLUSION: Overall, these results can be of additional benefit for clinical applications, in comparison to the ProMisE classification method. In addition, PR, ER, vascular infiltration, hyperlipidemia and atherosclerosis were found to be the key factors affecting EC prognosis.

[Correlations of p-AKT with PTEN, P53, HER-2 expressions in endometrial carcinoma and their relationship with patient survival].

OBJECTIVE: To investigate the correlation of phosphorylated protein kinase B(p-AKT) with phosphatase and tensin homolog(PTEN), P53,human epidermal growth factor receptor 2(HER-2) expressions in endometrial carcinoma and their significance. METHODS: The expressions of p-AKT with PTEN, HER-2, P53 and Ki67 were assessed in 95 endometrial carcinomas using immunohistochemistry. The biomarker expressions correlated with clinicopathologic variables and with patient survival. RESULTS: (1) p-AKT was positive in 53.7% (51/95) of tumors and was found to express almost similarly in endometrioid adenocarcinoma(EC) and non-enometrioid adenocarcinoma (NEC). There was no significant difference of patient survival between p-AKT positive and negative subgroups (P=0.757). (2) PTEN loss was found in 56.8%(54/95) of tumors, and occurred more often in EC(60.7%, 51/84) than in NEC (27.3%, 3/11), which was of statistical significance (P=0.035). The patients with PTEN loss had a longer survival than those without (P=0.015). (3) Although there was no significant correlation between p-AKT and PTEN expression, the extended analysis showed that the predictive value of PTEN loss in p-AKT positive subgroup (P=0.148) was lower than that in p-AKT negative expression subgroup (P=0.055). Meanwhile p-AKT positive and PTEN loss might have synergic effect on tumor proliferation, Ki67 positive rate was highest in PTEN+/p-AKT+ subgroup (40.0%) and lowest in PTEN-/p-AKT- subgroup (8.7%), which was of significant difference (P=0.015). (4) No correlation was found between p-AKT expression and P53 or HER-2 status (P>0.05). On the other hand, HER-2 and P53 positive correlated significantly (r=0.209, P=0.041) and occurred more frequently in NEC (45.5%, 100.0%) than in EC(6.0%, 42.9%)(P <0.05), which were found to predict poor survival (P<0.05). CONCLUSION: p-AKT was activated equally in EC and NEC. p-AKT positive alone might have limited effect on patient survival, however, p-AKT expression might lower the predictive value of PTEN loss in endometrial carcinoma. Moreover, p-AKT positive and PTEN loss might have synergic effect on tumor proliferation. On the other hand, as p-AKT expression did not have any correlations with PTEN, P53 and HER-2 status in this cohort, there might be other important factors involved in p-AKT activation in endometrial carcinoma. In sum, further investigation should be conducted in the targeted therapy based on p-AKT and associated molecular mechanism in advanced endometrial carcinoma.

[Significance of phosphoinositide 3 kinase/AKT pathway alterations in endometrial carcinoma].

OBJECTIVE: To investigate the clinicopathologic and prognostic implications of phosphoinositide 3 kinase (PI3K)/AKT pathway alterations in endometrial cancers of Chinese women. METHODS: The expression of PTEN, p-AKT, and ER/PR was assessed in 71 cases of endometrial carcinoma by immunohistochemistry (EnVision method). The PIK3CA mutation at exon 9 and exon 20 was analyzed by PCR and direct sequencing in 34 tumors. RESULTS: (1) Of the 71 cases of endometrial carcinoma, 65 cases were endometrioid adenocarcinoma (EEC) and 6 cases were nonendometrioid adenocarcinoma (NEEC). PTEN loss of expression was found in 63.4% (45/71) of tumors, and more commonly occurred in EEC (66.2%, 43/65) than that in NEEC (2/6, P = 0.18). Patients with PTEN loss in their tumors (45 cases) had a better survival than those without (26 cases, P = 0.07). In ER negative subgroup, the patients with PTEN loss of expression (12 cases) had longer survival than those with normal PTEN expression (7 cases; P = 0.04). (2) The frequency of PIK3CA mutation was 41.2% (14/34) with a hot mutation spot at T544 in exon 9. PIK3CA mutations more commonly occurred in EEC (44.8%, 13/29) than in NEEC (1/5, P > 0.05). The mutations at exon 9 more commonly occurred in EEC, well- and moderately-differentiated EEC, and tumors at early stage (P > 0.05). On the contrary, in tumors at early stages, the frequency of mutations in exon 20 (14.3%, 4/28) was significantly lower than that at late stages (4/6, P = 0.01). (3) p-AKT was positive in 59.2% (42/71) of tumors that were more frequently found in EEC (60.0%, 39/65) than that in NEEC (3/6, P = 0.68). However, the significant difference of p-AKT expression was found between well- and moderately-differentiated EEC (75.0%, 21/28; 53.6%, 15/28) and poorly-differentiated EEC (3/9, P = 0.02). Moreover, p-AKT expression was significantly correlated with positive ER (r = 0.339, P = 0.00). CONCLUSIONS: Endometrial carcinoma patients with loss of PTEN and p-AKT positivity have a favorable prognosis. PIK3CA mutations at exon 9 or 20 may have different impact on the prognosis. The function of PTEN loss and p-AKT expression may vary according to different hormone status.