Development and Validation of a Nomogram to Predict the Risk of Special Uterine Leiomyoma Pathological Types or Leiomyosarcoma in Postmenopausal Women: A Retrospective Study.

Purpose: The aim of this study was to investigate the risk factors of postmenopausal special uterine leiomyoma pathological types or leiomyosarcoma and to develop a nomogram for clinical risk assessment, ultimately to reduce unnecessary surgical interventions and corresponding economic expenses. Methods: A total of 707 patients with complete information were enrolled from 1 August 2012 to 1 August 2022. Univariate and multivariate logistic regression models were used to analyse the association between variables and special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. A nomogram for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients was developed and validated by bootstrap resampling. The calibration curve was used to assess the accuracy of the model and receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were compared with the clinical experience model. Results: The increasing trend after menopause, the diameter of the largest uterine fibroid, serum carcinoembryonic antigen 125 concentration, Serum neutrophil to lymphocyte ratio, and Serum phosphorus ion concentration were independent risk factors for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. We developed a user-friendly nomogram which showed good diagnostic performance (AUC=0.724). The model was consistent and the calibration curve of our cohort was close to the ideal diagonal line. DCA indicated that the model has potential value for clinical application. Furthermore, our model was superior to the previous clinical experience model in terms of ROC and DCA. Conclusion: We have developed a prediction nomogram for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. This nomogram could serve as an important warning signal and evaluation method for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients.

An integrated model for prognosis in vulvar squamous cell carcinoma.

BACKGROUND: Vulvar squamous cell carcinoma (VSCC) is a relatively rare gynecologic cancer. Unlike cervical squamous cell carcinoma (CSCC), in which nearly all cases are caused by HPV infection, most VSCCs are HPV-independent. Patients with VSCC also have worse overall survival (OS) than those with CSCC. Unlike CSCC, the risk factors of VSCC have not been extensively studied. Here, we investigated the prognostic values of clinicopathological parameters as well as biomarkers in patients with VSCC. METHODS: In total, 69 cases of VSCC accessions were selected for analysis between April 2010 and October 2020. The risk factors of VSCC were screened using Cox models to establish nomograms for predicting survival outcomes. RESULTS: Following the multivariate COX model for OS, independent predictors including advanced age (hazard ratio [HR] 5.899, p = 0.009), HPV positivity (HR 0.092, p = 0.016), high Ki-67 index (HR 7.899, p = 0.006), PD-L1-positivity (HR 4.736, p = 0.077), and CD8 + tumor-infiltrating lymphocytes (TILs) (HR 0.214, p = 0.024) were included in the nomogram for OS; multivariate COX model for progression-free survival (PFS) was used to screen prognostic factors including advanced age (HR 2.902, p = 0.058), lymph node metastasis (HR 5.038, p = 0.056), HPV positivity (HR 0.116, p = 0.011), high Ki-67 index (HR 3.680, p = 0.042), PD-L1-positivity (HR 5.311, p = 0.045), and CD8 + TILs (HR 0.236, p = 0.014) to establish the PFS nomogram model. Based on the C-index (0.754 for OS and 0.754 for PFS) from our VSCC cohort and the corrected C-index (0.699 for OS and 0.683 for PFS) from an internal validation cohort, the nomograms demonstrated good predictive and discriminative ability. Kaplan-Meier curves also supported the excellent performance of the nomograms. CONCLUSION: Our prognostic nomograms suggested that (1) shorter OS and PFS were associated with PD-L1-positivity, high Ki-67 index, and low CD8 + TILs; (2) HPV-independent tumors were associated with poorer survival outcome, and mutant p53 status showed no prognostic significance.

Endometrial Cytology in Diagnosis of Endometrial Cancer: A Systematic Review and Meta-Analysis of Diagnostic Accuracy.

BACKGROUND: Because the incidence of endometrial cancer has been increasing every year, it is important to identify an effective screening method for it. The endometrial cytology test (ECT) is considered to be the more acceptable technique compared to invasive endometrial sampling. METHODS: The study followed the Priority Reporting Project for Systematic Evaluation and Meta-Analysis (PRISMA-DTA) protocol. This systematic rating searched EMBASE and Web of Science databases for studies on ECT for endometrial cancer from the databases' dates of inception to 30 September 2022. All literature screening and data extraction were performed by two researchers, while the methodological quality of the included studies was assessed against defined inclusion criteria. And a third researcher resolves the disagreements. RESULTS: Twenty-six studies were eventually included in this final analysis. Meta-analysis results showed that the diagnostic accuracy characteristics of ECT for endometrial cancer were as follows: combined sensitivity = 0.84 [95% confidence interval (CI) (0.83-0.86)], combined specificity = 0.98 [95% CI (0.98-0.98)], combined positive likelihood ratio = 34.65 [95% CI (20.90-57.45)], combined negative likelihood ratio = 0.21 [95% CI (0.15-0.30)], and area under the summary receiver operating characteristic curve = 0.9673. CONCLUSIONS: ECT had the ability to detect endometrial cancer with strong specificity, although some studies have demonstrated significant differences in sensitivity.

Elevated expressions of SHP2 and GAB2 correlated with VEGF in eutopic and ectopic endometrium of women with ovarian endometriosis.

Aims: Protein tyrosine phosphatase Src-homology-2-domain-containing phosphatase 2 (SHP2) and adaptor protein Grb2-associated binding protein 2 (GAB2) can bind to each other in various signal transduction. However, the expression of SHP2 and GAB2 have not been investigated in endometriosis. The aim of the study was to evaluate the expressions of SHP2 and GAB2, and explore the correlation with Ki67 and VEGF in ovarian endometriosis.Materials and methods: The protein expressions and localizations were assessed immunohistochemically in ectopic, eutopic endometrium and normal endometrium from patients with (n = 30) and without (n = 30) ovarian endometriosis.Results: SHP2 was mainly present in the endometrial glandular epithelium, with increased expression in eutopic endometrium and even higher expression in ectopic endometrium compared to control endometrium (p < .05). GAB2 was immunolocalized in endometrial epithelium and stroma, increasing its expression from control endometrium to eutopic and ectopic endometrium (p < .05). Positive correlation was found between SHP2 and GAB2 in endometrium (p < .01). SHP2 and GAB2 both positively correlated with VEGF (p < .05), but not Ki67 in endometrium.Conclusions: We provide the first evidence that the protein expressions of SHP2 and GAB2 were elevated in ectopic and eutopic endometrium, suggesting GAB2-SHP2 axis regulating VEGF might contribute to the pathomechanism of endometriosis.

Roles of cell migration and invasion mediated by Twist in endometriosis.

AIM: To investigate the roles of cell migration and invasion mediated by Twist in endometriosis. METHODS: The protein levels and locations of Twist, N-cadherin and E-cadherin were measured by Western blot and immunohistochemistry in ectopic endometrium and eutopic endometrium of ovarian endometriosis as well as normal endometrium of nonendometriosis patients. The messenger RNA (mRNA) expressions of Twist, N-cadherin and E-cadherin in these tissues were measured by quantitative reverse transcription polymerase chain reaction. Stable overexpression of Twist in eutopic endometrial stromal cells was transfected with a plasmid-mediated delivery system. The protein and mRNA expressions of N-cadherin and E-cadherin were detected by western blot and reverse transcription polymerase chain reaction. The changes of migration and invasion of endometrial stromal cells were explored by transwell. RESULTS: Levels of protein and mRNA of Twist and N-cadherin showed the highest expression in ectopic endometrium of ovarian endometriosis, while lowest in normal endometrium of nonendometriosis patients. On the contrary, the expression of E-cadherin showed highest in normal endometrium of nonendometriosis patients. The overexpression of Twist after transfection significantly upregulated the protein and mRNA expression of N-cadherin, while downregulated the protein and mRNA expression of E-cadherin. There is significant difference between groups. For transwell, the overexpression of Twist in eutopic endometrial stromal cell significantly promoted cell migration and invasion. CONCLUSION: Twist might be related with the increase of migration and invasion in endometrial stromal cells, mediated by epithelial-to-mesenchymal transition.

Epithelioid trophoblastic tumor: a clinicopathological and immunohistochemical study of seven cases.

The objective of this study is to evaluate the clinicopathological features and immunohistochemical characteristics of epithelioid trophoblastic tumor (ETT). Seven cases of epithelioid trophoblastic tumor treated in the Women's Hospital of Zhejiang University from 2004 September to 2008 December were retrospectively analyzed. Immunohistochemical study was performed. The most common presenting symptom was vaginal bleeding. Four patients had prior evidence of molar pregnancy and three patients presented with metastases. Mean age at diagnosis was 34.7 years. Mean pregnancy interval was 3.39 years. Human chorionic gonadotropin levels were 33.25-174315.5 IU/l. One case died from metastasis in lungs. The remaining six patients survived without recurrence. Immunohistochemistry revealed diffusely positive for CK18, and focally positive for ß-hCG, HPL, Mel-CAM (CD146) and inhibin-alpha. Nuclear staining of Ki67 and p63 were seen. The confirmation of epithelioid trophoblastic tumor diagnosis is difficult before surgery. Surgical intervention is the recommended primary treatment.

[Clinical study of partial mole or choriocarcinoma with co-existing fetus].

OBJECTIVE: To evaluate the rare entity of partial mole or choriocarcinoma with co-existing fetus. METHODS: A total of 7 cases of partial mole or choriocarcinoma with co-existing fetus were selected to collect clinical profiles and perform auxiliary examinations such as serum ß-hCG and sonography. The data were analyzed retrospectively and all cases confirmed by surgery and histopathological diagnosis. RESULTS: There were 5 cases of partial moles with co-existing fetus. All patients stayed alive at follow-up. However, only 1 fetus delivered at 32-week gestation survived. All patients of choriocarcinoma with co-existing fetus died. Among them, 1 newborn died and another one lost follow-up after 2 years. CONCLUSION: Recently the rate of gestational trophoblastic disease with co-existing fetus is rising. It is quite important that the professionals of genetics, reproductive medicine, gynecological oncology, perinatal medicine and pathology should pay more attention to this emerging disease.

Intratumoral blood flow analysis in epithelioid trophoblastic tumors.

OBJECTIVE: The purpose of this series was to describe the transvaginal color pulsed Doppler sonographic features of epithelioid trophoblastic tumors (ETTs) and to evaluate whether there were specific sonographic criteria to accurately distinguish them from other lesions. METHODS: Seven cases of ETTs treated in the Women's Hospital of Zhejiang University were retrospectively analyzed. Doppler indices, including the Pourcelot resistive index (RI), pulsatility index (PI), and peak systolic to diastolic velocity (S/D) ratio from blood flow signals within the tumors were calculated from each waveform sample by using the software of the ultrasound machines. RESULTS: Patients with ETTs had heterogeneously echoic masses and highly abnormal flow patterns. The mean PI, RI, and S/D ratio for the patients were 0.57 (range, 0.22-1.09), 0.42 (range, 0.2-0.7), and 1.89 (range, 1.25-3.40), respectively. CONCLUSIONS: The clinical usefulness of intratumoral blood flow assessment in ETTs is yet to be established. However, the multiparameter sonographic approach can help in diagnosis of an ETT.

[Survey of gestational trophoblastic disease incidence among 3.6 million pregnancies in China].

OBJECTIVE: To survey incidence of gestational trophoblastic disease (GTD) in China and to provide useful information for prevention and better treatment of the disease. METHODS: The survey was retrospectively carried out from 1991 to 2000 and included 143 hospitals in the following seven Chinese provinces: Zhejiang, Jiangsu, Fujian, Anhui, Jiangxi, Shanxi and Henan. RESULTS: Excluding incomplete data, data from 118 hospitals from seven provinces were finally analyzed. The total numbers of pregnancy and GTD were 3,674, 654 and 14,222, respectively. The GTD cases occurred mainly among 20 - 34 year old women, which accounted for 85.5% of total GTD. The incidence of GTD was 3.87 per thousand. There were 9,194 cases (64.6%) of hydatidiform, 3,452 cases (24.3%) of invasive mole, 1521 cases (10.7%) of choriocarcinoma, 55 cases (0.4%) of placenta-site trophoblastic tumor, respectively. CONCLUSIONS: The results of this survey are reliable and representative due to large sampling and hospital-based data collection. The incidences of GTD decreased significantly compared with 1950s'. It is important to take pathological examination for GTD and to diagnose complate mole and partial mole correctly.

[Inhibitory effect of tumor suppressor PTEN on cell growth of endometrial carcinoma].

OBJECTIVE: To evaluate the inhibitory effect of tumor suppressor PTEN on cell growth of endometrial carcinoma. METHODS: The exogenous wild PTEN cDNA via an adenoviral vector (Ad-PTEN) was introduced into Ishikawa cells. The expression of PTEN protein was detected by Western blot. The growth of Ishikawa cells was evaluated by trypan blue exclusion method and MTT. RESULTS: The expression of PTEN protein was induced on day 1, and greatly increasing on day 3 - 5 after Ad-PTEN infection. The expression of PTEN significantly inhibited the growth of Ishikawa cells, and also significantly inhibited the growth of Ishikawa cells induced by IGF-II. CONCLUSION: Adenovirus-mediated introduction of exogenous PTEN into human endometrial carcinoma cells can induce growth suppression. PTEN gene may be a novel therapeutic agent for endometrial carcinoma.

[Changes in gene expression profiles of hydatidiform mole and choriocarcinoma as compared with trophoblast hyperplasia].

OBJECTIVE: To study the relationship of changes in gene expression profiles of hydatidiform mole and choriocarcinoma with hyperplasia of trophoblasts. METHODS: The differentially expressed genes were analyzed in two pairs of tissues of hydatidiform mole versus normal villi, and in two pairs of normal primary culture trophoblasts versus JAR cell line of chariocarcinoma, using cDNA microarray containing 4096 genes. To confirm the results of cDNA microarray analysis, expressions of some up-regulated genes related to DNA synthesis in normal villi, hydatidiform mole, and 2 choriocarcinoma cell lines (JAR and JEG-3) were examined by immunohistochemistry, immunoblotting and RT-PCR. RESULTS: A total of 89 genes were differentially expressed in all hydatidiform moles, accounting for 2.2% of the genes arrayed. Of the 89 genes, 24 were up-regulated and 65 were down-regulated. Compared with normal primary trophoblasts, there were 433 genes up-regulated and 380 genes down-regulated in JAR cell line. Forty six genes were up-regulated in both hydatidiform mole and choriocarcinoma, while 13 genes were down-regulated. Some genes associated with cell proliferative inhibition were significantly down-regulated, whereas those associated with cell proliferation, malignant transformation, metastasis and drug resistance were highly up-regulated. The expressions of thymidine kinase 1, the small subunit of ribonucleotide reductase (RRM2) were significantly increased in hydatidiform mole, JAR and JEG-3 cells. CONCLUSION: Abnormal expression of genes exists in hydatidiform mole and choriocarcinoma. Hyperplasia of trophoblasts may be related to over-expression of genes coding for synthetic enzymes.

[Preliminary study on gene expression profile of endometrial adenocarcinoma].

OBJECTIVE: To determine candidate genes of endometrial adenocarcinoma. METHODS: To compare the gene expression profile in 2 endometrial adenocarcinoma tissues and 2 normal endometria by HGEC-40s GeneChip probe including 4096 genes array. Expression differences between normal and malignant tissue groups were measured by GenePixPro3.0 software. RESULTS: 350 genes with a ratio below 0.5 and above 2.0 showed discrimination between normal and malignant groups. Thirty three genes with ratio above 3 were up-regulated, forty-four genes with ratio below 0.3 were down-regulated. CONCLUSION: The overexpression of oncogenes with their disturbed or constitutively activated signal transduction cascades alone or in combination with the mutation-induced silencing of tumor suppressor genes is associated with malignant transformation.

[Study of DNA microarray chip of associated genes of hydatidiform mole].

OBJECTIVE: To screen genes which may associate with the development and malignant transformation of hydatidiform mole. METHOD: The differentially expressed genes were analyzed between the tissues of two cases of hydatidiform mole and the normal placental tissues of two cases of pregnancy which had almost the same pregnant ages as hydatidiform mole, using cDNA chips containing 4,096 genes. RESULTS: There were total 89 genes significantly differently expressed in all hydatidiform moles, counting for 2.2% of total genes. Compared with normal villi, 24 genes in hydatidiform mole were up-regulated and 65 genes were down-regulated. Bioinformatical analysis of genes showed genes associated with cell proliferative inhibition, such as Ras GTPase activating protein, TGF-beta IIR alpha, BTG2 were significantly down-regulated, whereas genes associated with cell proliferation, malignant transformation and tumor metastasis as thymidine kinase, ribonucleotide reductase, glucose transport protein were highly up-regulated. CONCLUSION: cDNA chip technique is one kind of very effective methods in screening associated genes in hydatidiform mole.