Progress of brain metastasis in common gynecologic malignancies / 肿瘤研究与临床

Brain metastasis is an uncommon complication that occurs in the advanced stage of gynecologic malignancies. Brain metastasis tends to be one of the major factors contributing to the poor prognosis of patients. There have been more reports about brain metastasis in cervical, ovarian and endometrial cancers in recent years due to the growth of large databases and improved diagnostic methods. Great attention has been paid to the selection of appropriate therapeutic options to improve the survival of gynecologic malignancies patients with brain metastasis. This article reviews the research progress of brain metastasis in cervical, ovarian and endometrial cancers, aiming to provide better options for treatment of patients with common advanced gynecologic malignancies.

Combined synthetic MRI and multiplexed sensitivity encoding diffusion weighted imaging(MUSE-DWI)for differentiating benign and malignant endometrial lesions / 中国介入影像与治疗学

Objective To observe the value of combined synthetic MRI and multiplexed sensitivity encoding diffusion weighted imaging(MUSE-DWI)for differentiating benign and malignant endometrial lesions.Methods Data of 112 patients with benign or malignant endometrial lesion confirmed by pathology were retrospectively analyzed.According to pathologic diagnosis,the patients were divided into malignant group(n=72)and benign group(n=40).Synthetic MRI and MUSE-DWI quantitative parameters,including T1,T2,proton density(PD)and apparent diffusion coefficient(ADC)of all lesions were acquired.The clinical data as well as ADC,T1,T2 and PD values of lesions were compared between groups,and those being significantly different between groups were included in univariate and multivariate logistic regression.Then the univariate and combined models were established for differentiating benign and malignant endometrial lesions.The receiver operating characteristic curves were drawn,and areas under the curves(AUC)were calculated to evaluated the diagnostic efficacy of the models,which were compared with DeLong test.Results Patients'age in malignant group were higher than that in benign group(P＜0.05).The length of the maximum diameter was larger,ADC,T2 and PD values were lower in malignant lesions than those in benign ones(all P＜0.05),while no significant difference of T1 value was found between groups(P=0.074).The AUC of ADC univariate model was 0.966,and there was no significant difference in AUC(0.970)between the combined ADC+T2+PD model(adjusted P＞0.05),but both higher than AUC of T2 univariate model(0.618),PD univariate model(0.664)and the combined T2+PD model(0.668)(all adjusted P＜0.05).Conclusion ADC univariate model and combined model with other parameters of combined synthetic MRI and MUSE-DWI could be used to effectively differentiate benign and malignant endometrial lesions.

Association of insulin-like growth factor II mrna-binding protein 3 (IMP3) expression with prognostic and morphological factors in endometrial cancer

Abstract Objective Endometrial cancer (EC) is a heterogeneous disease with recurrence rates ranging from 15 to 20%. The discrimination of cases with a worse prognosis aims, in part, to reduce the length of surgical staging in cases with a better prognosis. This study aimed to evaluate the association between Insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression and prognostic and morphological factors in EC. Methods This retrospective, cross-sectional, analytical study included 79 EC patients - 70 endometrioid carcinoma (EEC) and 9 serous carcinoma (SC) - and 74 benign endometrium controls. IMP3 expression was evaluated by immunohistochemistry-based TMA (Tissue Microarray), and the results were associated with morphological and prognostic factors, including claudins 3 and 4, estrogen and progesterone receptors, TP53, and KI67. Results IMP3 expression was significantly higher in SC compared to EEC in both extent (p<0.001) and intensity (p=0.044). It was also significantly associated with worse prognostic factors, including degree of differentiation (p=0.024, p<0.001), staging (p<0.001; p<0.001) and metastasis (p=0.002; p<0.001). IMP3 expression was also significant in extent (p=0.002) in endometrial tumors compared with controls. In addition, protein TP53 and KI67 showed significant associations in extent and intensity, respectively. Conclusion IMP3 expression was associated with worse prognostic factors studied. These findings suggest that IMP3 may be a potential biomarker for EC poorer prognosis.

Netrina-1 en sangre como biomarcador para la detección del cáncer de endometrio / Serum Netrin-1 as a biomarker for Endometrium Cancer detection

RESUMEN Investigar la relación de la netrina-1 preoperatoria con factores clinicopatológicos y pronósticos importantes y los niveles de corte adecuados en pacientes con cáncer de endometrio. En este estudio prospectivo y observacional, el grupo de casos y el de controles se seleccionaron entre las pacientes que acudieron a la Clínica de Oncología Ginecológica. Se extrajeron 4 mL de sangre venosa en un tubo de bioquímica de cada paciente durante el período preoperatorio. Los valores de netrina para predecir la presencia de malignidad se analizaron mediante el análisis de la curva ROC (receiver operating characteristics). El valor de corte se calculó según el índice de Youden. En el estudio, el valor de corte de malignidad según el nivel de netrina fue determinado en 645,50 mg/dL en el análisis ROC (utilizando el índice de Youden). La probabilidad de malignidad en individuos con valores de netrina superiores a este punto de corte fue del 78,2% (IC 95%: 0,680 a 0,884). La sensibilidad de la netrina para mostrar la probabilidad de malignidad en este valor de corte fue del 87,5% y la especificidad del 63,6%. La netrina-1 puede ser un biomarcador potencial para la detección del cáncer de endometrio y la evaluación de su pronóstico.

ABSTRACT To investigate the relationship of preoperative netrin-1 with important clinicopathological and prognostic factors and appropriate cut-off levels in patients with endometrial cancer. In this prospective, observational study, the case and control group were selected among patients who applied to the Gynecological Oncology Clinic. Four mL of venous blood was drawn into a biochemistry tube from each patient during the preoperative period. Netrin values in predicting the presence of malignity were analyzed using ROC (receiver operating characteristics) curve analysis. The cut-off value was calculated according to the Youden index. In the study, the cut-off value of malignancy according to the netrin level was determined as 645.50 mg/dL in the ROC analysis (using the Youden index). The probability of malignancy in individuals with Netrin values above this cut-off was 78.2% (95% CI 0.680-0.884). The sensitivity of netrin in showing the probability of malignancy at this cut-off value was 87.5%, and the specificity 63.6%. Netrin-1 can be a potential biomarker for endometrial cancer detection and prognosis evaluation.

Tumor de colisión de útero. Reporte de caso y revisión de la literatura / Uterine collision tumor. Case report and review of he literature

Objetivos: Reportar el caso de una paciente con tumor de colisión del útero y realizar una revisión de la literatura respecto al diagnóstico histopatológico, tratamiento y pronóstico de esta condición. Materiales y métodos: Mujer de 76 años que consultó al centro nacional de referencia del cáncer en Bogotá (Colombia), donde se hizo el diagnóstico de tumor de colisión del útero, compuesto por un adenocarcinoma de endometrio tipo seroso y adenosarcoma de cérvix. Recibió tratamiento quirúrgico más quimioterapia y radioterapia complementaria, falleció a los 16 meses. Se realizó una búsqueda de la literatura en las bases de datos Medline vía PubMed y Embase, que incluía reportes y series de caso de mujeres con diagnóstico de tumor de colisión del útero, y se extrajo información sobre el diagnóstico, tratamiento y pronóstico. Se realizó un resumen narrativo de los hallazgos. Resultados: La búsqueda identificó 36 títulos, de los cuales se incluyeron 14 estudios que incluían 17 pacientes. El diagnóstico histopatológico más frecuente fue el adenocarcinoma endometrioide de endometrio y sarcoma endometrial de alto y bajo grado (47 %). El tratamiento básico fue quirúrgico. Cerca del 50 % recibió tratamiento adyuvante con quimioterapia y radioterapia (15 %). La sobrevida a un año fue del 75 %. Conclusiones: En la literatura no se identificaron casos de tumores de colisión de útero con la histopatología y en la ubicación del caso presentado. La mortalidad a dos años es cercana al 28 % si se toma en cuenta el caso reportado. Se necesitan más estudios que describan la inmunohistoquímica, el tratamiento y el pronóstico de esta condición.

Objectives: To report the case of a patient with a uterine collision tumor and to conduct a review of the literature. Material and methods: A 76-year-old patient who presented to the national cancer referral center in Bogota (Colombia), where she was diagnosed with a uterine collision tumor consisting of a serous-type endometrial adenocarcinoma and a cervical adenosarcoma. The patient underwent surgical treatment followed by chemotherapy and supplemental radiotherapy, and died 16 months later. A search was conducted in the Medline via PubMed and Embase databases, including reports and case series of women with a diagnosis of uterine collision tumor, with retrieval of information regarding diagnosis, treatment and prognosis. A narrative summary of the findings was made. Results: The search identified 36 titles, of which 14 studies with 17 patients were included. The most frequent histopathological diagnosis was endometrial adenocarcinoma and high and low grade endometrial sarcoma (47 %). Primary treatment was surgery and adjuvant treatment with chemotherapy and radiotherapy (15 %) was performed in close to 50 % of cases. One-year survival was 75 %. Conclusions: No cases of uterine collision tumors with the histopathology or in the location of the reported case were found in the literature. If this reported case is taken into account, 2-year mortality is 28 %. Further studies to describe the immunohistochemistry, treatment and prognosis of this condition are needed.

Analysis of clinicopathologic features of false negative sentinel lymph nodes in patients with endometrial cancer / 国际肿瘤学杂志

Objective:To compare the clinicopathological features of patients with false negative and true negative pathological biopsy of sentinel lymph nodes in endometrial cancer, and to explore the related factors of missed diagnosis of sentinel lymph nodes.Methods:From January 2020 to January 2022, 31 patients underwent sentinel lymph node biopsy combined with systematic lymph node resection in the First Affiliated Hospital of Shandong First Medical University were retrospectively analyzed, of which 2 were false negative and 29 were true negative. PubMed literature on sentinel lymph node false negative of endometrial cancer was searched from the establishment of the database to December 2022, with the search terms "Sentinel lymph node" "Endometrial neoplasms" and "False negative" . A total of 15 cases of false negative patients with similar methods to this study were extracted. In the false negative group, there were 17 false negative patients with sentinel lymph node negative but systemically excised lymph node positive, including 2 cases in our hospital and 15 cases in the literature. The true negative group included 29 true negative patients with negative sentinel and systemic lymph nodes, all from our hospital. The clinicopathologic features of the two groups were compared.Results:There were statistically significant differences in tumor grade ( χ2=6.09, P=0.014) , lymph vascular space invasion ( P=0.012) and myometrial invasion ( χ2=9.66, P=0.002) between the two groups. However, there was no significant difference in histological type between the two groups ( χ2=0.19, P=0.661) . Conclusion:There is a risk of false negative for sentinel lymph node biopsy in patients with endometrial carcinoma with high-grade tumor, myometrial invasion ≥1/2 and lymph vascular space invasion.

Expression of serum connective tissue growth factor, glyoxalase Ⅰ, pyruvate kinase M2 in endometrial carcinoma and its relationship with clinicopathological features / 中国医师进修杂志

Objective:To explore the expression of serum connective tissue growth factor (CTGF), glyoxalase Ⅰ (GLO-I) and pyruvate kinase M2 (PKM2) in endometrial cancer and their relationship with clinicopathological characteristics.Methods:A total of 96 endometrial cancer patients in Yuechi County People's Hospital from February 2015 to February 2017 were selected as the research group, 48 patients with endometrial hyperplasia during the same period were selected as the benign control group, and 48 patients with healthy physical examination during the same period were selected as the healthy control group. The serum levels of CTGF, GLO-Ⅰ, and PKM2 in the three groups were analyzed. The correlation between serum levels of CTGF, GLO-Ⅰ and PKM2 in the research group was analyzed, and the relationship between each serum index and clinicopathological characteristics was analyzed.Results:The levels of serum CTGF, GLO-Ⅰ and PKM2 in the research group were higher than those in the benign control group and healthy control group: (184.31 ± 37.14) μg/L vs. (110.45 ± 20.59), (17.28 ± 0.42) μg/L; (95.17 ± 16.56) pmol/L vs. (56.29 ± 10.14), (9.08 ± 0.66) pmol/L; (20.25 ± 6.13) μg/L vs. (13.11 ± 4.58), (9.05 ± 2.74) μg/L; and the levels of serum CTGF, GLO-Ⅰ and PKM2 in the benign control group were higher than those in the healthy control group, there were statistical differences ( P<0.05). The results of Pearson correlation analysis showed that the level of CTGF had positive correlation with GLO-Ⅰ and PKM2 ( r = 0.713, 0.741, P<0.05), and the level of GLO-Ⅰ had positive correlation with PKM2 ( r = 0.823, P<0.05). The results of Spearman correlation analysis showed that the levels of CTGF, GLO-Ⅰ, PKM2 had positive correlation with FIGO stage ( r = 0.609, 0.704, 0.721; P<0.05), myometrial invasion depth ( r = 0.753, 0.695, 0.719; P<0.05), lymph node metastasis ( r = 0.776, 0.744, 0.640; P<0.05); had negative correlation with the degree of differentiation ( r = - 0.711, - 0.720, - 0.668; P<0.05). Conclusions:Serum CTGF, GLO-I, PKM2 expression levels are abnormally elevated in patients with endometrial cancer, which are significantly related to multiple clinicopathological characteristics.

Expression of acetaldehyde dehydrogenase 2 in endometrial carcinoma and its correlation with clinical characteristics of patients / 中国医师杂志

Objective:To detect the expression of acetaldehyde dehydrogenase (ALDH) 2 and microRNA (miR)-135b-3p in endometrial cancer (EC) tissues, and to explore their correlation with clinical characteristics.Methods:94 endometrial cancer tissue specimens (EC group) and 60 normal endometrial specimens (control group) were selected from Northwest Women′s and Children′s Hospital from February 2019 to February 2022. Real time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression changes of ALDH2 mRNA and miR-135b-3p in endometrial tissue of two groups, and immunohistochemistry was used to detect the positive expression rate of ALDH2 protein. The relationship between the expression levels of ALDH2 and miR-135b-3p and the clinicopathological characteristics was analyzed.Results:The expression of ALDH2 mRNA in the EC group (0.67±0.15) was lower than that in the control group (1.05±0.12), and the expression level of miR-135b-3p (1.52±0.26) was higher than that in the control group (1.01±0.06). The positive expression rate of ALDH2 in cancer tissue of EC group was 30.85%(29/94), which was lower than 51.67%(31/60) in normal endometrial tissue of the control group ( P<0.05). The expression levels of ALDH2 mRNA and miR-135b-3p in EC patients were related to International Federation of Obstetrics and Gynecology (FIGO) stage, lymph node metastasis, differentiation and myometrium invasion (all P<0.05), but not to age, pathological type, menopause, HPV infection, menarche age, parity, tumor length and BMI (all P>0.05). Conclusions:In EC tissues, the expression of ALDH2 is down-regulated and the expression of miR-135b-3p is up-regulated, which may be involved in the occurrence and development of EC.

Challenges in screening and early detection of gynecologic malignancies / 中国医师杂志

The cancer burden caused by gynecological malignancies poses a serious threat to the health of women in China. Screening and early diagnosis are the key means to reduce the incidence rate and mortality of cancer. This article aims to briefly summarize the current status and challenges of screening and early diagnosis of three common female reproductive tract malignancies (cervical cancer, endometrial cancer, and ovarian cancer), in order to clarify the current stage and future direction of efforts.

Research on the average age of onset of endometrial cancer based on data mining / 中国医师杂志

Objective:To explore the average age at onset of endometrial cancer (EC) and the differences between domestic and international factors.Methods:Pubmed, Wanfang Database, VIP Information Resource System, and China National Knowledge Infrastructure (CNKI) were selected to extract clinical research data related to EC. Through data mining methods such as frequency analysis and cluster analysis, we compared the differences in the average age of onset of EC between domestic and foreign countries.Results:A total of 280 articles that met the inclusion criteria were selected, and frequency analysis found that the average age of onset of EC in the Chinese population was mostly concentrated under 57 years old, while in European and American countries, it was mainly concentrated above 57 years old. Through cluster analysis, it was found that the average age of onset in China was clustered in one category with most Asian countries, while European and American countries and Australian countries were clustered in another category. Through analysis of domestic and foreign articles, it was found that the average age of onset of EC did not show a significant upward or downward trend with years.Conclusions:There are differences in the average onset age of EC among different countries and regions. The onset age of EC in Asian populations is significantly earlier than that in European and American populations. The average onset age of EC in Chinese populations is 54 years old, and there is no trend towards a younger onset of EC.

Analysis of risk factors for endometrial atypical hyperplasia and endometrial cancer / 中国医师杂志

Objective:To explore the high-risk factors of endometrial cancer (EC) and provide clinical basis for early screening, diagnosis and treatment of EC.Methods:From January 2017 to December 2022, patients admitted to Shanxi Provincial Maternal and Child Health Hospital for hysteroscopic surgery or diagnostic curettage due to abnormal uterine bleeding, postmenopausal vaginal bleeding and other related symptoms were selected as the research objects. After histopathological examination, they were diagnosed with no atypical endometrial hyperplasia (EH), atypical endometrial hyperplasia (AEH), and EC as the research subjects. The general data of patients′ records, vaginal ultrasound, cervical liquid-based cytology test (LCT), carbohydrate antigen 125 (CA125) and pelvic magnetic resonance imaging were collected, and a case-control study was conducted and the risk factors of AEH and EC were explored using univariate and multivariate logistic regression analysis.Results:This study included a total of 420 cases, including 215 in the EH group, 69 in the AEH group, and 136 in the EC group. Through the comparison of various indicators among the three groups and the results of univariate factor logistic regression analysis, age, menopause, previous delivery history, hypertension, diabetes, color ultrasound showed endometrial thickening (>10 mm), uneven endometrial echo, abnormal echo mass in the uterine cavity, endometrial blood flow signals, cervical LCT examination showed that atypical glandular cells were related to the occurrence of EC, with a statistically significant difference (all P<0.05). The results of multivariate logistic regression analysis showed that age>48 years ( OR=3.65, 95% CI: 2.06-6.45), menopause ( OR=3.19, 95% CI: 1.46-6.98), uneven endometrial echo ( OR=4.08, 95% CI: 2.26-7.36), and intrauterine blood flow signal ( OR=2.91, 95% CI: 1.52-5.58), cervical LCT suggests that atypical glandular cells ( OR=4.25, 95% CI: 1.38-13.11) were independent risk factors for EC and precancerous lesions (all P<0.05). Conclusions:For patients with clinical symptoms such as abnormal uterine bleeding or postmenopausal bleeding, timely and focused screening based on whether they have EC risk factors is an economic, safe, and effective method for early detection and treatment of EC.

Clinical characteristics of elderly patients with Lynch syndrome-associated endometrial cancer and analysis of MSH2 gene variation in their families / 中华老年医学杂志

Objective:To study the clinical characteristics of Lynch syndrome-associated endometrial cancer in elderly patients and the relationship of the disease with MSH2 gene mutations in patients' families.Methods:Clinical data of 473 elderly patients with endometrial cancer admitted to our hospital between January 2016 and January 2021 were retrospectively analyzed.MSH2 gene mutations were detected and verified by DNA sequence analysis, real-time quantitative PCR and reverse transcription PCR.Patients were divided into a Lynch syndrome group and a non-Lynch syndrome group, and the clinicopathological features of the two groups were compared.Results:Of 473 endometrial carcinoma patients, 46(9.7%)had embryogenic mutations of the MMR gene and were diagnosed with Lynch syndrome, with 18, 6, 24 and 10 patients carrying MLH1, PMS2, MSH2 and MSH6 mutations, respectively.There were 3 mutations in the MSH2 gene, including exon 7 1380C>A, exon 12 2011A>G and exon 13 2756A→AC.The proportions of patients with G3 grade endometrioid adenocarcinoma, lower uterine segment involvement and a history of Lynch syndrome-associated malignant tumors in the Lynch syndrome group were significantly higher than those in the non-Lynch syndrome group( χ2=8.935, 8.303, 9.770, all P<0.05). Conclusions:Poorly differentiated endometrioid adenocarcinoma, predisposition to lower uterine segment involvement and familial inheritance are the main clinical manifestations of Lynch syndrome-associated endometrial carcinoma in elderly patients, with the most common mutations seen in the MSH2 gene.

Efficacy of the enhanced recovery after surgery approach in endometrial cancer patients treated with surgical staging and its influence on the oxidative stress response / 中华老年医学杂志

Objective:To analyze the efficacy of the enhanced recovery after surgery(ERAS)approach in endometrial cancer patients treated with surgical staging and its beneficial effects on the oxidative stress response.Methods:Eight-two endometrial cancer patients treated with surgical staging at our hospital between March 2020 and March 2022 were recruited and divided into different groups using a computer-generated random number table, with 41 in the control group who were given routine intervention and 41 in the observation group receiving ERAS.Results:About perioperative performances, the oxidative stress response, inflammatory factor levels and complications were compared between the two groups.Results in the observation group, the intraoperative body surface temperature was higher than in the control group[(36.71±0.22)℃ vs.(36.20±0.21)℃, t=10.737, P=0.000], and the time from the end of surgery to first water intake[(4.41±1.30)h vs.(6.79±1.28)h, t=8.353, P=0.000], to first food intake[(7.86±1.35)h vs.(12.88±2.57)h, t=11.073, P=0.000], to first ambulation[(12.92±3.11)h vs.(24.24±5.06)h, t=12.204, P=0.000], to first flatus[(24.11±4.96)h vs.(35.13±6.20)h, t=8.887, P=0.000], to first bowel movement[(2.67±0.63)d vs.(4.03±1.15)d, t=6.641, P=0.000]and the length of hospitalization[(3.31±1.25)d vs.(5.77±1.59)d, t=7.788, P=0.000]were shorter than in the control group.On the third day after surgery, the levels of malondialdehyde[(77.96±7.62)μmol/L vs.(90.16±7.88)μmol/L, t=7.126, P=0.000], advanced oxidation protein products[(33.16±4.75)μmol/L vs.(43.55±5.37)μmol/L, t=9.280, P=0.000], CAT[(22.59±3.01)U/ml vs.(25.12±3.3)U/ml, t=3.609, P=0.000]and reactive oxygen species[(74.13±5.02)pmol/L vs.(90.33±5.89)pmol/L, t=13.404, P=0.000]in the two groups were higher than those on the day before surgery, but were lower in the observation group than in the control group at the same time points after surgery.On the 3rd day after surgery, the levels of Tumor Necrosis Factor-α, C-reactive protein and interleukin 6 in the two groups were higher than those on the day before surgery, but were lower in the observation group than in the control group at the same points after surgery(all P<0.05). In the observation group, the incidence of complications was 14.63%, lower than 39.02% in the control group( χ2=6.212, P=0.013). Conclusions:The ERAS approach can achieve significant results in endometrial cancer patients treated with surgical staging.It can not only improve perioperative performance, relieve oxidative stress and lower inflammatory factor levels, but also effectively prevent complications.

Research and application progress of molecular detection technology in female tumor diagnosis / 中华检验医学杂志

The molecular detection technology shows a better application prospect and broad development in the early screening of female tumors, guiding the selection of therapeutic drugs, predicting prognosis and monitoring the efficacy of treatment. Numerous studies have demonstrated that molecular detection has great impact on the diagnosis and treatment strategies of female tumors such as breast cancer, cervical cancer, endometrial cancer and ovarian cancer. Previously, human papilloma virus detection has laid a foundation for clinical application for cervical cancer screening and breast cancer 1/2 mutation susceptibility gene detection to predict the risk of breast cancer and give drug guidance. These studies show the clinical application prospect of new molecular detection in the diagnosis and treatment of female tumors in the future.

Clinical molecular diagnosis of breast and female reproductive system tumors / 中华检验医学杂志

The gynecological tumours such as Breast cancer or female reproductive system tumors are a serious threat to female health. With the development of molecular diagnosis, the genomic changes of gynecological tumours have been revealed continuously, and the diagnosis and treatment modes of tumors have gradually changed. The detection of molecular targets which potentially participated in the transformation or progress of disease has become an important section of the management of female reproductive tumors, and accurate identification of molecular targets of tumors plays an important role in disease diagnosis, monitoring of metastasis, prediction of recurrence and treatment. This review briefly discusses the risk assessment, molecular typing, targeted therapy, toxic and side effects, and prognosis evaluation of breast and female reproductive system tumors by molecular diagnosis.

Application of DNA methylation in detection of endometrial carcinoma in women with abnormal uterine bleeding at childbearing age / 中华检验医学杂志

Objective:This work aims to explore the application value of cervical exfoliated cell DNA (Cysteine dioxygenase type 1, CDO1 and CUGBP Elav-like family member 4, CELF4) methylation in the detection of endometrial cancer in women of childbearing age. Methods:From November 2021 to October 2022, a prospective study was conducted on a total number of 517 reproductive-age women with abnormal uterine bleeding who had surgical indications for hysteroscopy at the Xiangya Third Hospital of Central South University. The cervical exfoliated cells were collected for cytology, HPV (human papillomavirus) and gene methylation detection before operation. Clinical information of patients, level of tumor-related biomarkers, and endometrial thickness of transvaginal ultrasound (TVS) were also collected. Single factor regression method was used to analyze the high-risk factors of endometrial cancer. Receiver operating characteristic curve analysis was used to obtain the area under the curve(AUC), focusing on the screening efficacy of gene methylation test for endometrial cancer in women of childbearing age.Results:The age, body mass index (BMI)≥25 kg/m 2, endometrial thickness≥11 mm, CDO1 m ΔCt≤8.4, CELF4 m ΔCt≤8.8, and double gene methylation were associated with endometrial cancer in women of childbearing age, 1.16(1.08-1.25), 4.33(1.89-10.31), 9.49(3.88-26.69), 69.62(25.70-224.36), 23.64(9.66-63.99), 87.39(24.83-555.05), all P<0.05. The AUC was 0.90 (95% CI 0.83-0.97) of CDO1 m/ CELF4 m in diagnosing endometrial carcinoma was higher than others factors, with sensitivity and specificity of 91.7% (95% CI 80.6%-100%) and 88.8% (95% CI 86.0%-91.6%). TVS combined with DNA methylation detection further improved the sensitivity to 95.8% (95% CI 87.8%-100%), but could not improve the specificity 68.0% (95% CI 63.8%-72.1%). Conclusions:For women of childbearing age with abnormal uterine bleeding or abnormal vaginal discharge, the accuracy of cervical cytology DNA methyl detection of endometrial cancer is better than other non-invasive clinical programs. DNA methylation combined with TVS can improve the sensitivity of detection.

Study on influencing factors of positive peritoneal cytology and its relationship with prognosis in patients with endometrial cancer / 肿瘤研究与临床

Objective:To investigate the risk factors of positive peritoneal cytology (PPC) in patients with endometrial cancer and the impact of PPC on patients' prognosis.Methods:The clinicopathological data of 202 patients who underwent initial surgical treatment and were diagnosed with endometrial cancer by postoperative pathology at Qilu Hospital of Shandong University from January 2015 to December 2019 were retrospectively analyzed, and the peritoneal fluid of patients were sent intraoperatively for cytological liquid-based smear examination. Logistic regression was used to perform univariate and multivariate analyses of PPC in the whole group of patients and the early-stage patients; Univariate analysis of the progression-free survival in the whole group of patients and the early-stage patients was performed by Kaplan-Meier method and compared by log-rank method, and multivariate analysis of the progression-free survival in the whole group of patients and the early-stage patients was performed by Cox proportional hazards model.Results:Of 202 patients, 183 (90.6%) had negative peritoneal cytology (NPC) and 19 (9.4%) had PPC; 180 patients (89.1%) were stage Ⅰ-Ⅱ and 22 (10.9%) were stage Ⅲ-Ⅳ; 180 patients (89.1%) had early-stage endometrial cancer. Deep myometrial infiltration ( OR = 3.57, 95% CI 1.02-12.45, P = 0.046) and lymph node metastasis ( OR = 7.16, 95% CI 1.70-30.23, P = 0.007) were independent risk factors for PPC in patients with endometrial cancer; deep myometrial infiltration was an independent risk factor for PPC in patients with early-stage endometrial cancer ( OR = 6.22, 95% CI 1.22-31.73, P = 0.028). The 3-year PFS rates for the whole group of patients with PPC and NPC were 72.9% and 92.7%, and the difference was statistically significant ( P = 0.001); the 3-year PFS rates for early-stage patients with PPC and NPC were 82.5% and 96.2%, and the difference was statistically significant ( P = 0.002). PPC was an independent risk factor for PFS in the whole group of patients with endometrial cancer ( HR = 4.80, 95% CI 1.14-20.17, P=0.032); PPC was also an independent risk factor for PFS in patients with early-stage endometrial cancer ( HR = 8.85, 95% CI 1.96-39.93, P = 0.005). Conclusions:Deep myometrial infiltration is an independent risk factor for PPC, and PPC is an independent risk factor for PFS in patients with endometrial cancer. Routine cytological examination of peritoneal fluid is recommended in patients with endometrial cancer.

Progress of relationship between body mass index and gynecological malignancies / 肿瘤研究与临床

Body mass index (BMI) is an index closely related to the total body fat. It is often used to measure the degree of obesity and reflect the nutritional status of the human body to a certain extent. The incidence rate and mortality rate of gynecological malignancies remain high. Some studies have found that BMI has certain value in the incidence and prognosis evaluation of gynecological malignancies, and is crucial to prolong the survival of patients. This review summarizes the recent research progress on the correlation between BMI and common gynecological malignancies and the mechanism of BMI on its occurrence and development.

Pathogenic mechanism and research progress of adipocytokines in endometrial cancer / 中国临床药理学与治疗学

Endometrial carcinoma (EC) is one of the most common gynecologic tumors, and its incidence and mortality are increasing.The prognosis is usually favorable when the disease is diagnosed at an early stage. However, the prognosis for patients with recurrence and metastasis is relatively poor. As one of the risk factors for EC, the complex and widespread oncogenic role of obesity in EC has been validated, then the oncogenic and pro-carcinogenic mechanisms of adipocytokines secreted by adipose tissue in EC have attracted continuous attention. This review highly summarizes and concludes the previous relevant literature on the role of adipocytokines in endometrial cancer and the progress of research，and elucidates the correlation between adipocytokines and the occurrence risk, stage grading, and long-term prognosis of EC, as well as their signaling pathways and mechanisms of action in the development of EC. All this information will likely contribute to the development of novel molecular markers in EC, the discovery of new therapeutic targets, and the study of related targeted drugs, which may in turn break the current dilemma of early screening, early diagnosis, and treatment of recurrent and metastatic patients in EC in the future, resulting in an improvement of the long-term prognosis of patients with EC.

miRNA-3653-3p reduces the proliferation and invasion ability of endometrial cancer cells by inhibiting PLAC8-Wnt-β-catenin signaling pathway / 肿瘤研究与临床

Objective:To investigate the effect of miRNA-3653-3p (miR-3653-3p) on the proliferation and invasion ability of endometrial cancer cells and its related mechanisms.Methods:The data of 356 endometrial cancer patients were downloaded from the OncoLnc database (http://www.oncolnc.org, updated version 2020), and the Kaplan-Meier method was used to analyze the relationship between the expression level of miR-3653-3p and the overall survival of endometrial cancer patients. The miRGator database (https://bio.tools/mirgator_v2.0, updated version 2019) was used to predict the target gene binding to miR-3653-3p. Human endometrial cancer cell lines AN3CA, HEC-1A, HEC-1B, Ishikawa and human normal endometrial epithelial cell line ESC were selected, and the relative expression level of miR-3653-3p was detected by using quantitative real-time fluorescent polymerase chain reaction (qRT-PCR). The cell line with the lowest expression of miR-3653-3p was selected as the research object, which was divided into the negative control group and miR-3653-3p group, and transfected with the control empty vector plasmid and miR-3653-3p overexpression plasmid. CCK-8 method was used to detect the proliferation ability of cells, Transwell method was used to detect the invasion ability of cells, and qRT-PCR and Western blot were used to detect the expression of miR-3653-3p target gene. The effect of miR-3653-3p on the related protein expression of Wnt- β-catenin signaling pathway was detected by using Western blot.Results:Data analysis in the OncoLnc database showed that compared with endometrial cancer patients with low miR-3653-3p expression, patients with high miR-3653-3p expression had better overall survival ( P < 0.01). Compared with human normal endometrial epithelial ESC, the expression levels of miR-3653-3p in endometrial cancer cell lines AN3CA, HEC-1A, HEC-1B, and Ishikawa were all decreased (all P < 0.05), and the relative expression level of miR-3653-3p was the lowest in HEC-1A cells, and HEC-1A cells were selected for subsequent experiments. The result of CCK-8 showed that compared with the negative control group, the ability of HEC-1A cells in the miR-3653-3p group decreased on the 2nd, 3rd, 4th, and 5th days (all P < 0.05). The result of the Transwell chamber invasion test showed that the number of HEC-1A cell invasion after culturing for 26 h in the negative control group and the miR-3653-3p group was (80±11) and (21±4), respectively, and the difference was statistically significant ( t = 5.18, P < 0.01); compared with the negative control group, the number of cell invasion in the miR-3653-3p group decreased. The miRGator database was used to predict that the target gene of miR-3653-3p might be placenta-specific protein 8 (PLAC8). The relative expression levels of PLAC8 mRNA in HEC-1A cells in the negative control group and miR-3653-3p group were (6.26±0.83) and (0.97±0.31), respectively, and the difference was statistically significant ( t = 6.00, P < 0.01); the relative expression level of PLAC8 mRNA in the miR-3653-3p group was lower than that in the negative control group. Compared with the negative control group, the PLAC8 protein of HEC-1A cells decreased, and the expression of Wnt-β-catenin signaling pathway related proteins β-catenin, transforming growth factor β (TGF-β), GSK-3β, and Rac1 decreased in the miR-3653-3p group. Conclusions:miR-3653-3p may inhibit the proliferation and invasion of endometrial cancer cells by regulating the PLAC8-Wnt-β-catenin signaling pathway.