Artificial intelligence-based models enabling accurate diagnosis of ovarian cancer using laboratory tests in China: a multicentre, retrospective cohort study.

BACKGROUND: Ovarian cancer is the most lethal gynecological malignancy. Timely diagnosis of ovarian cancer is difficult due to the lack of effective biomarkers. Laboratory tests are widely applied in clinical practice, and some have shown diagnostic and prognostic relevance to ovarian cancer. We aimed to systematically evaluate the value of routine laboratory tests on the prediction of ovarian cancer, and develop a robust and generalisable ensemble artificial intelligence (AI) model to assist in identifying patients with ovarian cancer. METHODS: In this multicentre, retrospective cohort study, we collected 98 laboratory tests and clinical features of women with or without ovarian cancer admitted to three hospitals in China during Jan 1, 2012 and April 4, 2021. A multi-criteria decision making-based classification fusion (MCF) risk prediction framework was used to make a model that combined estimations from 20 AI classification models to reach an integrated prediction tool developed for ovarian cancer diagnosis. It was evaluated on an internal validation set (3007 individuals) and two external validation sets (5641 and 2344 individuals). The primary outcome was the prediction accuracy of the model in identifying ovarian cancer. FINDINGS: Based on 52 features (51 laboratory tests and age), the MCF achieved an area under the receiver-operating characteristic curve (AUC) of 0·949 (95% CI 0·948-0·950) in the internal validation set, and AUCs of 0·882 (0·880-0·885) and 0·884 (0·882-0·887) in the two external validation sets. The model showed higher AUC and sensitivity compared with CA125 and HE4 in identifying ovarian cancer, especially in patients with early-stage ovarian cancer. The MCF also yielded acceptable prediction accuracy with the exclusion of highly ranked laboratory tests that indicate ovarian cancer, such as CA125 and other tumour markers, and outperformed state-of-the-art models in ovarian cancer prediction. The MCF was wrapped as an ovarian cancer prediction tool, and made publicly available to provide estimated probability of ovarian cancer with input laboratory test values. INTERPRETATION: The MCF model consistently achieved satisfactory performance in ovarian cancer prediction when using laboratory tests from the three validation sets. This model offers a low-cost, easily accessible, and accurate diagnostic tool for ovarian cancer. The included laboratory tests, not only CA125 which was the highest ranked laboratory test in importance of diagnostic assistance, contributed to the characterisation of patients with ovarian cancer. FUNDING: Ministry of Science and Technology of China; National Natural Science Foundation of China; Natural Science Foundation of Guangdong Province, China; and Science and Technology Project of Guangzhou, China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Mitophagy genes in ovarian cancer: a comprehensive analysis for improved immunotherapy.

BACKGROUND: Mitophagy is a process of selectively degrading damaged mitochondria, which has been found to be related to immunity, tumorigenesis, tumor progression, and metastasis. However, the role of mitophagy-related genes (MRGs) in the tumor microenvironment (TME) of ovarian cancer (OV) remains largely unexplored. METHODS: We analyzed the expression, prognosis, and genetic alterations of 29 MRGs in 480 OV samples. Unsupervised clustering was used to classify OV into two subtypes (clusters A and B) based on MRG changes. We compared the clinical features, differential expressed genes (DEGs), pathways, and immune cell infiltration between the two clusters. We constructed a mitophagy scoring system (MRG_score) based on the DEGs and validated its ability to predict overall survival of OV patients. RESULTS: We found that patients with high MRG_scores had better survival status and increased infiltration by immune cells. Further analysis showed that these patients may be more sensitive to immune checkpoint inhibitor (ICI) treatment. Additionally, the MRG_score significantly correlated with the sensitivity of chemotherapeutic drugs and targeted inhibitors. CONCLUSION: Our comprehensive analysis of MRGs in the TME, clinical features, and patient prognosis revealed that the MRG_score is a potentially effective prognostic biomarker and predictor of treatment. This study provides new insights into the role of MRGs in OV and identifies patients who may benefit from ICI treatment, chemotherapy, or targeted treatment.

Impact of different post-operative treatment modalities on long-term outcomes in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIICp cervical cancer.

OBJECTIVE: This retrospective study aimed to evaluate the survival outcomes in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIICp cervical cancer patients receiving different adjuvant treatment modalities after radical hysterectomy. METHODS: From January 2008 to December 2012, patients diagnosed with cervical cancer who underwent radical hysterectomy plus retroperitoneal lymphadenectomy with pathologically confirmed positive lymph nodes, and received either radiotherapy, concurrent chemoradiation, or sequential chemoradiation, were included in this study. Survival analysis was performed according to different adjuvant treatment modalities and after adjustment using propensity score matching. RESULTS: A total of 192 stage IIICp cervical cancer patients were eligible. In multivariate analysis, only sequential chemoradiation versus radiotherapy was associated with both overall survival (HR 0.44, 95% CI 0.21 to 0.94, p=0.035) and disease-free survival (HR 0.26, 95% CI 0.11 to 0.57, p<0.001). The 5-year overall survival for radiotherapy, concurrent chemoradiation, and sequential chemoradiation was 71.6%, 81.7%, and 81.5%, respectively. No significant difference in overall survival was noted between the three groups (radiotherapy vs concurrent chemoradiation, p=0.15; radiotherapy vs sequential chemoradiation, p=0.09; concurrent chemoradiation vs sequential chemoradiation, p=0.95). However, sequential chemoradiation significantly increased disease-free survival compared with radiotherapy alone (79.2% vs 63.1%, p=0.028). After propensity score matching in the baseline characteristics, both overall survival (88.0% vs 71.6%, p=0.028) and disease-free survival (88.0% vs 63.1%, p=0.021) were improved in the sequential chemoradiation group compared with radiotherapy alone; no significant differences were noted between sequential chemoradiation and concurrent chemoradiation (overall survival 88.0% vs 83.8%, p=0.50; disease-free survival 88.0% vs 75.8%, p=0.28). CONCLUSION: In this cohort of FIGO 2018 IIICp cervical cancer patients, post-operative sequential chemoradiation was associated with higher survival compared with radiotherapy alone after propensity matching. Future prospective studies are required to further elucidate the optimal modality in node-positive cervical cancer.

Preoperative and intraoperative assessment of myometrial invasion in patients with FIGO stage I non-endometrioid endometrial carcinoma-a large-scale, multi-center, and retrospective study.

INTRODUCTION: Myometrial invasion is a prognostic factor for lymph node metastases and decreased survival in non-endometrioid endometrial carcinoma patients. Herein, we explored the mode of myometrial invasion diagnosis in FIGO stage I non-endometrioid carcinoma and evaluated the differences in diagnostic efficiency among intraoperative frozen section (IFS), intraoperative gross examination (IGE), magnetic resonance imaging (MRI), and computed tomography (CT) in clinical practice. Finally, we suggested which test should be routinely performed. METHOD: This was a historical cohort study nationwide with 30 centers in China between January 2000 and December 2019. Clinical data, including age, histology, method of myometrial invasion evaluation (MRI, CT, IGE, and IFS), and final diagnosis of postoperative paraffin sections, were collected from 490 non-endometrioid endometrial carcinoma (serous, clear cell, undifferentiated, mixed carcinoma, and carcinosarcoma) women in FIGO stage I. RESULTS: Among the 490 patients, 89.59% presented myometrial invasion. The methods reported for myometrial invasion assessment were IFS in 23.47%, IGE in 69.59%, MRI in 37.96%, and CT in 10.20% of cases. The highest concordance was detected between IFS and postoperative paraffin sections (Kappa = 0.631, accuracy = 93.04%), followed by IGE (Kappa = 0.303, accuracy = 82.40%), MRI (Kappa = 0.131, accuracy = 69.35%), and CT (Kappa = 0.118, accuracy = 50.00%). A stable diagnostic agreement between IFS and the final results was also found through the years (2000-2012: Kappa = 0.776; 2013-2014: Kappa = 0.625; 2015-2016: Kappa = 0.545; 2017-2019: Kappa = 0.652). CONCLUSION: In China, the assessment of myometrial invasion in non-endometrioid endometrial carcinoma is often performed via IGE, but the reliability is relatively low in contrast to IFS. In clinical practice, IFS is a reliable method that can help accurately assess myometrial invasion and intraoperative decision-making (lymph node dissection or not). Hence, it should be routinely performed in non-endometrioid endometrial carcinoma patients.

It is not the time to abandon intraoperative frozen section in endometrioid adenocarcinoma: A large-scale, multi-center, and retrospective study.

INTRODUCTION: Stage IB (deep myometrial invasion) high-grade endometrioid adenocarcinoma (EA), regardless of LVSI status, is classified into high-intermediate risk groups, requiring surgical lymph node staging. Intraoperative frozen section (IFS) is commonly used, but its adequacy and reliability vary between reports. Hence, we determined the utility of IFS in identification of high-risk factors, including deep myometrial invasion and high-grade. METHOD: We retrospectively analyzed 9,985 cases operated with hysterectomy and diagnosed with FIGO stage I/II EA in postoperative paraffin section (PS) results at 30 Chinese hospitals from 2000 to 2019. We determined diagnostic performance of IFS and investigated whether the addition of IFS to preoperative biopsy and imaging could improve identification of high-risk factors. RESULTS: IFS and postoperative PS presented the highest concordance in assessing deep myometrial invasion (Kappa: 0.834), followed by intraoperative gross examination (IGE Kappa: 0.643), MRI (Kappa: 0.395), and CT (Kappa: 0.207). IFS and postoperative PS presented the highest concordance for high-grade EA (Kappa: 0.585) compared to diagnostic curettage (D&C 0.226) and hysteroscope (Hys 0.180). Sensitivity and specificity for detecting deep myometrial invasion were 86.21 and 97.20% for IFS versus 51.72 and 88.81% for MRI, 68.97 and 94.41% for IGE. These figures for detecting high-grade EA were 58.21 and 96.50% for IFS versus 16.42 and 98.83% for D&C, 13.43 and 98.64% for Hys. Parallel strategies, including MRI-IFS (Kappa: 0.626), D&C-IFS (Kappa: 0.595), and Hys-IFS (Kappa: 0.578) improved the diagnostic efficiencies of individual preoperative examinations. Based on the high sensitivity of IFS, parallel strategies improved the sensitivities of preoperative examinations to 89.66% (MRI), 64.18% (D&C), 62.69% (Hys), respectively, and these differences were statistically significant (p = 0.000). CONCLUSION: IFS presented reasonable agreement rates predicting postoperative PS results, including deep myometrial invasion and high-grade. IFS helps identify high-intermediate risk patients in preoperative biopsy and MRI and guides intraoperative lymphadenectomy decisions in EA.

A novel combination of niraparib and anlotinib in platinum-resistant ovarian cancer: Efficacy and safety results from the phase II, multi-center ANNIE study.

Background: Patients with platinum-resistant recurrent ovarian cancer (PROC) face poor prognosis and limited treatment options. Single-agent antiangiogenics and poly (ADP-ribose) polymerase (PARP) inhibitors both show some activities in platinum-resistant diseases. The ANNIE study aimed to evaluate the efficacy and safety of the novel combination of the PARP inhibitor niraparib and the antiangiogenic anlotinib in patients with PROC. Methods: ANNIE is a multicentre, single-arm, phase 2 study (ClinicalTrials.gov identifier NCT04376073) conducted at three hospitals in China. Eligible patients had histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal cancer that recurred within 6 months of last platinum-based chemotherapy. Patients with prior PARP inhibitor exposure were excluded. The enrolled patients received oral niraparib 200 mg or 300 mg (baseline body weight-directed) once daily continuously and anlotinib 10 mg (12 mg before protocol amendment) once daily on days 1-14 of each 21-day cycle until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR). Findings: Between May 22, 2020, and April 22, 2021, 40 patients were enrolled and treated. Thirty-six patients underwent post-baseline tumour assessments. By data cut-off (January 31, 2022), median follow-up was 15.4 months (95% CI 12.6-17.7). Intention-to-treat ORR was 50.0% (95% CI 33.8-66.2), including one complete response and 19 partial responses. Median (95% CI) progression-free survival and overall survival were 9.2 months (7.4-11.9) and 15.3 months (13.9-not evaluable), respectively. Drug-related, grade ≥3 TEAEs were reported in 26 (68%) patients. There were no treatment-related deaths. Interpretation: Niraparib plus anlotinib showed promising antitumour activity in patients with PROC. This oral combination warrants further investigation as a potential novel, convenient treatment option for patients with PROC. Funding: Zai Lab (Shanghai) Co., Ltd; Jiangsu Chia Tai-Tianqing Pharmaceutical Co., Ltd; the National Natural Science Foundation of China (No. 82102783).

TRAF4 promotes the malignant progression of high-grade serous ovarian cancer by activating YAP pathway.

High-grade serous ovarian cancer (HGSOC) accounts for the majority of deaths caused by epithelial ovarian cancer. The specific molecular changes attributable to the pathogenesis of HGSOC are still largely unknown. TRAF4 has been identified to be up-regulated in certain cancers. However, the role and mechanism of TRAF4 in HGSOC remain unclear. In this study, we aim to explore the prognostic value and function of TRAF4 in HGSOC. Immunohistochemical staining and prognostic analysis were used to estimate the prognosis value of TRAF4 in HGSOC. Cell counting assays, colony formation assays, sphere formation assays and tumorigenic assays were used to explore the function of TRAF4 in ovarian cancer cells. Furthermore, RNA-seq, qPCR and western blotting were performed to investigate the molecular mechanism of TRAF4 in ovarian cancer cells. The results showed that TRAF4 was significantly higher expressed in ovarian cancer than normal ovarian epithelium. Moreover, high expression of TRAF4 was significantly associated with shorter overall survival and recurrence-free survival in HGSOC. Knockdown of TRAF4 significantly inhibited the proliferation and tumorigenicity of ovarian cancer cells, whereas overexpression of TRAF4 promoted the proliferation and tumorigenicity of ovarian cancer cells both in vitro and in vivo. Mechanistically, our study demonstrated that TRAF4 expression was positively correlated with the YAP pathway gene signatures, and the malignant progression induced by TRAF4 was inhibited after silencing YAP signaling by its selective inhibitor. In conclusion, our findings suggested that TRAF4 promoted the malignant progression of ovarian cancer cells by activating YAP pathway and might serve as a prognostic biomarker for HGSOC.

Risk Factors and Prognosis of Early Recurrence in Stage I-II Endometrial Cancer: A Large-Scale, Multi-Center, and Retrospective Study.

Objective: The aim of the present study was to determine overall survival (OS) and risk factors associated with early recurrence in patients with FIGO I-II stage endometrial carcinoma (EC). Methods: Clinical features were retrospectively extracted from the database of China Endometrial Cancer Consortium from January 2000 to December 2019. A total of 2,974 patients with Federation International of Gynecology and Obstetrics (FIGO) I-II stage endometrial cancer were included. Kaplan-Meier survival analysis was used to assess OS and disease-specific survival. Cox proportional hazard model and Fine-Gray model were used to determine the factors related to OS. Binary logistic regression model was used to determine independent predictors of early relapse patients. Results: Of these 2,974 ECs, 189 patients were confirmed to have relapse. The 5-year OS was significantly different between the recurrence and non-recurrence patients (p < 0.001). Three quarters of the relapse patients were reported in 36 months. The 5-year OS for early recurrence patients was shorter than late recurrence [relapse beyond 36 months, p < 0.001]. The grade 3 [odds ratio (OR) = 1.55, 95%CI 1.17-2.05, p = 0.002], lymphatic vascular infiltration (LVSI; OR = 3.36; 95%CI 1.50-7.54, p = 0.003), and myometrial infiltration (OR = 2.07, 95%CI 1.17-3.65, p = 0.012) were independent risk factors of early relapse. The protective factor of that is progesterone receptor (PR)-positive (OR = 0.50, 95%CI 0.27-0.92, p = 0.02). Bilateral ovariectomy could reduce recurrence risk rate (OR = 0.26, 95%CI 0.14-0.51, p < 0.001). Conclusion: The OS of early relapse EC is worse. Grade 3, LVSI, and myometrial infiltration are independent risk factors for early relapse EC. In addition, the protective factor is PR-positive for those people and bilateral salpingo-oophorectomy could reduce the risk of recurrence.

Prognostic-Related Metabolic Score for Survival Prediction in Early-Stage Endometrioid Endometrial Cancer: A Multi-Center and Retrospective Study.

Objective: Patients with endometrial cancer (EC) combined with metabolic syndrome (MetS) have a worse prognosis than those without MetS. This study aimed to investigate whether partial metabolic disorder significantly influenced early-stage endometrioid EC (EEC) survival and searched for a more efficient method to evaluate metabolic status. Methods: This is a nationwide, multicenter cohort study that included 998 patients with primary early-stage EEC from 2001 to 2018. Patients were divided into different metabolic groups based on the diagnostic criteria of the Chinese Medical Association (CDC). The progression-free survival (PFS) time was compared between various metabolic status. Meanwhile, we established an EC Prognostic-Related Metabolic Score (ECPRM Score) to explore the association of the severity of metabolic status and early-stage EEC PFS. A nomogram was established for predicting PFS, which was externally validated in a testing set that includes 296 patients. Results: A partial metabolic disorder, as well as MetS, was an independent risk factor of poor survival of patients with early-stage EEC [hazard ratio (HR) = 7.6, 95% CI = 1.01-57.5, p < 0.05]. A high ECPRM Score was associated with lower PFS (HR = 2.1, 95% CI = 1.05-4.0, p < 0.001). The nomogram, in which the ECPRM Score contributed most to the prognosis, exhibited excellent discrimination of survival supported by the internal and external validations. In addition, the calibration curve supports its robust predicting ability. Conclusion: Even though they do not meet the criteria of MetS, partial metabolic disorders were also associated with adverse outcomes in early-stage EEC. The ECPRM Score is beneficial for clinicians to evaluate the severity of metabolic abnormalities and guide patients to ameliorate the poor prognosis of metabolic disorders.

Implications of Isolated Para-Aortic Lymph Node Metastasis in Endometrial Cancer: A Large-Scale, Multicenter, and Retrospective Study.

Objective: To systematically evaluate lymph node metastasis (LNM) patterns in patients with endometrial cancer (EC) who underwent complete surgical staging, which included systematic pelvic and para-aortic lymphadenectomy. Methods: Four thousand and one patients who underwent complete surgical staging including systematic pelvic and para-aortic lymphadenectomy for EC were enrolled from 30 centers in China from 2001 to 2019. We systematically displayed the clinical and prognostic characteristics of patients with various LNM patterns, especially the PLN-PAN+ [para-aortic lymph node (PAN) metastasis without pelvic lymph node (PLN) metastasis]. The efficacy of PAN+ (para-aortic lymph node metastasis) prediction with clinical and pathological features was evaluated. Results: Overall, 431 of the 4,001 patients (10.8%) showed definite LNM according to pathological diagnosis. The PAN+ showed the highest frequency (6.6%) among all metastatic sites. One hundred fourteen cases (26.5%) were PLN-PAN+ (PAN metastasis without PLN metastasis), 167 cases (38.7%) showed PLN+PAN-(PLN metastasis without PAN metastasis), and 150 cases (34.8%) showed metastasis to both regions (PLN+PAN+). There was also 1.9% (51/2,660) of low-risk patients who had PLN-PAN+. There are no statistical differences in relapse-free survival (RFS) and disease-specific survival (DSS) among PLN+PAN-, PLN-PAN+, and PLN+PAN+. The sensitivity of gross PLNs, gross PANs, and lymphovascular space involvement (LVSI) to predict PAN+ was 53.8 [95% confidence interval (CI): 47.6-59.9], 74.2 95% CI: 65.6-81.4), and 45.8% (95% CI: 38.7-53.2), respectively. Conclusion: Over one-fourth of EC patients with LMN metastases were PLN-PAN+. PLN-PAN+ shares approximate survival outcomes (RFS and DSS) with other LNM patterns. No effective clinical methods were achieved for predicting PAN+. Thus, PLN-PAN+ is a non-negligible LNM pattern that cannot be underestimated in EC, even in low-risk patients.

Comparison of PARPis with Angiogenesis Inhibitors and Chemotherapy for Maintenance in Ovarian Cancer: A Network Meta-Analysis.

INTRODUCTION: Seventy-five percent of ovarian cancer would relapse within 18-28 months after platinum-base chemotherapy. Evidence suggests that maintenance chemotherapy is effective in prolonging remission. Recent target therapies such as poly(ADP-ribose) polymerase inhibitors (PARPis) and angiogenesis inhibitors (AIs) are known to ease burden and recurrence of ovarian cancer. There is limited data for head-to-head comparison of PARPis, AIs, and chemotherapeutic agents (CTAs) as maintenance treatment. This network meta-analysis thus assessed the effectiveness and toxicity of these three maintenance therapies in patients with ovarian cancer. METHODS: We searched relevant sources (PubMed, EMBASE) to identify randomized controlled trials assessing efficacy and safety of maintenance therapy in patients with ovarian cancer. Primary outcome was progression-free survival (PFS) as assessed by blinded review; safety and tolerability were secondary outcomes. A network meta-analysis to compare three drug classes was performed using statistical software R. RESULTS: We included 24 trials (11,366 patients) assessing efficacy and safety of PARPis (n = 4), AIs (n = 12), and CTAs (n = 8). PARPis [hazard ratio (HR) 0.64; 95% credible intervals (CrI) 0.55-0.73] and AIs (HR 0.87; 95% CrI 0.81-0.93) showed significant improvement in PFS compared to placebo but not CTA (HR 1.00; 95% CrI 0.86-1.15). PARPis showed significant improvement in PFS compared to AIs (HR 0.73; 95% CrI 0.63-0.86) and CTA (HR 0.64; 95% CrI 0.52-0.78). Adverse events (AEs) leading to treatment discontinuation and dose reduction were lower in PARPis [incidence rate ratio (IRR) 0.60; CrI 0.31-1.18 and IRR 0.73, 95% CrI 0.50-1.06, respectively] compared to AIs, but the differences were not significant. CONCLUSION: PARPi as maintenance treatment improved PFS in ovarian cancer and was relatively safer in terms of implications caused by AEs when compared to AIs. This network meta-analysis provides valuable evidence and significant insights into treatment of ovarian cancer.

The Expression and Function of NUMB in Endometrial Cancer and the Interaction with HDM2 and P53.

BACKGROUND: Since more and more evidences support that NUMB orchestrates many cell physiological and pathological processes of diseases including cancer, based on our previous work, we studied deeply the function of NUMB in endometrial cancer (EC) and tried to understand the mechanism of NUMB's nucleus translocation which might be relative to the occurrence of EC and will contribute to find a new targeting therapeutic strategy for EC. METHODS: Immunohistochemistry was employed to test NUMB and HDM2 expression in endometrial cancer tissue from clinical patients. CCK-8 assay, cell cycle tested by Flow cytometer and PCNA determined by RT-PCR were employed to test the effects of NUMB on cell proliferation and apoptosis. In order to investigate the mechanism how NUMB, HDM2 and p53 interact in EC cell, western blot, Co-IP and immunofluorescent were used to observe the combination and location of NUMB, HDM2 and p53 as well as the interaction among them. RESULTS: Both NUMB and HDM2 expressed greater in endometrial cancer tissues than in normal endometrial tissues. Overexpression of NUMB induced apoptosis in Ishikawa cell while inhibition of NUMB increased cell proliferation. NUMB could combine HDM2 and p53, moreover the PTB domain of NUMB is the main site combining with p53. The effects of NUMB in cell was closely associated with p53. Not only NUMB regulated P53 expression level but also NUMB acts depending on P53, in turn p53 impacted the NUMB level as a feedback. Overexpression of NUMB could not bring itself into nuclear. Both siHDM2 and siP53 didn't bring NUMB into nucleus, However overexpression of HDM2 and p53 increased the NUMB level in nucleus, and the NUMB nuclear location induced by overexpression of HDM2 was stronger than that of p53 overexpression. CONCLUSIONS: Based on present data, we think NUMB acts as an anti-oncogene role and could regulate p53 level and function in endometrial cancer like in other cancers, meanwhile, the function of NUMB depend on P53. On the other hand, the location of NUMB could be regulated mainly by HDM2. So far we are not able to explain why endometrial cancer patients had high NUMB expression level since NUMB was regarded as a tumor suppressor, which is worthy studying further to explore underlying mechanism.

Uterine carcinosarcoma and high-risk endometrial carcinomas: a clinicopathological comparison.

OBJECTIVE: This retrospective study aimed to evaluate the clinicopathological characteristics of carcinosarcoma, grade 3 endometrial endometrioid carcinoma (G3EEC), uterine serous carcinoma (USC), and uterine clear cell adenocarcinoma (CC) to determine whether carcinosarcoma exhibited the same characteristics and outcomes as the other 3 high-risk endometrial cancers. METHODS: A total of 358 patients recruited from the Obstetrics and Gynecology Hospital of Fudan University were included in this study; the cases included 44 carcinosarcomas, 118 G3EECs, 118 USCs, and 78 CCs. Kaplan-Meier and Cox proportional hazards models were used to analyze outcomes and prognostic factors. RESULTS: Uterine carcinosarcomas had significantly worse outcomes (overall survival, disease-specific survival, and recurrence-free survival) compared with G3EEC, USC, and CC (P < 0.001), whereas the other 3 shared similar outcomes. Carcinosarcoma type was an independent factor, even stratified by stage. Eighty-three percent of recurred carcinosarcoma patients occurred within 1 year. Compared with USC and CC, patients with carcinosarcoma had a greater incidence of deep myometrial invasion (55.8%, P < 0.05) and cervical stromal involvement (P = 0.046). The carcinomatous regions of carcinosarcomas demonstrated a similar ER/P53 expression pattern as did USC and CC. However, all features were similar in carcinosarcoma and G3EEC patients, although the P53-positive rate was higher in carcinosarcoma patients compared with G3EEC patients (59.0% vs 38.5%, P = 0.037). For carcinosarcomas, a multivariate analysis showed that advanced stage (P = 0.006) was an independent prognostic factor for disease-specific survival. With regard to endometrioid-or-not epithelial and heterologous-or-homologous sarcomatous components, none of these components demonstrated apparent relationship with prognosis. CONCLUSIONS: Carcinosarcomas exhibited significantly poorer outcomes than did G3EECs, USCs, and CCs. Therefore, it seems reasonable to regard carcinosarcomas as a particular type among high-risk epithelial endometrial carcinomas.

Clinicopathological risk factors for pelvic lymph node metastasis in clinical early-stage endometrioid endometrial adenocarcinoma.

OBJECTIVE: To identify the clinicopathological risk factors for pelvic lymph node (PLN) metastasis and to evaluate the predictive significance of these factors for lymphadenectomy in clinical early-stage endometrioid endometrial adenocarcinoma (EEA). METHODS: Six hundred and twenty-one patients with clinical early-stage EEA (tumor confined to uterus, diagnosed preoperatively or intraoperatively) who underwent hysterectomy plus bilateral salpingo-oophorectomy plus pelvic and/or para-aortic lymphadenectomy between 1989 and 2006 in the Obstetrics and Gynecology Hospital of Fudan University were retrieved. The predictive value of the risk factors for PLN metastasis was analyzed. RESULTS: The positive PLN metastasis rate was 3.9%. The 5-year disease-related mortality rate in the positive PLN metastasis group was 25%, whereas the rate in the negative group was 0.8%. The positive PLN metastasis rates were higher in patients with higher-grade tumors, deep myometrial invasion, cervical stromal involvement, and lymphovascular space involvement (LVSI). The sensitivity and specificity of old age (≥ 60 years), grade 3, cancer deep myometrial invasion, cervical stromal involvement, and LVSI in predicting the PLN metastasis were 25.0%, 41.7%, 70.8%, 20.8%, and 41.7%; and 79.1%, 88.4%, 85.6%, 95.6%, and 94.5%, respectively. The multivariate analysis revealed that the deep myometrial invasion and LVSI were independent risk factors for lymph node metastasis. Combined with these 2 factors as the diagnostic criteria, the negative predictive value and specificity were 97.3% and 89.1%, respectively. CONCLUSION: The patients with clinical early-stage EEA with PLN metastasis showed worse prognoses, although the metastasis rate was low. The deep myometrial invasion and LVSI combination were superior predictive criteria for the PLN metastasis. An accurate evaluation of these factors, both preoperatively or intraoperatively, will be beneficial to predict PLN metastasis and guide the operation.