Chao Wang

Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response

Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the management of early-onset endometrioid endometrial carcinoma (EEEC), particularly in patients under 40 who maintain both reproductive desire and capacity. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 patients with endometrial carcinoma, including 81 with EEEC. We reveal an unexpected association between exposome-related mutational signature and EEEC, characterized by specific CTNNB1 and SIGLEC10 hotspot mutations and disruption of downstream pathways. Interestingly, SIGLEC10

PTEN mutation predicts unfavorable fertility preserving treatment outcome in the young patients with endometrioid endometrial cancer and atypical hyperplasia

This study aimed to investigate the impact of molecular classification and PTEN, KRAS and PIK3CA gene mutation on the outcome of fertility-preserving treatment in the patients with endometrioid endometrial cancer (EEC) and endometrial atypical hyperplasia (EAH). This is a single-center retrospective study. A total of 135 patients with EEC and EAH receiving fertility-preserving treatment and molecular classification were reviewed. The distribution of the four types of molecular classification was described. The impact of non-specific molecular profile (NSMP), mismatch repair-deficiency (MMRd), and PTEN, KRAS and PIK3CA gene mutation on the outcome of fertility-preserving treatment was analyzed. Of the patients analyzed, 86.7% (117/136) were classified as having NSMP; 14 (10.4%), MMRd; 1 (0.7%), POLEmut EAH; and 3 (2.2%), p53abn EEC. The patients having NSMP and MMRd achieved similar 16-, 32-, and 48-week complete response rates. The patients harboring tier I and tier II PTEN mutations (PTENmut-Clin) achieved lower cumulative 32-week CR rates than those with PTEN-others (without PTENmut-Clin) (22/47, 46.8% vs. 50/74, 67.6%; p=0.023; odds ratio=0.422; 95% confidence interval [CI]=0.199-0.896). Insulin-resistance (hazard ratio [HR]=0.435; 95% CI=0.269-0.702; p=0.001) and PTENmut-Clin (HR=0.535; 95% CI=0.324-0.885; p=0.015) were independent negative predictors for lower 32-week CR rates. PTENmut-Clin is an independent risk factor for unfavorable fertility-preserving treatment outcomes in the patients with EEC and EAH. The patients with MMRd receiving fertility-preserving treatment achieved outcomes similar to those of the patients with NSMP. The molecular profiles might guide fertility-preserving treatment in the prognosis and clinical decisions.

Efficacy of sentinel lymph node mapping in endometrial cancer with low‐ or high‐intermediate risk

AbstractBackground and ObjectivesThis study was aimed to evaluate the efficacy of sentinel lymph node (SLN) mapping using indocyanine green (ICG) in Chinese women with endometrial cancer (EC).MethodsConsecutive EC patients undergoing SLN mapping at Obstetrics and Gynecology Hospital of Fudan University were retrospectively reviewed. Overall and bilateral SLN detection rates and SLN locations were presented. Sensitivity, negative predictive value (NPV), and agreement rate were calculated and were compared between patients with low‐intermediate (LIR) or high‐intermediate risk (HIR).ResultsThere were 454 patients screened, with SLN mapping with ICG performed in 428 patients and systematic lymphadenectomy performed in 159 patients. Overall and bilateral SLN detection rates were 96.50% and 82.71%, respectively. The sensitivity of SLN mapping was 80.00%, and the NPV was 97.76%. SLNs were most commonly located in obturator and external iliac regions. Efficacy of SLN mapping was higher in LIR patients than in HIR patients, with sensitivities of 100.00% and 75.00% (p > 0.05), NPVs of 100.00% and 90.00% (p = 0.002), and agreement rates of 100.00% and 92.31% (p = 0.007), respectively.ConclusionSLN mapping with ICG had acceptable diagnostic efficacy in Chinese women with EC, but may cause more missed diagnoses in patients with HIR due to relatively low NPV and agreement rate.

The efficiency of a combined injection technique for sentinel lymph node mapping in intermediate‐high‐risk endometrial cancer

AbstractBackground and ObjectivesSentinel lymph node (SLN) mapping was considered for treating endometrial cancer (EC) which was apparent confined to the uterus. Nevertheless, intermediate‐high‐risk EC patients have super high risk to undergo isolated para‐aortic lymph node metastases comparing with low‐risk patients. Therefore, this investigation aimed to compare the efficacy of two SLN methods in detecting para‐aortic lymph node metastases.MethodsAccording to SLN mapping injection methods, intermediate‐high‐risk EC patients who received both SLN mapping and systematic lymphadenectomy were divided into the combined group (fundal and cervical injections) and the cervical group (cervical injection only).ResultsThe para‐aortic SLN detection rate in the combined group (40.4%) was higher than that in the cervical group (4.4%) with p < 0.001. While the differences concerning the sensitivity, false‐negative rate, and negative predictive value between the two groups were not significant. The survival outcomes of patients were comparable between the two groups.ConclusionOur data showcased that the combined (fundal and cervical) injection had a higher detection rate of para‐aortic SLNs than cervical injection only. The efficiency of SLN mapping and the survival outcomes were not significantly different between the two groups. Further investigations are warranted to assess the value of combined injection regarding SLN technique.

Deep learning enhanced label-free cervical screening via stimulated Raman cytology

Cervical cancer screening remains pivotal for early detection and effective disease management, yet conventional cytopathological methods relying on stained cell-smear analysis face critical limitations in diagnostic throughput and sensitivity. We present a stain-free Visual-Aided Diagnosis via Stimulated Raman Cytology (VAD-SRC) platform that enables rapid cervical cell screening through simultaneous chemical and morphological profiling. By capturing intrinsic biomolecular contrast via stimulated Raman scattering (SRS) microscopy, our platform establishes malignancy-associated cellular fingerprints through quantitative analysis. Integrated with a deep convolutional neural network architecture, VAD-SRC achieves superb diagnostic performance (98.5 % accuracy, 100 % sensitivity) on an independent test set for binary classification of benign versus malignant cases. Moreover, its high-resolution segmentation function automates the identification of individual cancer cells within a mixture of five cell types: normal cells, leucocytes, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and squamous cervical cancer (SCC) cells. This advancement offers promising potential for cervical cancer screening and visual assessments within cytopathology workflows, enhancing diagnostic efficiency and precision.

Clinical Studies of Endometrial Cytology and Cervical Methylation Assays in Endometrial Cancer Screening and Fertility-Preservation Evaluation

The current study aims to assess high-risk patients using both liquid-based cytology and cervical methylation testing. The results will be compared with the traditional hysteroscopic pathological findings to determine the sensitivity and specificity of these methods for early detection of endometrial cancer, thereby evaluating their potential application in early screening. Primary Objectives： 1. To evaluate the sensitivity, specificity, and accuracy of endometrial cytology for screening endometrial cancer. 2. To assess the sensitivity, specificity, and accuracy of methylation testing for screening endometrial cancer. 3. To perform further molecular testing on tissue samples obtained from endometrial cytology and cervical methylation tests, aiming to explore early screening-sensitive indicators. Secondary Objectives： 1. To determine the value of endometrial cytology in evaluating the efficacy of fertility-sparing treatments for endometrial cancer. 2. To assess the value of methylation testing in evaluating the efficacy of fertility-sparing treatments for endometrial cancer.