Consistency between Primary Uterine Corpus Malignancies and Their Corresponding Patient-Derived Xenograft Models.

Patient-derived xenograft (PDX) models retain the characteristics of tumors and are useful tools for personalized therapy and translational research. In this study, we aimed to establish PDX models for uterine corpus malignancies (UC-PDX) and analyze their similarities. Tissue fragments obtained from 92 patients with uterine corpus malignancies were transplanted subcutaneously into immunodeficient mice. Histological and immunohistochemical analyses were performed to compare tumors of patients with PDX tumors. DNA and RNA sequencing were performed to validate the genetic profile. Furthermore, the RNA in extracellular vesicles (EVs) extracted from primary and PDX tumors was analyzed. Among the 92 cases, 52 UC-PDX models were established, with a success rate of 56.5%. The success rate depended on tumor histology and staging. The pathological and immunohistochemical features of primary and PDX tumors were similar. DNA sequencing revealed similarities in gene mutations between the primary and PDX tumors. RNA sequencing showed similarities in gene expressions between primary and PDX tumors. Furthermore, the RNA profiles of the EVs obtained from primary and PDX tumors were similar. As UC-PDX retained the pathological and immunohistochemical features and gene profiles of primary tumors, they may provide a platform for developing personalized medicine and translational research.

Cancer-Specific miRNAs Extracted from Tissue-Exudative Extracellular Vesicles in Ovarian Clear Cell Carcinoma.

Ovarian clear cell carcinomas (OCCs) arise from endometriotic cysts that many women develop. Biomarkers for early OCC detection need to be identified. Extracellular vesicles have attracted attention as biomarker carriers. This study aims to identify cancer-specific miRNAs as novel OCC biomarkers using tissue-exudative extracellular vesicles (Te-EVs). Te-EVs were collected from four patients with OCC on one side and a normal ovary on the other side. Microarray analysis was performed to identify cancer-specific miRNAs in Te-EVs. Serum samples obtained before and after surgery from patients with OCC and atypical endometrial hyperplasia (AEH) (controls) were compared using real-time PCR to examine changes in the detected EV miRNA levels. Thirty-seven miRNAs were >2-fold upregulated on the OCC side compared with the normal ovarian side. We selected 17 miRNAs and created specific primers for 12 of these miRNAs. The levels of six EV miRNAs were significantly decreased in postoperative OCC serum compared to those in preoperative OCC serum. In contrast, no significant change was observed between the pre and postoperative values in the control group. We identified OCC tissue-specific miRNAs in the EVs secreted by OCC tissues. These EV miRNAs have potential for use as biomarkers for the early diagnosis and detection of OCC.

Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience.

Background: The application of personalized cancer treatment based on genetic information and surgical samples has begun in the field of cancer medicine. However, a biopsy may be painful for patients with advanced diseases that do not qualify for surgical resection. Patient-derived xenografts (PDXs) are cancer models in which patient samples are transplanted into immunodeficient mice. PDXs are expected to be useful for personalized medicine. The aim of this study was to establish a PDX from body fluid (PDX-BF), such as peritoneal and pleural effusion samples, to provide personalized medicine without surgery. Methods: PDXs-BF were created from patients with ovarian cancer who had positive cytology findings based on peritoneal and pleural effusion samples. PDXs were also prepared from each primary tumor. The pathological findings based on immunohistochemistry were compared between the primary tumor, PDX, and PDX-BF. Further, genomic profiles and gene expression were evaluated using DNA and RNA sequencing to compare primary tumors, PDXs, and PDX-BF. Results: Among the 15 patients, PDX-BF was established for 8 patients (5 high-grade serous carcinoma, 1 carcinosarcoma, 1 low-grade serous carcinoma, and 1 clear cell carcinoma); the success rate was 53%. Histologically, PDXs-BF have features similar to those of primary tumors and PDXs. In particular, PDXs-BF had similar gene mutations and expression patterns to primary tumors and PDXs. Conclusions: PDX-BF reproduced primary tumors in terms of pathological features and genomic profiles, including gene mutation and expression. Thus, PDX-BF may be a potential alternative to surgical resection for patients with advanced disease.

Oncologic Outcomes of Patients with Early-Stage Cervical Cancer after Minimally Invasive Radical Hysterectomy and Sentinel Lymph Node Biopsy.

Background: The sentinel lymph node is the first node that cancer cells reach when migrating from the primary site. However, oncological outcomes after sentinel lymph node biopsy (SNB) have not been reported for cervical cancer. In this study, oncological outcomes were compared between patients receiving SNB and pelvic lymphadenectomy (PLD) for early-stage cervical cancer. Methods: One hundred and four patients with clinical stage 1A2, 1B1, and 2A1 cervical cancer were included in this study. All patients underwent laparoscopic or robot-assisted radical hysterectomy with SNB or PLD. Fifty-two patients with tumors ≤2 cm underwent SNB. Disease-free survival (DFS) and overall survival (OS) were compared between the groups. Results: The median (interquartile range) tumor size was 12 (7-20) mm in the SNB group and 20 (13-25) mm in the PLD group. Lymph node metastasis occurred in one patient in the SNB group and in nine patients in the PLD group. The median follow-up periods were 42 (24-60) and 82 (19-101) months in the SNB group and PLD group, respectively. The 3-year DFS rates were 100% in SNB and 91.5% in PLD. The 3-year OS was 100% in both groups. Conclusions: SNB was sufficient in cervical cancer patients with tumors ≤2 cm, suggesting that PLD might not be necessary for these patients.

Lymphatic Complications Following Sentinel Node Biopsy or Pelvic Lymphadenectomy for Endometrial Cancer.

Sentinel node biopsy (SNB) is performed worldwide in patients with endometrial cancer (EC). The aim of this study was to evaluate and compare the occurrence rate of lymphatic complications between SNB and pelvic lymphadenectomy (LND) for EC. The medical records of women who underwent SNB or pelvic LND for EC between September 2012 and April 2022 were assessed. A total of 388 patients were enrolled in the current study. Among them, 201 patients underwent SNB and 187 patients underwent pelvic LND. The occurrence rates of lower-extremity lymphedema (LEL) and pelvic lymphocele (PL) were compared between the patients who underwent SNB and those who underwent pelvic LND. The SNB group had a significantly lower occurrence rate of lower-extremity LEL than the pelvic LND group (2.0% vs. 21.3%, p < 0.01). There were no patients who had PL in the SNB group; however, 4 (2.1%) patients in the pelvic LND group had PL. The occurrence rates of lower-extremity LEL and PL were significantly lower in patients who underwent SNB than those who underwent pelvic LND. SNB for EC has a lower risk of lymphatic complications compared to systemic LND.

Which is better for predicting pelvic lymph node metastases in patients with cervical cancer: Fluorodeoxyglucose-positron emission tomography/computed tomography or a sentinel node biopsy? A retrospective observational study.

Systematic pelvic lymph node resection may not be needed for patients with cervical cancer, especially in the early stage, if the pre- or intraoperative diagnosis of lymph node status is correct. The aim of this study was to evaluate the diagnostic accuracy of pelvic lymph node metastasis for fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) and sentinel node biopsy (SNB) of cervical cancer patients.Forty-eight patients with cervical cancer were imaged with FDG PET/CT before radical hysterectomy and underwent an SNB followed by systematic pelvic lymph node dissection. The diagnostic accuracy for predicting pelvic node metastases for FDG PET/CT and SNB compared with the ultimate histologic status was analyzed.Among 96 hemi-pelvises (HPs) in 48 patients, pelvic lymph node metastases were obtained in 12 HPs. The sensitivity of pelvic node metastases for FDG PET/CT and SNB was 8.3% and 75.0%, respectively. The specificity for FDG PET/CT and SNB was 97.6% and 94.0%, respectively. The negative predictive value for FDG-PET/CT and SNB was 88.2% and 100%, respectively.SNB is more suitable for detecting pelvic node metastases than FDG PET/CT. The omission of systematic pelvic lymphadenectomy should be considered based on the findings of SNB, not FDG PET/CT.