Infiltrative pattern of invasion is independently associated with shorter survival and desmoplastic stroma markers FAP and THBS2 in mucinous ovarian carcinoma.

AIMS: Mucinous ovarian carcinoma (MOC) is a rare ovarian cancer histotype with generally good prognosis when diagnosed at an early stage. However, MOC with the infiltrative pattern of invasion has a worse prognosis, although to date studies have not been large enough to control for covariables. Data on reproducibility of classifying the invasion pattern are limited, as are molecular correlates for infiltrative invasion. We hypothesized that the invasion pattern would be associated with an aberrant tumour microenvironment. METHODS AND RESULTS: Four subspecialty pathologists assessed interobserver reproducibility of the pattern of invasion in 134 MOC. Immunohistochemistry on fibroblast activation protein (FAP) and THBS2 was performed on 98 cases. Association with survival was tested using Cox regression. The average interobserver agreement for the infiltrative pattern was moderate (kappa 0.60, agreement 86.3%). After reproducibility review, 24/134 MOC (18%) were determined to have the infiltrative pattern and this was associated with a higher risk of death, independent of FIGO stage, grade, and patient age in a time-dependent manner (hazard ratio [HR] = 10.2, 95% confidence interval [CI] 3.0-34.5). High stromal expression of FAP and THBS2 was more common in infiltrative MOC (FAP: 60%, THBS2: 58%, both P < 0.001) and associated with survival (multivariate HR for FAP: 1.5 [95% CI 1.1-2.1] and THBS2: 1.91 [95% CI 1.1-3.2]). CONCLUSIONS: The pattern of invasion should be included in reporting for MOC due to the strong prognostic implications. We highlight the histological features that should be considered to improve reproducibility. FAP and THBS2 are associated with infiltrative invasion in MOC.

POLE-mutated Endometrial "Carcinosarcoma".

The molecular subtype classification of endometrial carcinomas has conceptually changed our approach to this disease. However, open questions remain about how to integrate certain histotype diagnoses with the molecular subtype. We report 2 cases with morphologic suspicion for endometrial carcinosarcoma, that still fell short of the essential criteria for diagnosing carcinosarcoma. On subsequent molecular testing pathogenic POLE mutations were detected and a descriptive diagnosis of endometrial endometrioid carcinomas, low-grade with a homologous sarcoma component was rendered. This challenges the existence of POLE-mutated "carcinosarcoma."

Narrative review on the evolving role of HER2/neu targeting in uterine serous cancers.

Background and Objective: Serous endometrial cancers (ECs) are an aggressive histotype of ECs which are disproportionately responsible for 40% of cancer-specific mortality rates despite constituting only 5-10% of all uterine cancers in incidence. In recent times, it has become increasingly evident that about 20-40% of uterine serous cancers (USCs) have molecular alterations in ERBB2 pathway with human epidermal growth factor receptor 2 (HER2/neu) amplification or overexpression. We summarise the evidence on genetic and molecular alterations in HER2/neu pathway in USC with a focus on testing criteria, targeting agents and resistance mechanisms. Methods: We conducted a database search of PubMed/Medline up to 28th February 2023 for articles published in the English language using pre-defined search terms. One hundred and seventy-one relevant articles were subsequently reviewed for eligibility and inclusion in the review. Key Content and Findings: The Cancer Genome Atlas (TCGA) classification is a significant development in the molecular profiling of ECs with a positive impact on the treatment of these tumors including USCs. Testing criteria for HER2/neu in USC with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) has evolved in more than a decade with progress made towards EC specific testing guidelines. The findings of a recent phase III study have led to the development of practice changing guidelines towards improving patient outcomes. Conclusions: Molecular aberration in the HER2/neu pathway contributes to the aggressive behaviour of USC. Considering the clinical benefit conferred by HER2/neu targeted therapy, HER2/neu testing is recommended for all cases of serous EC in advanced and recurrent settings. Trastuzumab in combination with platinum and taxanes based chemotherapy is the recommended treatment option for patients with advanced or recurrent serous cancers who test positive to HER2/neu. Clinical trials on targeted therapy are ongoing and future research should focus on selection of patients who will derive the most benefit from such therapy.

Novel Strategy of Training the Accredited Social Health Activists via Application-Based Telemedicine for Cervical Cancer Screening by Human Papillomavirus Self-Sampling: The TRACK Study.

PURPOSE: This pilot study is aimed to analyze a novel strategy of cervical cancer screening by training of Accredited Social Health Activist (ASHA) workers via telemedicine to counsel women for human papillomavirus (HPV) self-sampling. MATERIALS AND METHODS: This is a pilot, community-based, prospective, single-arm study. Physicians trained the ASHA workers regarding self-sampled HPV testing via a mobile application and telephonically using videos and e-pamphlets, who in turn trained the clients in community. The HPV kits were transported via prepaid courier service. RESULTS: Four hundred and sixty-five women of age group 30-65 years were tested by 47 teletrained ASHA workers. The mean age of ASHA worker and clients was 39.47 ± 6.45 and 37.26 ± 8.38 years, respectively. Of the ASHA workers, 91.7% were satisfied with the information provided during telecounseling, 95.7% could understand the contents of mobile app easily, and 93.6% could fill the data of clients in app easily. Of the clients, 99.6% were satisfied with counseling by ASHA workers and 98% found it easy to self-sample. The acceptability of this strategy among clients was 58.2%. The feasibility of this strategy (percentage of clients who find it easy/those who did self-sampling) was around 99%. Among those screened, 11.8% were high-risk HPV-positive and 85.5% had follow-up at the study center. CONCLUSION: The current study highlights a novel strategy of cervical cancer screening by incorporating the role of telemedicine in training ASHA workers and their role in improving the screening by home-based delivery of HPV kits with promising results.

Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma.

PURPOSE: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC). EXPERIMENTAL DESIGN: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss. RESULTS: RB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1. CONCLUSIONS: Co-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.

Synoptic Operative Reporting in Cervical Cancer Surgeries: Experience From a Single Oncology Center.

Objective In today's era of highly methodological oncological practices in place, we have a huge database to regulate, and it is foreseeable that a humongous load of information is ahead of us that we need to organize and comprehend. With the advancement in surgical equipment and evolving procedures, we need to store the information in a transferrable, understandable, and systematic way to prevent any ebb in the future. The systematic recording of operative data is even more important for patient management, training, and research. Standardized reporting also helps surgical residents have a better understanding of all aspects of the procedure. This study aims to analyze the synoptic operative reporting in cervical cancer patients from December 2009 to February 2020 in a single tertiary care center dedicated to providing oncology services to patients. This study will analyze the understandability, volume, and ease of transference of data during the given time period. Methodology The Alberta Cancer Registry was contacted to obtain data from the synoptic operative reports. Synoptic Operative Reports of all the patients operated on cervical cancer from December 2009 to February 2020. Results The data were obtained for 574 patients. As many as 463 patients were operated on for stage 1 and 2 cervical cancers and 10 patients for advanced and recurrent cervical cancer. A total of 101 patients were operated on for high-grade cervical dysplasia (HSIL). Adenocarcinoma was the most common histology. Laparotomy was performed in 308 patients, whereas others had laparoscopic procedures. Details of the surgery from the beginning of the incision to closure were recorded. The cervical cancer template consisted of 356 questions. There were separate templates for advanced and early-stage cancer. However, even with the meticulously detailed report, an average of only eight minutes was taken by each user to complete the template. Conclusion The computerized synoptic operative report has an upper hand over the dictated documentation report along with the ease of execution without missing essential substance. Its utility as an educational tool is very promising. Therefore, we encourage other facilities, especially cancer centers, to use synoptic operative reports more extensively not only for cervical cancer surgeries but also for other ones.