Changes in the tumour microenvironment mark the transition from serous borderline tumour to low-grade serous carcinoma.

Low-grade serous ovarian carcinoma (LGSC) is a rare and lethal subtype of ovarian cancer. LGSC is pathologically, biologically, and clinically distinct from the more common high-grade serous ovarian carcinoma (HGSC). LGSC arises from serous borderline ovarian tumours (SBTs). The mechanism of transformation for SBTs to LGSC remains poorly understood. To better understand the biology of LGSC, we performed whole proteome profiling of formalin-fixed, paraffin-embedded tissue blocks of LGSC (n = 11), HGSC (n = 19), and SBTs (n = 26). We identified that the whole proteome is able to distinguish between histotypes of the ovarian epithelial tumours. Proteins associated with the tumour microenvironment were differentially expressed between LGSC and SBTs. Fibroblast activation protein (FAP), a protein expressed in cancer-associated fibroblasts, is the most differentially abundant protein in LGSC compared with SBT. Multiplex immunohistochemistry (IHC) for immune markers (CD20, CD79a, CD3, CD8, and CD68) was performed to determine the presence of B cells, T cells, and macrophages. The LGSC FAP+ stroma was associated with greater abundance of Tregs and M2 macrophages, features not present in SBTs. Our proteomics cohort reveals that there are changes in the tumour microenvironment in LGSC compared with its putative precursor lesion, SBT. These changes suggest that the tumour microenvironment provides a supportive environment for LGSC tumourigenesis and progression. Thus, targeting the tumour microenvironment of LGSC may be a viable therapeutic strategy. © 2024 The Pathological Society of Great Britain and Ireland.

The Prevalence, Indications, Outcomes of the Most Common Major Gynecological Surgeries in Kazakhstan and Recommendations for Potential Improvements into Public Health and Clinical Practice: Analysis of the National Electronic Healthcare System (2014-2019).

OBJECTIVES: Major gynecological surgeries are indicated for the treatment of female genital pathologies. It is key to examine trends in gynecologic surgical procedures and updated recommendations by international gynecological societies to find opportunities for improvement of local guidelines. To date, a very limited number of reports have been published on the epidemiology of gynecological surgeries in Kazakhstan. Moreover, some local guidelines for gynecological conditions do not comply with the international recommendations. Thus, this study aims to investigate the prevalence, indications, and outcomes of the most common major gynecological surgeries by analyzing large-scale Kazakhstani healthcare data, and identifying possible opportunities for improvement of the local public health and clinical practice. METHODS: A descriptive, population-based study among women who underwent a gynecological surgery in healthcare settings across the Republic of Kazakhstan during the period of 2014-2019 was performed. Data were collected from the Unified Nationwide Electronic Health System (UNEHS). RESULTS: In total, 80,401 surgery cases were identified and analyzed in the UNEHS database for a period of 6 years (2014-2019). The median age of the participants was 40 years old, with 61.1% in reproductive age. The most prevalent intervention was a unilateral salpingectomy-29.4%, with 72.6% patients aged between 18-34 years. The proportion of different types of hysterectomies was 49.4%. In 20% of cases, subtotal abdominal hysterectomy was performed due to uterine leiomyoma. The proportion of laparoscopic procedures in Kazakhstani gynecological practice is as low-11.59%. CONCLUSIONS: The Kazakhstani public health and gynecological care sector should reinforce implementation of contemporary treatment methods and up-to-date policies and guidelines. The overall trends in surgical procedures performed for gynecological pathologies, including uterine leiomyoma and ectopic pregnancy treatment, should be changed in favor of the minimally invasive methods in order to adopt a fertility-sparing approach.

Gynecologic Cancer Risk and Genetics: Informing an Ideal Model of Gynecologic Cancer Prevention.

Individuals with proven hereditary cancer syndrome (HCS) such as BRCA1 and BRCA2 have elevated rates of ovarian, breast, and other cancers. If these high-risk people can be identified before a cancer is diagnosed, risk-reducing interventions are highly effective and can be lifesaving. Despite this evidence, the vast majority of Canadians with HCS are unaware of their risk. In response to this unmet opportunity for prevention, the British Columbia Gynecologic Cancer Initiative convened a research summit "Gynecologic Cancer Prevention: Thinking Big, Thinking Differently" in Vancouver, Canada on 26 November 2021. The aim of the conference was to explore how hereditary cancer prevention via population-based genetic testing could decrease morbidity and mortality from gynecologic cancer. The summit invited local, national, and international experts to (1) discuss how genetic testing could be more broadly implemented in a Canadian system, (2) identify key research priorities in this topic and (3) outline the core essential elements required for such a program to be successful. This report summarizes the findings from this research summit, describes the current state of hereditary genetic programs in Canada, and outlines incremental steps that can be taken to improve prevention for high-risk Canadians now while developing an organized population-based hereditary cancer strategy.