Human Uterine Biopsy: Research Value and Common Pitfalls.

The human uterus consists of the inner endometrium, the myometrium, and the outer serosa. Knowledge of the function of the uterus in health and disease is relevant to reproduction, fertility, embryology, gynaecology, endocrinology, and oncology. Research performed on uterine biopsies is essential to further the current understanding of human uterine biology. This brief review explores the value of the uterine biopsy in gynaecological and human fertility research and explores the common problems encountered when analysing data generated from different types of uterine biopsies, with the aim of improving the quality, reproducibility, and clinical translatability of future research

Developing a Preoperative Algorithm for the Diagnosis of Uterine Leiomyosarcoma

Early diagnosis of the rare and life-threatening uterine leiomyosarcoma (LMS) is essential for prompt treatment, to improve survival. Preoperative distinction of LMS from benign leiomyoma remains a challenge, and thus LMS is often diagnosed post-operatively. This retrospective observational study evaluated the predictive diagnostic utility of 32 preoperative variables in 190 women who underwent a hysterectomy, with a postoperative diagnosis of leiomyoma (n = 159) or LMS (n = 31), at the Liverpool Women’s National Health Service (NHS) Foundation Trust, between 2010 and 2019. A total of 7 preoperative variables were associated with increased odds of LMS, including postmenopausal status (p < 0.001, OR 3.08), symptoms of pressure (p = 0.002, OR 2.7), postmenopausal bleeding (p = 0.001, OR 5.01), neutrophil count ≥7.5 × 109/L (p < 0.001, OR 5.72), haemoglobin level <118 g/L (p = 0.037, OR 2.22), endometrial biopsy results of cellular atypia or neoplasia (p = 0.001, OR 9.6), and a mass size of ≥10 cm on radiological imaging (p < 0.0001, OR 8.52). This study has identified readily available and easily identifiable preoperative clinical variables that can be implemented into clinical practice to discern those with high risk of LMS, for further specialist investigations in women presenting with symptoms of leiomyoma

Enriching Personalized Endometrial Cancer Research with the Harmonization of Biobanking Standards

Endometrial cancer is the commonest gynecological cancer, with an incidence predicted to escalate by a further 50&ndash;100% before 2025, due to the rapid rise in risk factors such as obesity and increased life expectancy. Endometrial cancer associated mortality is also rising, depicting the need for translatable research to improve our understanding of the disease. Rapid translation of scientific discoveries will facilitate the development of new diagnostic, prognostic and therapeutic strategies. Biobanks play a vital role in providing biospecimens with accompanying clinical data for personalized translational research. Wide variation in collection, and pre-analytic variations in processing and storage of bio-specimens result in divergent and irreproducible data from multiple studies that are unsuitable for collation to formulate robust conclusions. Harmonization of biobanking standards is thus vital, in facilitating international multi-center collaborative studies with valuable outcomes to improve personalized treatments. This review will detail the pitfalls in the biobanking of biosamples from women with cancer in general, and describe the recent international harmonization project that developed standardized research tools to overcome these challenges and to enhance endometrial cancer research, which will facilitate future development of personalized novel diagnostic strategies and treatments

Human Endometrial Carcinogenesis Is Associated with Significant Reduction in Long Non-Coding RNA, TERRA

Telomeres are transcribed as long non-coding RNAs called TERRAs (Telomeric repeat containing RNA) that participate in a variety of cellular regulatory functions. High telomerase activity (TA) is associated with endometrial cancer (EC). This study aimed to examine the levels of three TERRAs, transcribed at chromosomes 1q-2q-4q-10q-13q-22q, 16p and 20q in healthy (n = 23) and pathological (n = 24) human endometrium and to examine their association with cellular proliferation, TA and telomere lengths. EC samples demonstrated significantly reduced levels of TERRAs for Chromosome 16p (Ch-16p) (p < 0.002) and Chromosome 20q (Ch-20q) (p = 0.0006), when compared with the postmenopausal samples. No significant correlation was found between TERRA levels and TA but both Ch-16p and Ch-20q TERRA levels negatively correlated with the proliferative marker Ki67 (r = −0.35, p = 0.03 and r = −0.42, p = 0.01 respectively). Evaluation of single telomere length analysis (STELA) at XpYp telomeres demonstrated a significant shortening in EC samples when compared with healthy tissues (p = 0.002). We detected TERRAs in healthy human endometrium and observed altered individual TERRA-specific levels in malignant endometrium. The negative correlation of TERRAs with cellular proliferation along with their significant reduction in EC may suggest a role for TERRAs in carcinogenesis and thus future research should explore TERRAs as potential therapeutic targets in EC