bims-ovdlit 2021-12-12 papers

Issue of 2021–12–12
four papers selected by
Lara Paracchini, Humanitas Research

Menopause. 2021 Dec 06.

Factors affecting surgical decision-making in carriers of BRCA1/2 pathogenic variants undergoing risk-reducing surgery at a dedicated hereditary ovarian cancer clinic.

Michelle R Jacobson, Melissa Walker, Gabrielle E V Ene, Courtney Firestone, Marcus Q Bernardini, Lisa Allen, Ella Huszti, Mara Sobel.

OBJECTIVE: Women with germline BRCA1/2 pathogenic variants have a significantly elevated lifetime risk of ovarian and fallopian tube cancer. Bilateral salpingo-oophorectomy (RRSO) is associated with a 90% reduction in the development of tubal and ovarian cancer. At our tertiary hospital, we have a dedicated clinic where women predisposed to hereditary ovarian/tubal cancer receive counseling on reproduction, risk reduction, surgical prophylaxis, and menopausal aftercare. The objective of this study was to evaluate the choices that Canadian women with BRCA1/2 pathogenic variants make regarding ovarian cancer risk reduction within this highly specialized multidisciplinary clinic.
METHODS: This retrospective chart review included all women with confirmed BRCA1/2 mutations referred to the Familial Ovarian Cancer Clinic at Women's College Hospital, Toronto, Canada over a 45-month time period. Patient demographics, preoperative consultation notes and investigations, intraoperative findings, and pathology were recorded.
RESULTS: A total of 191 women were included in our cohort; 140 (73.3%) underwent risk-reducing surgery and 51 (26.7%) deferred or declined surgery. In women who underwent surgical prevention (median age 45 [30-72] y), 123 (87.9%) underwent RRSO and 17 (12.1%) chose a risk-reducing bilateral salpingectomy with deferred oophorectomy. Of the women undergoing RRSO, 11 (8.9%) women chose concurrent hysterectomy. Prevalent themes affecting decision-making included fears around premature surgical menopause, family planning, and concerns around development of endometrial cancer related to tamoxifen.
CONCLUSION: Women with BRCA1/2 pathogenic variants face challenging decisions regarding risk reduction and care providers must be knowledgeable and supportive in helping women make informed and individualized choices about their care.
Video Summary:http://links.lww.com/MENO/A857.

DOI: https://doi.org/10.1097/GME.0000000000001900

Nat Rev Genet. 2021 Dec 08.

Computational analysis of cancer genome sequencing data.

Isidro Cortés-Ciriano, Doga C Gulhan, Jake June-Koo Lee, Giorgio E M Melloni, Peter J Park.

Distilling biologically meaningful information from cancer genome sequencing data requires comprehensive identification of somatic alterations using rigorous computational methods. As the amount and complexity of sequencing data have increased, so has the number of tools for analysing them. Here, we describe the main steps involved in the bioinformatic analysis of cancer genomes, review key algorithmic developments and highlight popular tools and emerging technologies. These tools include those that identify point mutations, copy number alterations, structural variations and mutational signatures in cancer genomes. We also discuss issues in experimental design, the strengths and limitations of sequencing modalities and methodological challenges for the future.

DOI: https://doi.org/10.1038/s41576-021-00431-y

J Histochem Cytochem. 2021 Dec 05. 221554211061359

Multi-modal Profiling of the Extracellular Matrix of Human Fallopian Tubes and Serous Tubal Intraepithelial Carcinomas.

Carine Renner, Clarissa Gomez, Mike R Visetsouk, Isra Taha, Aisha Khan, Stephanie M McGregor, Paul Weisman, Alexandra Naba, Kristyn S Masters, Pamela K Kreeger.

Recent evidence supports the fimbriae of the fallopian tube as one origin site for high-grade serous ovarian cancer (HGSOC). The progression of many solid tumors is accompanied by changes in the microenvironment, including alterations of the extracellular matrix (ECM). Therefore, we sought to determine the ECM composition of the benign fallopian tube and changes associated with serous tubal intraepithelial carcinomas (STICs), precursors of HGSOC. The ECM composition of benign human fallopian tube was first defined from a meta-analysis of published proteomic datasets that identified 190 ECM proteins. We then conducted de novo proteomics using ECM enrichment and identified 88 proteins, 7 of which were not identified in prior studies (COL2A1, COL4A5, COL16A1, elastin, LAMA5, annexin A2, and PAI1). To enable future in vitro studies, we investigated the levels and localization of ECM components included in tissue-engineered models (type I, III, and IV collagens, fibronectin, laminin, versican, perlecan, and hyaluronic acid) using multispectral immunohistochemical staining of fimbriae from patients with benign conditions or STICs. Quantification revealed an increase in stromal fibronectin and a decrease in epithelial versican in STICs. Our results provide an in-depth picture of the ECM in the benign fallopian tube and identified ECM changes that accompany STIC formation. (J Histochem Cytochem XX: XXX-XXX, XXXX).

Keywords: mass spectrometry; matrisome; multispectral immunohistochemistry; ovarian cancer; tumor microenvironment; tumor stroma

DOI: https://doi.org/10.1369/00221554211061359

BMJ. 2021 Dec 08. 375 e067528

Association of bilateral salpingo-oophorectomy with all cause and cause specific mortality: population based cohort study.

Maria C Cusimano, Maria Chiu, Sarah E Ferguson, Rahim Moineddin, Suriya Aktar, Ning Liu, Nancy N Baxter.

OBJECTIVES: To determine if bilateral salpingo-oophorectomy, compared with ovarian conservation, is associated with all cause or cause specific death in women undergoing hysterectomy for non-malignant disease, and to determine how this association varies with age at surgery.
DESIGN: Population based cohort study.
SETTING: Ontario, Canada from 1 January 1996 to 31 December 2015, and follow-up to 31 December 2017.
PARTICIPANTS: 200 549 women (aged 30-70 years) undergoing non-malignant hysterectomy, stratified into premenopausal (<45 years), menopausal transition (45-49 years), early menopausal (50-54 years), and late menopausal (≥55 years) groups according to age at surgery; median follow-up was 12 years (interquartile range 7-17).
EXPOSURES: Bilateral salpingo-oophorectomy versus ovarian conservation.
MAIN OUTCOMES MEASURES: The primary outcome was all cause death. Secondary outcomes were non-cancer and cancer death. Within each age group, overlap propensity score weighted survival models were used to examine the association between bilateral salpingo-oophorectomy and mortality outcomes, while adjusting for demographic characteristics, gynaecological conditions, and comorbidities. To account for comparisons in four age groups, P<0.0125 was considered statistically significant.
RESULTS: Bilateral salpingo-oophorectomy was performed in 19%, 41%, 69%, and 81% of women aged <45, 45-49, 50-54, and ≥55 years, respectively. The procedure was associated with increased rates of all cause death in women aged <45 years (hazard ratio 1.31, 95% confidence interval 1.18 to 1.45, P<0.001; number needed to harm 71 at 20 years) and 45-49 years (1.16, 1.04 to 1.30, P=0.007; 152 at 20 years), but not in women aged 50-54 years (0.83, 0.72 to 0.97, P=0.018) or ≥55 years (0.92, 0.82 to 1.03, P=0.16). Findings in women aged <50 years were driven largely by increased non-cancer death. In secondary analyses identifying a possible change in the association between bilateral salpingo-oophorectomy and all cause death with advancing age at surgery, the hazard ratio gradually decreased during the menopausal transition and remained around 1 at all ages thereafter.
CONCLUSION: In this observational study, bilateral salpingo-oophorectomy at non-malignant hysterectomy appeared to be associated with increased all cause mortality in women aged <50 years, but not in those aged ≥50 years. While caution is warranted when considering bilateral salpingo-oophorectomy in premenopausal women without indication, this strategy for ovarian cancer risk reduction does not appear to be detrimental to survival in postmenopausal women.

DOI: https://doi.org/10.1136/bmj-2021-067528