bims-ovdlit 2023-03-26 papers

Issue of 2023–03–26
four papers selected by
Lara Paracchini, Humanitas Research

J Pathol Clin Res. 2023 Mar 22.

p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study.

AOCS Group

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.

Keywords: TP53; clear cell; endometrioid; high-grade serous carcinoma; ovarian cancer; p53; prognosis

DOI: https://doi.org/10.1002/cjp2.311

Int J Gynecol Cancer. 2023 Mar 23. pii: ijgc-2023-004464. [Epub ahead of print]

PARP inhibitor era: current status and future directions.

Robert L Coleman.

Keywords: Ovarian Cancer

DOI: https://doi.org/10.1136/ijgc-2023-004464

Gynecol Oncol Rep. 2023 Apr;46 101157

Prevention over screening for ovarian cancer in patients with high-risk germline mutations: Misinterpreting the findings of ALDO.

Beryl L Manning-Geist, Matthew Flint, Kara Long Roche.

In November 2022, the findings of the Avoiding Late Diagnosis of Ovarian cancer (ALDO) study were published. Subsequent media coverage suggested that investigators had found a safe alternative to risk-reducing bilateral salpingoophorectomy (rrBSO) in patients with pathogenic BRCA1 and BRCA2 germline mutations who chose to decline or defer risk-reducing surgery. Unfortunately, this media coverage was largely misleading. Specifically, in the ALDO trial, 4 of 6 patients found to have ovarian cancer by the ALDO screening methodology were diagnosed with advanced-stage disease. The primary endpoint of the ALDO study was the rate of complete surgical cytoreduction, rather than stage at diagnosis or overall survival, which is an inappropriate surrogate for benefit in a population at risk of ovarian cancer. The ALDO trial again demonstrates that screening women at high-risk of ovarian cancer should not be considered a safe alternative to risk-reducing surgery, and can lead to false reassurance and the development of preventable cases of ovarian cancer. While we should continue to investigate new screening options, future efforts should largely focus on why patients decline rrBSO in the first place and how we can pivot our efforts to better address concerns related to rrBSO, including sequelae of surgical menopause. Furthermore, as we continue to understand the role of the fallopian tube in the epithelial ovarian cancer (EOC) disease process, we must identify the role of salpingectomy alone in prevention of EOC.

DOI: https://doi.org/10.1016/j.gore.2023.101157

Eur J Obstet Gynecol Reprod Biol. 2023 Mar 20. pii: S0301-2115(23)00105-7. [Epub ahead of print]

Intraoperative rupture and chemotherapy use in stage I ovarian cancer.

Koji Matsuo, Alesandra R Rau, Hiroko Machida, Lynda D Roman, Jason D Wright.

Keywords: Chemotherapy; Histology; Intraoperative capsule rupture; Ovarian cancer; Stage I; Upstage

DOI: https://doi.org/10.1016/j.ejogrb.2023.03.015