bims-ovdlit 2024-07-07 papers

Issue of 2024‒07‒07
three papers selected by
Lara Paracchini, Humanitas Research

J Pathol. 2024 Jul 02.

The genomic trajectory of ovarian high-grade serous carcinoma can be observed in STIC lesions.

Zhao Cheng, Darren P Ennis, Bingxin Lu, Hasan B Mirza, Chishimba Sokota, Baljeet Kaur, Naveena Singh, Olivia Le Saux, Giorgia Russo, Gaia Giannone, Laura A Tookman, Jonathan Krell, Chris Barnes, Jackie McDermott, Iain A McNeish.

Ovarian high-grade serous carcinoma (HGSC) originates in the fallopian tube, with secretory cells carrying a TP53 mutation, known as p53 signatures, identified as potential precursors. p53 signatures evolve into serous tubal intraepithelial carcinoma (STIC) lesions, which in turn progress into invasive HGSC, which readily spreads to the ovary and disseminates around the peritoneal cavity. We recently investigated the genomic landscape of early- and late-stage HGSC and found higher ploidy in late-stage (median 3.1) than early-stage (median 2.0) samples. Here, to explore whether the high ploidy and possible whole-genome duplication (WGD) observed in late-stage disease were determined early in the evolution of HGSC, we analysed archival formalin-fixed paraffin-embedded (FFPE) samples from five HGSC patients. p53 signatures and STIC lesions were laser-capture microdissected and sequenced using shallow whole-genome sequencing (sWGS), while invasive ovarian/fallopian tube and metastatic carcinoma samples underwent macrodissection and were profiled using both sWGS and targeted next-generation sequencing. Results showed highly similar patterns of global copy number change between STIC lesions and invasive carcinoma samples within each patient. Ploidy changes were evident in STIC lesions, but not p53 signatures, and there was a strong correlation between ploidy in STIC lesions and invasive ovarian/fallopian tube and metastatic samples in each patient. The reconstruction of sample phylogeny for each patient from relative copy number indicated that high ploidy, when present, occurred early in the evolution of HGSC, which was further validated by copy number signatures in ovarian and metastatic tumours. These findings suggest that aberrant ploidy, suggestive of WGD, arises early in HGSC and is detected in STIC lesions, implying that the trajectory of HGSC may be determined at the earliest stages of tumour development. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Keywords: STIC; evolution; high‐grade serous carcinoma; whole‐genome duplication

DOI: https://doi.org/10.1002/path.6322

J Natl Cancer Inst. 2024 Jul 04. pii: djae164. [Epub ahead of print]

Ovarian cancer risk factors in relation to family history.

Guoqiao Zheng, Louise Baandrup, Jiangrong Wang, Rasmus Hertzum-Larsen, Charlotte Gerd Hannibal, Mette Tuxen Faber, Karin Sundström, Susanne K Kjær.

BACKGROUND: Women with a family history of breast and/or ovarian cancer have an increased ovarian cancer risk. Yet it remains uncertain if common ovarian cancer risk factors-especially those which are modifiable-affect this high-risk population similarly to the general population.METHODS: Using the Danish and Swedish nationwide registers, we established two nested case-control study populations in women with a family history of breast and/or ovarian cancer (2,138 ovarian cancers, 85,240 controls) and women without (10,730 ovarian cancers, 429,200 controls). The overall and histology-specific associations were assessed with conditional logistic regression. The country-specific estimates were combined based on a fixed-effect assumption.
RESULTS: Multiparity, hysterectomy, tubal ligation, salpingectomy, and oral contraceptive (OC) use were associated with a reduced risk of ovarian cancer in both women with and without a family history, while endometriosis and menopausal hormone treatment (MHT) were associated with increased risk. Multiparity and OC use presented protective effects across all histologic subtypes except mucinous ovarian cancer which was not associated with OC use. MHT increased the risk of serous ovarian cancer but decreased the risk of the mucinous and clear cell cancers. Endometriosis was especially related to an increased risk of endometrioid and clear cell ovarian cancer.
CONCLUSION: Factors associated with a decreased ovarian cancer risk were similar between women with and without a family history of breast and/or ovarian cancer. Given the higher baseline risk for women with a family history, special attention should be paid to risk factors like endometriosis and nulliparity in this high-risk population.

DOI: https://doi.org/10.1093/jnci/djae164