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Simple test could lead to more personalised treatment of rare ovarian cancer

Embargoed until: Publicly released:
Peer-reviewed: This work was reviewed and scrutinised by relevant independent experts.

Experimental study: At least one thing in the experiment was changed to see if it had an impact on the subjects (often people or animals) – eg: changing the amount of time mice spend on an exercise wheel to find out what impact it has on weight loss.

People: This is a study based on research using people.

Cells: This is a study based on research in micro-organisms, cells, tissue, organs or non-human embryos.

Observing how cells are organised in mucinous ovarian cancer can lead to new treatment options, study shows. By looking down a microscope for two different ‘patterns of invasion’ – the way that cancer cells invade ovarian tissue – oncologists can better predict which patients may have better or worse prognoses and can target treatment accordingly.

Journal/conference: Clinical Cancer Research

Link to research (DOI): 10.1158/1078-0432.CCR-22-1206

Organisation/s: The University of New South Wales

Funder: We are grateful for financial support for this study from UNSW Faculty of Medicine and Health. Funding for this study came from Michael L Friedlander NHMRC program grant APP1092856, and the accelerator grant of NSW Health PhD Scholarship Program awarded to Nicola S Meagher. Funding for individual studies AOCS: The Australian Ovarian Cancer Study was supported by the U.S. Army Medical Research and Materiel Command under DAMD17‐01‐1‐0729, The Cancer Council Victoria, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Foundation of Western Australia (Multi-State Applications 191, 211, and 182), The Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; ID199600; ID400413 and ID400281); AOV: Canadian Institutes of Health Research (MOP‐86727).; BAV: ELAN Funds of the University of Erlangen‐Nuremberg; DOV: NCI/NIH R01CA168758, NCI/NIH R01CA112523 and NCI/NIH R01CA087538; HSA: The Health Science Alliance (HSA) Biobank acknowledges financial support from the Translational Cancer Research Network, funded by the Cancer Institute NSW. KRA: This study was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 0920010); POC: POC study was supported by the program of the Minister of Science and Higher Education under the name "Regional Initiative of Excellence" in 2019-2022 project number 002 / RID / 2018/19 amount of financing 12 000 000 PLN; PRM: The University of Pittsburgh School of Medicine Dean’s Faculty Advancement Award (Modugno) provided support for this research. Funding was also provided by the National Science Foundation (DGE-2217399-Modugno). The views expressed are those of the authors and do not necessarily reflect the views of the National Science Foundation. This project used the UPMC Hillman Cancer Center and Tissue and Research Pathology/Pitt Biospecimen Core shared resource which is supported in part by National Cancer Institute award P30CA047904; SEA: Cancer Research UK C490/A16561, the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Cambridge Cancer Centre. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. VAN: BC’s Gynecological Cancer Research Team (OVCARE) receives core funding from The BC Cancer Foundation and the VGH and UBC Hospital Foundation; WMH: National Health and Medical Research Council of Australia, Enabling Grants ID 310670 and ID 628903. Cancer Institute NSW Grants 12/RIG/1‐17 and 15/RIG/1‐16. The Westmead GynBiobank acknowledges financial support from the Sydney West Translational Cancer Research Centre, funded by the Cancer Institute NSW. VIP: The Variants in Practice study was supported by the National Health and Medical Research Council of Australia (NHMRC; APP1023698; 1092856). NSM is supported by the NSW Ministry of Health and UNSW Sydney under the NSW Health PhD Scholarship Program, and the Translational Cancer Research Network. KLG supported by US Dept of Defense (OC170121), Australian National Health and Medical Research Council and the Peter MacCallum Cancer Foundation. SJR is supported by National Health and Medical Research Council of Australia (NHMRC) grant APP2009840. DDLB is supported by the National Health and Medical Research Council of Australia (NHMRC Fellowship (APP1117044) and Program Grant APP1092856) and the United States Department of Defence (DoD) Ovarian Cancer Transitional Leverage Award (W81XWH‐12‐1‐0104); MK received support through the Calgary Laboratory Services research support fund (RS19-612). AB received support through the Ovarian Cancer Research Fund (OCRF). JDB acknowledges funding and support from Cancer Research UK (grant numbers A22905, A15601 and A17197). MA is funded through a Michael Smith Foundation for Health Research Scholar Award and the Janet D. Cottrelle Foundation Scholars programme managed by the BC Cancer Foundation. DGH receives support from the Dr. Chew Wei Memorial Professorship in Gynecologic Oncology and the Canada Research Chairs programme (Research Chair in Molecular and Genomic Pathology). ADeF. was funded by Cancer Institute NSW grant 15/TRC/1-01. BK is funded through an American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. KS received support from the Swedish Cancer Foundation (CAN 18-384) and the Swedish state under the agreement between the Swedish government and the county council (ALFGBG-965552). The contents of the published material are solely the responsibility of the authors and do not reflect the views of NHMRC.

Media release

From: The University of New South Wales

A global study into mucinous ovarian cancer could help oncologists recommend the best treatment for women who are diagnosed early with the condition.

By looking down a microscope for two different ‘patterns of invasion’ – the way that cancer cells invade ovarian tissue – oncologists can better predict which patients may have better or worse prognoses and can target treatment accordingly. The finding was reported in a paper published today in Clinical Cancer Research, a journal of the American Association for Cancer Research.

“Mucinous ovarian cancer is a rare type of ovarian cancer. It actually has more in common with gastrointestinal cancers, and can be hard to diagnose and hard to treat once it has spread beyond the ovaries,” says lead author Nicki Meagher, who has just completed her PhD in the Molecular Oncology group, UNSW School of Clinical Medicine.

She says that observing which of the two types of invasion patterns that the cancer cells form could help specialists decide on treatment strategies.

“We’ve shown for the first time that women who have early-stage disease – meaning they have tumours that haven't spread beyond the ovary – have much poorer survival chances in the first two years from diagnosis if they have what we call an infiltrative pattern of invasion.

“Knowing this in the early stage of the disease means we can identify patients who could benefit from additional chemotherapy following surgery to remove their ovaries.”

The two patterns of invasion are defined by the way the cancer cells organise themselves when viewed under a microscope. The infiltrative pattern of invasion associated with poorer health outcomes shows cancer cells spreading in an uneven, haphazard way through the ovarian tissue. The other pattern is known as expansile, where cells expand through tissue in a more orderly manner, and is associated with better prognoses.

Up until now, other studies had suggested that the infiltrative pattern of invasion was associated with poorer patient outcomes, but no study had large enough numbers of patients with early-stage cancer to reach statistical significance.

But the current study, that involved more than 100 researchers in Australia, UK, Canada, Asia, Europe and the US, was able to test this hypothesis in much larger numbers by examining the tissue of 604 patients. The researchers also looked for the expression of 19 genes including THBS2 and TAGLN in addition to the patterns of invasion.

Professor Susan Ramus who oversaw the global study and heads the Ovarian Tumour Tissue Analysis consortium says that guidelines on how to treat women with early-stage mucinous ovarian cancer have differed around the world due to limited data on infiltrative patterns of invasion associated with survival rates.

“For example, in some parts of the world, an infiltrative pattern was acknowledged as an important feature and determined what treatment those women receive,” Professor Ramus says.

“Whereas in others, all patients are recommended for the same pathway of treatment. We hope that after this large study treatment guidelines can be aligned and that we can target treatment for women who may have these more serious indicators, even if they are diagnosed in early stages.”

The researchers also noted that women with higher expression of two genes, THBS2 and TAGLN in their tumours, had poorer overall survival.

“We’re hoping that this may be able to help explain some of the biology potentially down the track,” says Ms Meagher.

“Another avenue could be that knowledge of expression of these genes could assist in developing targeted drugs.”

The researchers are part of a wide network of experts who plan to carry out a validation study to further investigate these genomic markers as the basis for a targeted treatment strategy.

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