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Precursors to Prevention

In partnership with the VGH & UBC Hospital Foundation

In September 2010, OVCARE launched the world’s first ovarian cancer prevention campaign – the goal being to reduce the incidence of ovarian cancer by 40% over the next two decades.

OVCARE and other researchers have recently discovered that many of the high grade serous ovarian cancers originate in the distal fallopian tube and that most clear cell and endometrioid ovarian cancers arise from endometriosis.  A new initiative was launched to try and better understand what the earliest changes were in these cancers, and to develop tools to detect these lesions. We know the outcomes of women with early ovarian cancer is vastly improved over those women with advanced stage disease but as yet no screening or early detection strategies have proven effective. Through early detection, curative interventions can be undertaken preventing these early cancers (or precancers) from ever spreading.

The identification of precancerous lesions is fundamental in the understanding of how to prevent cancer, however, until a few years ago no precancerous lesion for ovarian cancer was known. It is now believed based on recent evidence by OVCARE researchers and others that the most common (70%) and lethal subtype of ovarian cancer, high-grade serous cancers, arise within the fallopian tube while clear cell carcinomas and endometrioid carcinomas, the 2nd and 3rd most common subtype accounting for about 25% of ovarian cancers, likely arise from endometriosis or endometriosis-like lesions. In the past, it was thought that endometriosis increased the risk of clear cell and endometrioid ovarian carcinomas, but no specific genetic links were known. Today, OVCARE is closer to finding the link thanks to the discovery by Dr. David Huntsman (OVCARE Scientific Director and genetic pathologist) of a gene mutation that is believed to be a precursor event in the transformation of endometriosis into cancer in about half of cancer cases.

As part of the PTP program, Dr. Jessica McAlpine (OVCARE clinician scientist and gynaecologic oncology surgeon) in collaboration with Drs. Pierre Lane, PhD (Research Scientist, BC Cancer Research Centre) and Calum MacAulay, PhD (Head of the Department of Integrative Oncology, BC Cancer Research Center) have successfully used optical imaging technologies to identify abnormal fallopian tube lesions ex vivo (early occult cancer and precancers). This technology may prove to be a step towards developing in vivo screening modalities for ovarian cancer, both in the general population and in women with inherited mutations with an associated increased risk of developing ovarian cancer. Although we have tools that can cannulate the narrow fallopian tubes, several challenges still exist in using autoflourescence as a screening tool in epithelial fallopian tube/ovarian cancers. The distal fallopian tubes have an extensive surface area with convoluted and mobile finger-like projections that are difficult both to screen entirely and to map in location if a lesion is identified in order to verify accuracy on final pathology. Regardless, the ability to identify these precursor or early occult lesions in fresh tissue ex vivo has proven invaluable as we are able to extract DNA and RNA for research purposes at a much higher quality than would be achievable in formalin-fixed paraffin embedded tissue. Lesions of interest are identified, genetic material is extracted, and next-generation sequencing performed to look for novel cancer-associated mutations. In this way we are learning more about the earliest changes in high grade serous ovarian cancers and how the genetic make-up differs from both normal tissues and advanced cancers.

Finally, OVCARE and the Department of Integrative Oncology at the BC Cancer Research Center are working to improve upon our current technique through development of optical molecular nanoprobes that would provide a second means to “highlight” abnormal regions.  An antibody which is in clinical use and identifies the protein p53 in tissue has been labeled with a fluorescent marker to create the molecular probe.  The first stage was to test this probe in human cell lines that either do or do not express the protein p53.  Studies indicate that the molecular probe is preferentially internalized by cells expressing the protein of interest.  The next stage of operations to test the molecular probe on ex vivo surgical specimens is ongoing.

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