Michael Anglesio. Photo courtesy of BC Cancer Agency
Genetic sequencing by scientists at UBC, the BC Cancer Agency and Vancouver Coastal Health has confirmed that tumours that arise simultaneously in the uterus and ovary are not a case of classic metastasis, and thus don’t warrant aggressive treatment with chemotherapy and radiation. The finding, published in the Journal of the National Cancer Institute (JNCI), substantiates the approach taken by doctors in B.C.
Known as synchronous endometrial and ovarian (SEO) cancer, tumours on the endometrial lining of the uterus appear simultaneously with tumours on the ovary, and vice versa. Synchronous endometrial and ovarian cancers have been reported in five to 10 per cent of endometrial or ovarian cancers.
Metastasis, the spread of a tumour from one organ to another, is virtually always an indication of an advanced stage cancer that requires aggressive treatment with chemotherapy and/or radiation therapy. However, SEO tumours behave as if they are independent, localized early-stage tumours that often respond well to surgery alone. This controversy regarding whether SEO cancer is metastatic has led to widely differing treatments.
By sequencing frequently mutated cancer genes in 18 pairs of SEO tumours, the scientists have provided definitive evidence that each pair of SEO tumours are in fact genetically related clones — an example of what the scientists call “pseudo-metastasis,” in which cancer likely spreads through the fallopian tube, not the blood stream. The ovary and uterus provide a unique environment where these cancers are initially constrained.
“Pseudo-metastasis is still something of a mystery,” says lead author Michael Anglesio, Research Associate in the Department of Molecular Oncology at the BC Cancer Agency. “Whether the initial event takes place in the ovary or the endometrium, and what keeps cells temporarily restricted to these special organs without metastasizing to the rest of the body, are things that we are now researching.”
Pseudo-metastasis has important implications for treatment. In B.C., SEO cancer patients have generally been treated conservatively by surgically removing the tumours. On a global scale, however, many women with SEO tumours have received more aggressive treatment designed to fight late-stage metastatic cancer — chemotherapy and/or radiation therapy, both of which carry more severe side-effects.
David Huntsman
“This research will have an immediate impact on the management of ovarian and endometrial cancers,” says senior author David Huntsman, Professor of Laboratory Medicine and Obstetrics and Gynaecology, the the Dr. Chew Wei Memorial Professor of Gynaecologic Oncology, and a Distinguished Scientist at the BC Cancer Agency. “It confirms that we’ve been taking the right approach to SEO cancers in British Columbia. This should influence treatment of the disease around the world so women do not undergo needlessly aggressive treatment.”
Meanwhile, a highly complementary study from New York’s Memorial Sloan Kettering Cancer Center, published in the same issue of JNCI, is giving both research teams overwhelming confidence in their findings.
“We are delighted that the findings of our studies are in agreement,” says Britta Weigelt, Assistant Member of the Department of Pathology at Memorial Sloan Kettering. “Together, these studies have resulted in a paradigm shift in the way SEO cancers are perceived. By bringing together pathology and genetics, we have solved a long standing biological question and clinical dilemma.”