Hereditary Breast and Ovarian Cancers Meeting 2011, New York, USA
Cell of origin of ovarian cancer
Professor Louis Dubeau – University of Southern California, Los Angeles, USA
I talk about the issues related to the site of origin of ovarian cancer, so it’s intriguing that there is a huge effort focussed on the early detection of ovarian cancer. Women who have high genetic risk of ovarian cancer have risk reducing surgery, some of the organs are removed to protect them against the possibility of developing ovarian cancer and all this is done in spite of the fact that we cannot agree where the tumours actually come from. So obviously there’s a problem in addressing those issues.
It used to be taught that ovarian cancer arises from the cells lining the ovarian surface, this is a theory that was developed in the early twentieth century and there was evidence for this then. But I think the current evidence argues that this is probably not the case. So I presented today some arguments about alternative theories. I think that what we’ve been referring to as ovarian cancer actually usually arises outside the ovaries so the term ovarian cancer is actually a misnomer. What’s been intriguing about ovarian cancer is that the way those tumours look, they are morphologically and functionally identical to tumours that arise in other sites of the reproductive tract. So the most common sub-type of ovarian cancer is called a serous sub-type. These tumours are morphologically identical to tumours that arise from the fallopian tube. And then we have the mucinous sub-type that resembles tumours from the endocervix and the endometrial that resembles tumours of the endometrium. And what’s intriguing is that there are no normal cells that we know of in a normal ovary that resemble any of those tissues. Not only this is the case, but the development of the ovary, going back to embryology, is totally unrelated to the development of the rest of the organs of the reproductive tract, including the fallopian tube, uterus and the endocervix. So I’ve been arguing that those tumours actually do originate from structures that have the same embryological derivation as those other organs and, without going into the details, what I presented today was evidence for this theory, based partly on mouse models with the reporter genes and other observations that ovarian tumours actually come from those structures that are embryologically related to the development of that part of the reproductive tract. The other point is that if ovarian tumours do not arise, or if most of them do not arise from the ovary, then we’ve not been calling them the right way. So I think it makes sense that we should change the terminology, we should not call them ovarian cancer any more.
I concluded the talk by making a suggestion about what the terminology should be. The term that I suggested is related to the embryological origin of the tissues. So we believe that ovarian tumours are derived from an embryological structure that we call the Müllerian ducts, so the terminology that we suggested were extra-uterine Müllerian carcinomas that can be subdivided into serous, mucinous, endometrial and clear cell, the same major sub-types that we’ve been referring to in calling them ovarian tumours.
Why is this classification important?
It’s very confusing to call something ovarian tumours and make up origins and try to explain that even if this is what they’re called, the tumours really are not coming from the ovary. I review grant applications of scientists, they’re writing applications on ovarian tumours and it’s not easy to explain to a review panel that ovarian tumours actually do not arise from the ovary. Plus, if the terminology is more accurate and pointing to what the actual site of origin is, there’s a huge effort directed at early detections, if we use a proper terminology then that would help people looking for precursor lesions and developing strategies to detect small tumours in those areas. The current technology distinguishes between three entities actually – ovarian carcinoma, fallopian tube carcinoma and primary peritoneal carcinomas. These are currently regarded as three separate entities which we believe are really the same, they all share a similar origin. So if the terminology that we use reflected that then it would facilitate designing clinical trials, for example currently clinical trials involving those tumours usually list all those three different sub-types and people don’t know how to… it complicates writing clinical trials if we need to include three different sub-types when we really need to include a single one.
