An Overview of Endometrial Cancer

Christian Marth, MD, PhD, discusses the prevalence of endometrial cancer, as well as the steps that lead to diagnosis.


Bradley J. Monk, MD, FACS, FACOG: Hello, and welcome to this OncLive®Insights Program. My name is Bradley [Brad] Monk. I’m a gynecologic oncologist from Phoenix, Arizona, and this is “Treatments for Advanced or Recurrent Endometrial Cancer: Chemotherapy and Beyond.” We’re so excited to be here. The evolution of endometrial cancer treatment and biomarker assessment is rapidly evolving. I hope you enjoy this program. I’m joined by my friend and colleague, Christian Marth.

Christian Marth, MD, PhD: It’s a great pleasure for me to be here today. I am a gynecologic oncologist from the [Innsbruck] Medical University in Innsbruck in Austria, and we are good friends and [have been] working together for years, so it’s a very good possibility now to exchange our experiences in this disease.

Bradley J. Monk, MD, FACS, FACOG: Thank you for being here. I know you’re so busy and it’s Professor Marth, to most people, but he’s my Christian. So I’m going to call him Christian. He’s going to call me Brad. So, thank you. Let’s get into it. I want to talk about what endometrial cancer is. You could even refer to it as uterine cancer. I get it that the cervix is part of the uterus, but uterine cancer generally is the uterine corpus or endometrial cancer. What is endometrial cancer and what biomarkers do you assess?

Christian Marth, MD, PhD: Endometrial cancer is the most common gynecologic cancer. In the US you expect more than 60,000 cases a year, and the incidence is rising and even the mortality is rising. So that’s a great unmet medical need to improve the diagnosis and treatment of this disease. The disease appears mostly postmenopausal in women with obesity, hypertension, and diabetes and usually occurs with bleeding as the first symptom, [that is] how we diagnose the disease. We are doing a D&C [dilation and curettage], and we are doing a hysteroscopy. We are collecting the material, and this is the start.

Initially, we had only the microscope to look there to say, “Oh, that’s endometrial carcinoma.” We’re distinguishing some groups, Type 1 and Type 2, but this is historical now. We have The Cancer Genome Atlas data. We have a lot of evolution there. And now we know that we have to do a molecular analysis of the tumor specimen, and it has to be done at the initial probe to understand the risk of this disease and the factors driving endometrial carcinoma. We know and distinguish now 4 groups. We have the POLE [polymerase epsilon] hypermutated tumors, which have a lot of mutations, millions of mutations in the genome. This is a tumor with a very good prognosis probably because they have a lot of new antigens and the natural immunotherapy by the blood itself is able to control the disease. We have the mismatch repair deficient disease, which again, is also driven by DNA repair defect. And these have an intermediate prognosis, also with many mutations. Then we have the p53 abnormal, the p53 mutated tumors, and those with a very poor prognosis with fewer other mutations, normally driven by copy number alterations. And then we have a group, the NSMP, the non-specific molecular profile. That’s a very heterogeneous group where we really don’t know what the different types are there. So there’s more analysis necessary.

To characterize those tumors we need to know those markers. First, you have to do a mismatch repair IHC [immunohistochemistry screening] for proteins. You can do immunohistochemistry for p53 abnormality. You should do a POLE mutational analysis for next genome sequencing, for example. And for the NSMP, it’s important to have the hormone receptor analysis performed. You can do additional markers. We, for example, are always also looking for HER2 expression.

Bradley J. Monk, MD, FACS, FACOG: I think the good news is that all of those, but POLE or immunohistochemistry, can be done locally at the lab, locally at the hospital. I think the other point is that although he lives in Innsbruck in Europe and I live in Arizona in the US, it’s the same. Everything that you said, I’m not quite as smart as you, but I probably could have said something close to it, and that’s what we do. That’s what all my partners do. And frankly, if you’re not doing it, that’s what you should do. Again, dMMR [deficient mismatch repair], p53, evaluating the NSMP with ER [estrogen receptor] and also HER2, and if you have the capability, next-generation sequencing.

Now, p53 is a little tricky with the immunohistochemistry. If the mutation causes a backup of the protein, then it’s overexpressed so it’s technically mutated. If the mutation is early in the gene, it could be silenced. That’s p53. No, both are mutated. But the typical wild-type is sort of a modeled intermediate immunohistochemistry expression. So that’s interesting. We do the same things. Do you do endometrial biopsies in the office with a little plastic [Silastic catheter] or do you go to the OR [operating room]?

Christian Marth, MD, PhD: Normally we are going to the OR. A day [at the] hospital doing D&C and hysteroscopy.

Bradley J. Monk, MD, FACS, FACOG: We have this opportunity in the office to do an endometrial biopsy with a Silastic catheter, a 2.1 millimeter outer diameter. I’m sure you can do it. If it’s negative though, it doesn’t mean that there’s no cancer. So you can’t say, “Oh, she’s bleeding, let’s just ignore it because the endometrial biopsy is negative.” You have to pursue it. The other thing that you said is that most of these patients have bleeding. So we need your help to get that message out there that once a woman has gone through menopause, any brown discharge, any spot, we have to spot the spot. There’s a campaign actually to diagnose it early, so that’s great.

Transcript edited for clarity.

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