Was your endometrial cancer tested for mutations in the gene POLE?

Posted by val64 @val64, Sep 3, 2022

I recently received the pathology results (Stage 1B Grade 3 endometriod carcinoma) on the specimens from my TH-BSO. I had thought that endometrial cancers like this would be routinely tested for mutations in a gene called POLE, which confers a better prognosis, but my sample was not. Apparently this is not part of the algorithm at the university hospital where I am being treated. They say they're working on offering this test, but that doesn't help me.

I have tried to ask my care team what my options are for getting this test done, but so far the only thing they mentioned is an extravagant sequencing test that isn't covered by insurance and seems to cost ~$6000. This is overkill, and way more than I would be willing to pay out of pocket.

Has anyone had POLE mutation testing done on their tumor specimen? If so, where where was this testing was performed? Did insurance cover it? How much did it cost?

Interested in more discussions like this? Go to the Gynecologic Cancers Support Group.

cls316 | @cls316 | Nov 12, 2022

In reply to @val64 "Many thanks for responding so quickly and for the info. Was this at Mayo? I'm interested..." + (show)

Hello NatureGirl15,
I am recently diagnosed with endometrial carcinoma 1B Grade 3. I had a total hysterectomy 2 weeks ago and await pelvic radiation therapy (28 doses).

Kindly post the link to the link to the NCCN Guidelines for endometrial carcinoma recommendation of molecular classification based on 3 tests. I would like to pursue this further with my physicians.

Wishing you all the very best.

Helen, Volunteer Mentor | @naturegirl5 | Nov 12, 2022

In reply to @cls316 "Hello NatureGirl15, I am recently diagnosed with endometrial carcinoma 1B Grade 3. I had a total..." + (show)

@cls316. Welcome to Mayo Clinic Connect. I know this is a difficult time for you but you are most welcome to this very supportive site.

I don't know much about the molecular classifications that @val64 brought to this discussion. I'm going to tag @val64 as this is an area she knows about and can help you with.

val64 | @val64 | Nov 13, 2022

In reply to @cls316 "Hello NatureGirl15, I am recently diagnosed with endometrial carcinoma 1B Grade 3. I had a total..." + (show)

I'll try attaching the guidelines to this post, but that may not be successful.

The NCCN is annoying in that they make you register to get access to their most recent treatment guidelines. I used an account from my former job, but I think you should be able to register too. Go to https://www.nccn.org/guidelines/category_1. Select "Uterine Neoplasms". I can't see what it does at this point because it is automatically logging me in, but I think it will give you the opportunity to register or log in. You probably need to say that you're a healthcare provider or medical professional.

I realized a number of things after I started this thread. One is that POLE mutation testing is most definitely NOT standard of care for endometrial cancer in the US, and almost no hospitals offer it to newly diagnosed patients. You can sort of figure out why from the NCCN guidelines: although they recommend POLE testing, the treatment algorithms don't include the results at all. This contrasts with the European guidelines (https://ijgc.bmj.com/content/31/1/12.long), which recommend considering no treatment for patients with POLE mutations. No US physician is going to recommend foregoing treatment because of this mutation without it being in a set of official guidelines. So if you want to use this in making a decision, the doctor is going to argue against you.

The immunohistochemistry for mismatch repair (MMR) genes and for p53 should be on your pathology report. If there is an MMR defect, then there's probably no point in looking at POLE. Being "positive" for p53 doesn't rule out a "good" POLE mutation, but probably makes it less likely.

I'm happy that I spent $450 out of pocket to get the POLE test done at Stanford, even though I didn't get the result I wanted. I'm not completely sure what I would have done if it had been positive, but I definitely would not be having chemo. Since then, I have also had a multi-gene sequencing panel done on my tumor, because I'm a molecular nerd, but if you want to do that, be very careful about what they are going to try to charge you, if/when insurance doesn't cover it. (The list price at my hospital is well over $10,000. But after investigating, I'm getting it for less than $1000.)

Shared files

uterine (uterine.pdf)

cls316 | @cls316 | Nov 14, 2022

Thanks so much. I am going to Cleveland Clinic in Florida for a 2nd opinion this morning. Will ask about clarification of my p53 mutation and explanations of my path report. I did ask my gyn oncologist about getting the POLE test and he discouraged me (as you predicted).

cls316 | @cls316 | Dec 7, 2022

In reply to @val64 "I'll try attaching the guidelines to this post, but that may not be successful. The NCCN..." + (show)

@val64

I'll try attaching the guidelines to this post, but that may not be successful.

Jump to this post

Hi,
I've just gotten a 2nd opinion surgical path report consult. I don't understand some of it and am hoping that you can shed some light. What is MMR proficient mean? What is BRAF positive mean? Thanks so much.

val64 | @val64 | Dec 7, 2022

In reply to @cls316 "Hi, I've just gotten a 2nd opinion surgical path report consult. I don't understand some of..." + (show)

MMR stands for mismatch repair, which is cellular system for repairing a type of DNA damage that occurs normally in cells as they divide. All cells in our bodies carry out MMR. "MMR proficient" means that the mismatch repair system in your tumor is normal. Since this is the normal state, there are no clinical implications for the tumor being MMR proficient. (There would be clinical implications if the tumor were "MMR deficient," ie having defective mismatch repair. About 25% of endometrial cancers are MMR deficient, and testing for MMR is standard of care for endometrial cancers. )

The BRAF test is strange, and it makes me wonder if there's been some sort of miscommunication. I'm almost reluctant to comment on it, and you should definitely ask the doctor about it.

BRAF is a gene that is frequently mutated in certain types of cancers. As of 2 years ago, when I quit my hospital job, it was routine to test for BRAF mutations in certain thyroid nodules, in colorectal and lung cancers, and in melanomas. I see no reason to test an endometrial cancer for it, unless they just routinely do the test on every sample they get, which I guess is possible. BRAF mutations are extremely rare in endometrial cancers; the NCCN guidelines don't recommend or even mention testing for it; and BRAF testing is definitely NOT standard of care.

What would be standard of care would be to test for a different gene called p53. Does the report mention that?

The phrase "BRAF positive" would normally mean that your tumor has a mutation in the BRAF gene. But I am reluctant to draw that conclusion in your case, since that seems extremely unlikely. More likely some kind of miscommunication. I certainly wouldn't spend any time worrying about it either way, but I would ask.

I hope that answers your questions. (I know this is obvious, but let me add the disclaimer that I am a random stranger on the internet, and everything said by such people, no matter how sincere, should be taken with a grain of salt.)

annewoodmayo | @annewoodmayo | Dec 14, 2022

In reply to @val64 "I did manage to get a POLE mutation test on my tumor by having it sent..." + (show)

@val64

I did manage to get a POLE mutation test on my tumor by having it sent to Stanford ($450 as of Sept. 2022; I didn't mess with trying to get insurance to pay for it). This is the only place in the country that I could find that is advertising a single gene test for POLE and is interested in taking outside specimens.

However, most academic medical centers sequence POLE as part of a "next-generation sequencing panel", where they sequence dozens to a few hundred different genes in a single test. I would have rather had a sequencing panel done, but it took a long, educational investigation to figure out how much this would cost if insurance wouldn't pay for it (which they almost certainly wouldn't at my stage. Insurance is more likely to pay for a sequencing panel for advanced or recurrent cancers such as @mimito6's. I know this kind of thing because I'm a molecular biologist who used to work in a lab that did these panel tests.).

The hospital where I'm being treated has a "price transparency" spreadsheet that lists the cash price for such a panel at well above $10,000. I contacted the lab (which you're not supposed to do as a patient, but I was super-frustrated), and eventually they got back to me and said that I could self-pay for the panel for less than $1000 if the correct procedure was followed. So much for price transparency.

Anyway, my POLE test was negative, which is not the good outcome, so now I have to decide what to do.

I'm interested in what people think. My tumor is a Stage 1B, FIGO grade 3 endometrioid endometrial cancer. My current Dr. has recommended 3-6 cycles of chemo plus vaginal brachytherapy. I'm scheduled to start chemo next week. My insurance won't cover a second opinion at any of the very highly rated non-local hospitals, so I got a second opinion at the second large local hospital system, and they recommended pelvic radiation therapy; no chemo. I have an appointment for a 3rd opinion at a cancer center belonging to a third local hospital system next week, less than 24 hours before I'm scheduled to start chemo. I'm planning to decide for certain what to do after that, but am currently thinking that I will go ahead and start chemo.

What do you think has fewer long-term side effects? Chemo or pelvic radiation? I'll put up with the short term side effects, but would rather not be dealing with peripheral neuropathy, lymphedema, urinary, bowel problems, etc. for the rest of my life.

Jump to this post

Golly, I'm so new at this stuff that I have nothing to advise. Just want to wish you good luck!

jjevitts | @jjevitts | Oct 1, 2023

Hi,
I was just wondering if anyone could explain the POLE testing and the effect in endometrial cancer? I was tested and found to be POLE negative, which is my understanding not the outcome you want. Does it effect the prognosis? Or recurrence?
I’d so appreciate any insight. I’ve read quite a bit, but it’s so technical. Thanks so much!

Helen, Volunteer Mentor | @naturegirl5 | Oct 1, 2023

In reply to @jjevitts "Hi, I was just wondering if anyone could explain the POLE testing and the effect in..." + (show)

@jjevitts Hello, @val64 started a discussion on POLE testing. Some of your questions might be answered by reading this Discussion and responses.

https://connect.mayoclinic.org/discussion/testing-endometrial-cancer-for-mutations-in-the-gene-pole/

I’ve tagged @val64 as she is very knowledgeable about this and I’m hoping she will jump in here and provide you additional information.

val64 | @val64 | Oct 1, 2023

In reply to @jjevitts "Hi, I was just wondering if anyone could explain the POLE testing and the effect in..." + (show)

POLE mutations are present in about 10 percent of endometrial cancers and and are associated with a good prognosis and a very low risk of recurrence. If the test had been positive, that would have been something to celebrate, but a negative result doesn't really change the outlook on your situation either positively or negatively. Let me know if that doesn't answer your question.

View More View Less

Please sign in or register to post a reply.