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

Posted by val64 @val64, Sep 3 10:03am

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 group.

@val54. I didn't know about POLE mutation testing so I looked it up.
https://www.mskcc.org/cancer-care/patient-education/about-mutations-pole-gene.
https://www.mayoclinic.org/medical-professionals/digestive-diseases/news/inherited-cancers-clinic-seeks-to-advance-understanding-diagnosis-and-management-of-hereditary-colorectal-cancers/mac-20430193
I do know that there was gene testing on my tumor specimen in 2019 but POLE mutation testing was not one of them. Insurance (BC/BS) covered all of my gene testing at that time.

I'm curious why you'd like to have POLE mutation testing? Is it for the prognostic value as you mentioned or do you have a history of colon or rectal cancer in your family? Is there a clinical reason that your oncologist can make the case for with your insurance company? So-called "screening" without specific clinical or diagnostic reasoning often results in no coverage from insurance. (For what it's worth, I don't like this. I had to fight with my insurance company when I had my first screening colonoscopy as recommended by the AMA at the time).

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@naturegirl5

@val54. I didn't know about POLE mutation testing so I looked it up.
https://www.mskcc.org/cancer-care/patient-education/about-mutations-pole-gene.
https://www.mayoclinic.org/medical-professionals/digestive-diseases/news/inherited-cancers-clinic-seeks-to-advance-understanding-diagnosis-and-management-of-hereditary-colorectal-cancers/mac-20430193
I do know that there was gene testing on my tumor specimen in 2019 but POLE mutation testing was not one of them. Insurance (BC/BS) covered all of my gene testing at that time.

I'm curious why you'd like to have POLE mutation testing? Is it for the prognostic value as you mentioned or do you have a history of colon or rectal cancer in your family? Is there a clinical reason that your oncologist can make the case for with your insurance company? So-called "screening" without specific clinical or diagnostic reasoning often results in no coverage from insurance. (For what it's worth, I don't like this. I had to fight with my insurance company when I had my first screening colonoscopy as recommended by the AMA at the time).

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Many thanks for responding so quickly and for the info. Was this at Mayo?

I'm interested in it for the prognostic value. (I do not have colorectal cancer in my family.) I will feel quite differently about further treatment depending on the result.

I also think it is a reasonable thing to want because the most recent version of the NCCN Guidelines for endometrial carcinoma recommends molecular classification based on 3 tests: POLE sequencing, immunohistochemistry (IHC) for mismatch repair (MMR) proteins, and IHC for p53 (ENDO-A p. 3 of 4). This is based on a number of publications over the last few years that categorize endometrial carcinomas into 4 groups: 1) POLE mutants (from sequencing), 2) mismatch repair defective (from MMR IHC), 3) copy number high (from p53 IHC), and 4) copy number low (everything else). POLE mutants have a very good prognosis, while copy number high have the worst prognosis, and includes some high grade endometriod carcinomas as well as serous carcinomas.

Many POLE mutant cancers are like mine, presenting with high grade and greater depth of myometrial invasion. But some copy number high cancers are also like mine. I will feel quite differently about how aggressively my cancer should be treated if it's POLE mutant vs. copy number high. (IHC for MMR and p53 have been done on my specimen.) Once I'm given a treatment plan from my current team (hopefully soon), I'll have to decide whether to go looking for a second opinion, and whether I'll have to make access to a POLE test a criteria for where.

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@val64 Hello, again. This is so way out of my league as I don't have a medical degree or a degree in a molecular biology field.

I was a patient at Mayo in Rochester. I had a total hysterectomy with bilateral salpingo-oophorectomy. My diagnosis was Endometrial Adenocarcinoma, Stage 1a. FIGO Grade 1. Myometrial invasion was 2mm, with depth of myometrium at 19mm and 10.5% myometrial invasion. Sentinel node biopsies were negative.

Were you surprised by your diagnosis or did you know this was likely the case? How are you feeling with all of these changes in your life and decisions you will be making?

Here is what I located in my test results:

MMR Protein and IHC were performed but no POLE testing.

Result Provided diagnosis: endometrial adenocarcinoma
IHC: Normal expression of MLH1, MSH2, MSH6, and PMS2p

No adjuvant treatment was recommended when I was first diagnosed.

I wonder if other Mayo Clinic Connect members have had POLE testing? I haven't seen specific discussions on this.

Will you let me know what your cancer care team recommends for treatment and if you seek out a second opinion where you will go? If you decide on a second opinion at Mayo here is the link:
http://mayocl.in/1mtmR63

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@naturegirl5

@val64 Hello, again. This is so way out of my league as I don't have a medical degree or a degree in a molecular biology field.

I was a patient at Mayo in Rochester. I had a total hysterectomy with bilateral salpingo-oophorectomy. My diagnosis was Endometrial Adenocarcinoma, Stage 1a. FIGO Grade 1. Myometrial invasion was 2mm, with depth of myometrium at 19mm and 10.5% myometrial invasion. Sentinel node biopsies were negative.

Were you surprised by your diagnosis or did you know this was likely the case? How are you feeling with all of these changes in your life and decisions you will be making?

Here is what I located in my test results:

MMR Protein and IHC were performed but no POLE testing.

Result Provided diagnosis: endometrial adenocarcinoma
IHC: Normal expression of MLH1, MSH2, MSH6, and PMS2p

No adjuvant treatment was recommended when I was first diagnosed.

I wonder if other Mayo Clinic Connect members have had POLE testing? I haven't seen specific discussions on this.

Will you let me know what your cancer care team recommends for treatment and if you seek out a second opinion where you will go? If you decide on a second opinion at Mayo here is the link:
http://mayocl.in/1mtmR63

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I'll definitely let you know the outcome of my quest for a POLE test.

I was not surprised by the diagnosis. My ultrasound report from early June said "suspicious for endometrial carcinoma" which I figured meant that I almost certainly did have cancer, since the radiologist would hedge if they weren't sure.

What did surprise me was how long it took to get from that to the hysterectomy (mid-August). I had a D&C in July where they removed a large polyp, which the pathologists diagnosed as a high-grade endometrial carcinoma, but deferred typing until the hysterectomy. I started lobbying for molecular testing then (where by "molecular testing" I mostly meant POLE testing, but I guess I wasn't specific enough), and the doctor said it couldn't be done until the resection, because of the Pathology department's algorithm. Then over a month later I discover that what I really wanted wasn't part of the Pathology department's algorithm either. My main emotion this whole time has been frustration.

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I have just had a recurrence of ovarian cancer and my Dr at Mass General tested the original tumor and said I did have the pole gene or marker . She did say it gave them more options, but right now I’m doing 6 more rounds of chemo. Insurance covered the test.

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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.

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Sorry that the POLE test was negative. Did you have LVSI on your path report? Is that the rationale for the chemo?

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@esikora

Sorry that the POLE test was negative. Did you have LVSI on your path report? Is that the rationale for the chemo?

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I did have LVSI. That line of the report said "Present: Low (less than 3 vessel involvement)." When I asked the Dr. at hospital 2 why he was recommending pelvic radiation, he cited the GOG 249 clinical trial, where they found this to be equivalent to (or maybe slightly better than) 3 cycles of chemo + VB for high risk early stage patients such as myself. When I asked the NP at hospital 1 why they recommended chemo + VB, she said it was because my tumor was p53 positive. (I'm not convinced "positive" is the right word for the result: they did IHC on two slides containing tumor, and one was "focally positive" while the other appeared to be negative.)

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@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

Chemo. I am suffering from radiation side effects since I had my radiation + vb. I have a lot of small intestine cramping and diarrhea due to the effects of radiation. I am now on TPN for my nutrition because I am unable to eat due to the damage to my intestines done by radiation. Chemo was a piece of cake compared to this.

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@mimito6

I have just had a recurrence of ovarian cancer and my Dr at Mass General tested the original tumor and said I did have the pole gene or marker . She did say it gave them more options, but right now I’m doing 6 more rounds of chemo. Insurance covered the test.

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Welcome, @mimito6. You may wish to join the members in this discussion:
– Ovarian Cancer: What treatments did you have? https://connect.mayoclinic.org/discussion/ovarian-cancer-2/

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