Just an update after visiting the surgeon yesterday. I received my preliminary biopsy results and I am MLH1/ PMS2 deficient.
MLH1 methylation testing is pending.
POLE testing is pending.
I couldn’t stop myself from googling, and it doesn’t look much positive. Very inconclusive on many levels. Very complicated molecular biology level explanation, that made my head spin), not very promising at the end.
Have anyone else been diagnosed with the same type?
Any information would be very helpful
Thank you!!
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Cat1966
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Hi Cat1966. I'm sorry to hear you had a missed diagnosis. I understand why you are worried. I was dismissed for four years as perimenopausal before anyone even did an ultrasound. I know it's hard not to stress out when you start reading. Just take it one step at a time and ask lots of questions of your physician.
I had similar deficiencies. I'm not a doctor and I don't know all of your info, but that doesn't sound like the worst news. As I understand it, that falls under mismatch repair. The methylation that is pending is to determine if that mutation is sporadic (random) mutation or a genetic inherited mutation for Lynch Syndrome which could mean someone may have a predisposition to certain cancers like endometrial and colon. Mine turned out to be sporadic. If it's genetic, they may do additional testing and observe for other future risks. But as far as that molecular type, It is considered intermediate risk. Pole is the lowest risk. P53 mutated carries higher risk (p53 wild type means not mutated if you see that anywhere). The mismatch repair type is I believe a candidate for the newer immunotherapies which have helped many women. But this is all just one piece of the puzzle. I was fortunate to end up early stage and was treated with surgery. But at one point they were worried because I had a concerning scan. So I spent so much time worrying and anxious. Turned out I had undiagnosed endometriosis. That made my scan look a lot worse. But the cancer itself was contained. I was stage 1a grade 2.
Your molecular type will be considered with your stage and grade, myometrial involvement, whether there is lymphovascular space invasion, or lymph involvement, other factors and your overall health to determine treatment. I would write down any questions as they come up so when you are with the doctor you remember what you want to ask. I know you have other health concerns. Just try your best to take things one step at a time as you move through this and ask all the questions you need so you feel confident in your care. Get a second opinion too if needed. Even just to confirm the findings so you don't worry about things being missed like with the prior doctor.
I wish you the best possible care and outcome fron your treatment. I know it's scary now. But you will have more answers and a treatment plan soon. The waiting is the hard part.
Thank you so much for your reply and detailed explanation.
It is awful that you were dismissed for so long and only got diagnosed after four years. It must have been heartbreaking!
Good news that even with the delayed diagnosis you were at the early stage.
What made me upset the most is that I was under yearly follow up and had my ultrasound yearly due to a very severe endometriosis (my ca 125 was at 900 at one point). After taking elagolix for 2 years my ca 125 became normal (17), as it is low now as well.
My gyno saw the polyp at 6mm, and missed it growing to 12 last year, this year it was removed at 22 mm, bleeding and cancer.
At one point, when it was found at 6mm, he mentioned the biopsy, but after, kind of dismissed it, as it was not big enough to worry.
My P53 are normal wild type, and for now my biopsy states Endometrioid carcinoma grade 2. ER and PR 80% and 50% of tumor cells nuclei respectively.
Beta catenin membranous staining.
I was not offered CT scan prior to surgery.
I don’t know why.
You have mentioned you had sporadic mutation. Was it for MLH1 and PMS2 or other proteins were involved? Did you get additional treatments because of that?
Have the doctor mentioned more frequent recurrences, as what I read about MLH1 sporadic deficiencies is that it is prompt to more frequent recurrences?
Thank you very much for reading and giving me some piece of mind by sharing your journey.
I can relate to some of this frustration. I have found that my doctors also miss lab readings and results. I now understand it is my job to check every result and question and press them for answers and explanations. I had some anomalies a few months after surgery. I was told it was "statistically insignificant" by oncology and my primary "wasn't worried" despite the fact that I told both of them I was deeply exhausted and struggling. Dr. Google couldn't give me any clear info. A few months later I developed IBS which lead me to more doctors, a new CT that still showed NED for cancer, but then showed changes to my lungs that again I was told she "wasn't worried" about yet no one could tell me why I had these changes. Eventually, I went to a rheumatologist to rule out other things. She did broader bloodwork. I was now being flagged as officially low on iron. This was Nov 2024. So when I went back through my old labs, I could see that going back to March 2024, I was very borderline on iron and the other anomalies that were statistically insignificant back then? Also related to potential anemia. But my primary just kept testing my TSH. So now I am doing some short term iron supplementation and the doc will recheck. No immediate concerns for autoimmune digestive stuff which is good. I also used a functional medicine herbal protocol to help with my IBS which may have been triggered by bad food at a time when maybe my gut bacteria was altered shortly after surgery from all the medications? Also, the lung changes are things that can happen with anesthesia from surgery. So did no one want to mention that can happen with surgery? This is just one of a few examples where if I didn't ask, no one would have called or messaged or followed up and explained. They do the labs and then no one goes over anything with you. A past primary used to do that. She would say, there were some anomalies but I looked at it and it's fine. That's it. Via message with the results. Never explaining what she meant by that. No follow up test. This was during the 4 years I was spotting too. There were several things like that with her. Which is why I ultimately changed doctors but it isn't necessarily better with a new doctor. I believe they get overextended. So now I make sure to write out questions and message them and request a follow up call or even make a follow up appt depending on whether it is a simple question or requires more time. All this to say, we have to be our own best advocate. It's frustrating to feel like important things can slip through the cracks.
In regard to your specific questions, I had to look up my pathology. Yes, same MLH1 and PMS2 as you. My estrogen and progesterone percentages were much lower. Not entirely sure how that plays in. Though I believe estrogen responsive is considered slower growing and maybe less risk where some of the more aggressive types aren't estrogen related at all but those aren't adenocarcinoma. Not sure though what lower E and P numbers like mine mean. Maybe a new question for my oncologist.
My current oncologist wasn't my surgeon. My surgeon moved out of state and I had to change doctors. I was stage 1a grade 2 no added treatment despite the intermediate risk mutations. Once they knew I didn't have lynch syndrome, nothing else was mentioned about that. I believe the trend these days is to deescalate a bit and not overtreat too much. But this depends on all of an individuals health factors and the doctor's perspective. While there are guidelines, each case can be different with individual factors outside of stage and grade. My actual tumor was confined to the uterus, no lymph involvement (7 nodes removed), no myometrial invasion, no lvsi. So that all seemed clear early stage. Oddly though, my pelvic wash came back positive. This gave me such anxiety. But apparently they do not add any treatment for this for early stage any more. My original oncologist just said no added treatment and didn't really explain much even when I asked questions. My new oncologist said that she doesn't even do pelvic wash samples anymore as that is not deemed a clear indicator of prognosis (related to studies with inconsistent results of correlation). The way I read it when I researched, somewhat like you, was those mutations were an intermediate risk, the positive wash could also indicate risk, and I feel like there was something else in my report too. Can't recall just now. But the new oncologist acts very certain that I am cured. It's hard when I've been in support groups and heard stories of women in similar situations who had recurrence not too far out and even some who had recurrence way further out beyond the 5 year follow up plan. I go for physical checks every 3 months. First I was told 3 to 4 months. Then my original oncologist said I could go every 6 months after my first exam. Which I questioned and then she said, I'm just saying you don't have to see me as often. Without any clear reason for the change. Though I know other women do go every 6 months. But I stuck with 3 months. However, my next exam is after a 6 month gap as my appointment was rescheduled twice by oncology. This bothers me.
Oncology doesn't do bloodwork, they don't do scans unless there is some change and symptoms. When I developed bowel issues, they did a scan. But neither oncologist believed in any added treatment because of my mutations. Those molecular types seem to be used more in advanced cases to advise which chemo or immunotherapy could be helpful. But not really as relevant in early stage where they believe surgery is more curative. I still worry.
What's hard is that all of these recommendations have changed over the years. So sometimes we are reading older recommendations online. It's important to look at current research. I also got a second opinion. They agreed no added treatment.
I also wasn't in menopause but this put me in surgical menopause. Which has been rough. I was originally told no hormones. But they now believe, based on reevaluating old studies, that hormone therapy MAY be ok in early stage. The doctor said "we believe" and "may" be safe. So that makes me concerned. There seems to be more agreement that vaginal estrogen is safe with hormone cancer because it just locally treats vaginal tissue and doesn't go systemic. It's very challenging to know what is the best decision when the information changes over time. There is research backing all of this up. But I still struggle with what is best for me. I am just trying to move on and pay attention to my general health and take care of myself. It's a lot and I know you have even more on your plate.
Be sure to write down your most important questions and ask the doctors. They can best explain all of your specific individual factors. It's good to be informed but also make sure you are reading newer research and not old info.
I can only imagine how frustrating it must have been to go through all these hardships, spotting and pain for four years! You are so right, we have to advocate for ourselves. I did learn this a hard way with my autoimmune liver disease diagnosis.
I already started looking for gyno oncologists for a second opinion after final biopsy report.
I have received my pre op appointment, meaning I would probably be getting a surgery within next 10 Days of so.
During my first appointment with the surgeon, she mentioned, that I would probably be stage 1 based on ultrasound and tests, not sure if it is going to be A or B, as I ve always had adenometriosis along with endometriosis. But you never know.
And I was not offered CT scan pre surgery.
Was MLH1 andPMS2 deficiency in your case due to methylation?
What I read regarding the protocol for testing for LS, if methylation is confirmed, there is no other testing.
Have you read about any other causes for MLH1 and PMS2 deficiency? Would be interesting to know.
I am in Canada, and I am not sure if anything else is offered at early stage with MMRd besides the surgery.
But I did read that this type of tumour is prompt to more recurrences.
3 months follow up seems like the best approach.
I am in menopause, that was induced with elagolix. I was told not to use hormonal based moisturizers, as I have atypical cells in my breast. I am trying to alternate different hormone free moisturizers. Some work better than the others. If you would like, I can share with you the names of the brands.
So my mutations were sporadic. Not related to Lynch. As I understand it, that just means it is random. No specific cause identified. There's a lot they don't really know for certain. However, another interesting bit of info ... I had done an at home microbiome test when I was having gut issues. It shows overgrown bad bacteria and deficient good bacteria and recommends foods to balance your gut. There is also a list of almost 300 types of bacteria identified. But they mostly focus on your top 10 for food recommendations. Anyway ... sometimes they give you info on what the bacteria do and even links to scientific research. One bad bacteria on my top 10 that was overgrown didn't have much info listed within that program but I googled it. There is a doctor at Mayo Clinic that is doing research on the link of this bacteria to endometrial cancer as women with our cancer often have high levels. It seems to be involved with processing estrogen in the gut somehow. They are researching correlation v causation. No clear answers yet just the correlation. This showed up months after my surgery so my question was does it still create risk for recurrence. I emailed the researcher. She did not know. They haven't looked at that to see if it correlates with recurrence.
There are so many things that influence our well being. So I am trying to discover the best diet for my health and body and keep my gut healthy and make sure I have healthy bloodwork, including blood sugar related stuff. Just keep inflammation down. No one really knows all the why's. Hard to determine if diet, environment, viruses, gut bacteria, stress, or bad luck with genetics and so on is the cause of cancer. Often it is the interplay of many factors.
Here in the US, it is more common to do the genetic profile after surgery. Interesting that you have that info prior. The mutation isn't the main factor in determining added treatment. That's usually more influenced by stage, grade, depth of tumor, etc. 1a often doesn't have added treatment. 1b might. But I have seen different doctors recommend different things anyway. If you look at the most recent FIGO staging, it explains the guideline recommendations. The molecular types are used more often to determine immunotherapy v chemo in advanced stages or higher risk types when the other factors indicate those treatments but even this is evolving with additional studies.
And yes, while they think it looks contained, they don't fully know until pathology post surgery. Sometimes tumor cells are too small to see with scans. Or like in my case, something looks suspicious but it turned out I also had endometriosis that had advanced and wasn't previously diagnosed and that was what looked suspicious before they did surgery and discovered it wasnt cancer on my ovaries. Both stage and grade can be changed with post surgery pathology because they have more tissue to examine. I know women who have had things go up or go down. My gyn lab said I was grade 1. My oncology lab looked at that same sample and said they mostly agree but I may be grade 2. Post surgery they graded me at 2. Others have had the grade go down. They also meet in tumor boards so with more than one pathologist looking at it they can come to different conclusions.
I have used moisturizers. Gynatrof, revaree and others. Some can be expensive. My oncologist also prescribed estradiol cream. I read the ingredients and it had parabens in it. So I didn't do that. The estrogen tablets seem to have less of those ingredients. I've also been told vitamin e and coconut oil are good moisturizers. Curious what you have found helpful. I wish things like revaree were covered under insurance here. The estrogen tablets (with insurance) and vit e suppositories seem the most reasonably priced for me. I have also read hylauronic acid is contraindicated in cancer but that may be more when taken internally. I feel like every time I research something there is some conflicting info on it. I often reference Memorial Sloan Kettering Cancer Center Herbal Database to look up supplements and treatments people suggest.
I also asked my oncologist since they thought hormone therapy was safe in early stage then could certain herbs also be safe that sometimes hormone cancer patients are told to stay away from. She just said, good question ...
So I am going to the basics. Mediterranean style diet, lots of veggies, some fruit. No added sugars no processed food. Work on reducing stress and improving sleep. Exercise with more focus on strength training to prevent osteoporosis. Then maybe a multivitamin and some omegas and vit d as I have often been low on that. I fast 12 to 14 hours over night. And who knows ... maybe I will be fortunate enough to keep living healthy.
I wish you all the best with your surgery. Hoping for the best possible outcome for you and limited additional treatment. Give yourself time to heal and recover fully. But it sounds like you've been through other things and should know some of this. It was all new to me. Keep us posted. Wishing you good healing.
You can also look up MD Anderson endometrial cancer treatment algorithm and that outlines their recommended protocols. They are a top cancer center here.
All the research you did is fascinating! And you are so right, our overall health begins in our gut! I started looking for answers 3 years ago, after PBC diagnosis. I ve been trying to be on anti inflammatory diet as much as I could, almost no dairy, almost no gluten ( I keep adding almost, as sometimes I have), no red meat, just fish and chicken not fried, boiled or baked, no sugar, no fizzy drinks, A lot of veggies. I take 2000 D and B12, C 1000. Also I take dandelion root from Sunrider for my liver. My hepatologist also recommended Alpha 20C from Sunrider for immune system. I did blood test for microbiome of the gut, I had few bacterias growth, like é coli, I took antibiotics for that one. And from time to time my gastro gives me probiotics to drink for a moth or so. I should do this test again. It is very interesting that you read about the connection between gut bacteria and endometriosis.
It was mentioned to me that the estrogen is being filtered by liver, so liver damage could provoke an excess of estrogen to the blood. But I did not find anyone with PBC and endometrial cancer.
As a moisturizer I use gynotrof as well. I was told by gyno to use natural oils like olive or avocado.
I only use natural/bio ph balance intimate wash. There are few on the market, I like puressentiel. There is UK based company YES, it manufactures bio lubricants plant/oil based, I buy on Amazon.
For FIGO staging I checked the link (thank you very much) and there are more stages like 1a, 1b, 1c, etc. Is this something new?
There is a lot of info out there, sometimes overwhelming!
Thanks for the moisturizer info. I've heard of YES products too. It's great that you have doctors who help guide you on some of these things. When I ask doctors, I find most don't have knowledge or answers or suggestions. Most of my questions get dismissed.
Yes, FIGO staging was updated in 2023 and it did change a bit. That's the thing with us researching online. You always have to look at when the article was published and see if there is any newer contradicting info. New studies appear, recommendations can change. They have updated the guidelines in other years too. I have found this difficult too because you can read conflicting info. It's a lot. So always discuss with your doctors.
Did your doc give you the microbiome test? Interesting they prescribed antibiotics. I used an OTC test. It was initially just for fun, curiosity when I was working on improving my diet but came back with all kinds of Interesting info. If your test was one you purchased individually, what brand did you use? The connection with the gut bacteria from the Mayo researcher was specifically for endometrial cancer not endometriosis. Here's a link to an article about it. cancerblog.mayoclinic.org/2...
I read an article via link you sent, it is very interesting. I will verify if I got tested for this particular bacteria. And I ll message you.
I only remember all was in norm accept E. coli.
The test I took was not a home test . It was a stool test I believe and maybe blood as well. There was a panel of about 30 different bacteria checked. I had it done in Europe, as I was seeing hepatologist there as well for my PBC. I was not able to get it done in Quebec, even privately. I ll research again and see if I could find a lab that could perform this test, possibly in another province.
Interesting. Where'd you find that info? Is there a link to an article? Or a title I can Google? The researcher at Mayo didn't say anything about that.
And yes, I tested positive for that bacteria in my microbiome. They don't test for specific things. They identify whatever is detectable and then lists your top 10 good and bad bacteria and suggest foods that are good for helping balance things out. Porphyromonas was one of my top overgrown bad bacteria. My uqterus wasn't tested for these things but if it is in the gut it can be other places. It does help process estrogen so it can be connected to the cancer that way.
So I just reread the article I linked for you. I see how it talks about the uterine microbiome. It also mentions s how it can be in other areas of the body. Bone, oral etc. The other interesting thing on the article is the mention of how it is connected to high succinate levels. I also had a different functional medicine test that showed I had high levels of that. So tests from two different companies show these two things were present for me. While not sampled from the uterus, it was interesting and scary to learn that I had these things in my gut. New inspiration to improve my gut microbes.
Most of our health problems are connected to the immune system that begins in our gut.
It is interesting what you said about succinate levels. I ve never done this one.
Going for the surgery tomorrow.
And the next thing on my list is to do a thorough microbiome test.
I read about the tests with broccoli sprouts worked on demythilisation of the mutated cells. Spoke with the nutritionist, and for now he approved adding it to my diet.
It went well with an only hiccup, the surgery was robotic, but the surgeon had to make a small additional incision on my lower abdomen to take out the uterus, that I knew was not small, but not grossly large, at 7cm. They advised me before the surgery on this plan.
And they still sent me home the same day.
This incision is what bothers me the most.
I started walking around the house, and took a very short walk today.
Glad to hear it went well even though there was the extra incision. Impressed that despite that you are walking around. I was up and walking right away too. It helps. Plus I was active prior so my body wanted to move. First day I just paced around my apartment. Next day I went outside and walked about 15 mins and then went back for a nap. By end of week I was doing long leisurely walks. Just upped it every day. Over the 6 weeks I was doing several miles a day. It was also a good distraction while waiting on pathology. That's the harder part. Wishing you all the best.
Hi Cat1966, I just wanted to say hi when I saw your post because I too have PBC and endometrial cancer (plus endometriosis and in Canada). It’s interesting to read your comment about how PBC may affect the metabolism of estrogen. I hadn’t thought of it before, but it makes sense! If the liver can make cholesterol artificially high, then why not estrogen too?
In my case I have had a bout with endometriosis for about 20 years. Was diagnosed with PBC only 3 years ago, but there was something going on with my liver undiagnosed as I was having my blood tests on the yearly basis for 30 years. And all my liver enzymes were close to minimal. Even at diagnosis they were not too high.
Yes it’s hard to know what came first. My enzymes went up out of the blue too, about two years ago. But from what I’ve read though, PBC is most likely to show up in mid life or later. What does surprise me is finding out I had endometriosis when I had a hysterectomy for cancer. All these years and I had no idea! Will be interesting to see a link between the three.
This is very true about PBC. It does « show up » in the midlife, mostly women.
Endometriosis is some type of pre disposition for cancer. It doesn’t mean that everyone who has endometriosis will develop cancer, but many women would have a confirmed diagnosis for endometriosis after cancer diagnosis.
In my case being diagnosed with endometriosis I was told that I had to watch for cancer at one point in life.
Great info from Snazzyto! The "deficient" in your report is actually good because it gives you more treatment options and better survival odds. Good luck and hugs!
Yes. There is a large group of women who are in the not specified category and it may be harder for the doctor to know the best treatment. Research in these areas is ongoing. But there are promising treatments that can help manage advanced disease more like a chronic condition. Never give up hope.
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Uterine Polyp Biopsies
Is anybody taking Everolimus and Anastrozole and Metformin for er+/pr+ endometrial cancer?
endometrial adenocarcinoma, grade 3
Flushed after chemo treatment 
Why no maintenance medication?
