Ki 67 vs Mitotic Rate

ck55

Ki 67 vs Mitotic Rate

ck55

    I was wondering if anyone here knew what the correlation, if any, is between Ki 67 and mitotic rate. Apparently they didn't do the Ki 67 marker on my tumor, but my mitotic rate was a 1. Can I assume the Ki 67 would have been low as well? I keep forgetting to ask my onc this question.

    Cyndi 

LizM

There is suppose to be some correlation but not in my case.  KI67 was done on my biopsy and was 30% which is high.  When I got the path report from my final tumor specimen after surgery my tumor was grade 1 with a low mitotic rate.  This discrepancy has bothered me and my oncologist explanation is that breast cancer is heteregeneous.  Because my tumor was 2 cm and managed to travel to one sentinel node I guess I should consider it aggressive.  My oncologist also did not place much importance on the grade since I had node involvement.  I had very aggressive treatment so I try to find comfort in that. 

TenderIsOurMight

Hi Cyndi,



It's not a perfect fit, but its close in general with one caveat.



Mitotic rate is determined by looking at the fixed tumor on the slide under high microscopic lens power (high power field, or hpf) and counting the number of cells actively dividing. The more actively dividing cells as reflected by mitotis, the more quickly the tumor growth.



Ki67 protein also reflects cell proliferation, is present in the cell nucleus and is a marker to determine the growth fraction of cells. However, it has largely been supplanted by MIB-1, a commonly used monoclonal antibody that detects the Ki-67 antigen, and yields what is called the Ki-67 labeling index which goes from low to high. MIB-1 has the advantage of being able to be performed on formalin fixed tumor.



A Mitotic rate of 1 is as you said, low. It would seem logical to assume that had a Ki67 marker been done, it would be on the low side too. A caveat to this logic is that breast cancer tends to be heterogeneous, and potentially, a different area of the tumor studied by either MIB-1 or mitosis may yield a different result. That is why the pathologist (or machine if it is automated) selects the area of the tumor with the most DNA and abnormal cells.



Wonderful news that your mitotic rate is low. All the best to you.

Tender

LizM

Tender, with what you said, would it then be thought to be more reliable from the final tumor specimen from the surgery where the pathologist can select the area with the most DNA as opposed to the a biopsy which is a very tiny portion of the tumor?  My biopsy showed IDC, grade 2, high KI67.  My final pathology report after removal of the entire tumor showed IDC and ILC, grade 1 and low grade DCIS.  I wanted to be hopeful about having a grade 1 tumor but because the biopsy had a high KI67 I have pretty much decided that my tumor was somewhat aggressive.  I tried to google KI67 and grade a while ago and read some articles indicating that it is unusual to have a high KI67 and grade 1.  This discrepancy in my pathology reports has always confused me.  My biopsy also showed an IHC of 2+ on her2 but a retest of final pathology showed an IHC of 0.  Is it possible that they do not take as much time in the accuracy of biopsies as final pathology because the main objective in a biopsy is to find out if it is cancer and with final pathology more information is needed to make treatment decisions.

TenderIsOurMight

Liz,



I sent you a pm.



Tender

Anonymous

I have a combo stage one cancer that is idc (just under 1 cm) and is idc, with lcis, multifocal. Triple positive. My mitotic score is one and ki-67 is 15% (says borderline on the report). However I met with an oncologist yesterday who referred to the ki-67 as high. I have an appointment with a sedond oncologist ont he 23rd and plan to ask more about that.

bluepearl

What I understand from oncology journals is mitotic activity is the most important prognostic factor of the three that give you your grade; a mitotic activity of 1 is very good. It also remains a excellent prognostic factor independent of tumor size and across all tumors from grade 1 to 111. This is why women with very small tumors with a high mitotic rate can still have positive nodes etc...but remember your grade is determined by three things; mitotic activity, tubular formations and nuclear...with mitotic being the most important. So you could have a 3, 1, 1 score and still be considered grade 1,,but at a higher risk. Ki67 is one of the markers used in ocotypedx assessment and has a fairly linear correlation with mitotic activity but NOT always. MY ki67 was less than 10% and was considered low, while anything above 13.25% is considered getting into the high range, with above 20% being high. There has been some chair-flinging among pathologists over this % thing....but we are not per cents....each of our cancers (and our bodies) is different. And the higher mitotic rates means cancer responds better to chemotherapy...as does higher Ki67. The slow growers can sometimes show up a few years down the pike too...good and bad to every breast cancer cloud, it seems.

Anonymous

This is interesting.  I've been trying to find more info on this.  So my tumor was initially a grade 3 (8/9)from my core biopsy.  However, when we got the surgical biopsy back...it said grade 2 (7/9).  My onc said it's very common to regrade...depends on who's reading the slides.

So I look at the reports and some moved a point up or down ~ but what I found very odd was that the mitotic rate changed from a 3 to 1!!   So is the pathology from the biopsy or surgery more reliable?  My Ki67% was also "high" from the biopsy - it just said >20%, didn't give an exact number.  But they didn't comment on the Ki67% on my surgery pathology.

I'm not even sure if I want to pursue finding out more about my pathology ~It's too late and it really wouldn't make a difference since I have already chosen my treatment based on my oncotype score.  But it still makes me curious.

Anonymous

My pathology was all from my biopsy as they took it all out, with clean margins that were still clean at bmx a month later. I went through the path report with my bs and my onc. At the end of the day, I think they are still working on the accuracy of recurrence using those factors. Like blue pearl noted, my onc said they were factors as part of the whole picture but not reliable as a single factor.



I read the same thing concerning mitotic rate being a good predictor, but also not sure it is fully proven

Beeb75

This idea may be a little out there, but for those of us who are premenopausal with hormone-sensitive cancers, I've wondered how our monthly cycles of estrogen and progesterone play into our cancer growth rate. 

For example, if you had a biopsy at a time of the month when estrogen or progesterone was surging, wouldn't you then have more cells dividing (fueled by your hormones)? And if you then had surgery at a different time of the month when your hormones would lower, perhaps you would then have a lower mitotic rate, or Ki-67?

Just an idea -- because I have always been confused by the fact that I had a fairly high Ki-67 (20 percent) and yet my tumor was called "slow-growing" by some docs because it was so highly ER and PR positive (90+ percent for both).   

MarieKelly

Unfortunately, just like most everything else that has a human factor involved in interpretation, there's interobserver variability in determining what the mitotic rate of a given tumor is. See the following as an example of the problem -

 http://iospress.metapress.com/content/3502200775577718/

You can never just depend on a single prognostic factor standing alone - everything must be taken into consideration and when there's a single result that doesn't quite fit in with everything else (i.e. a high mitotic index with an otherwise obviously grade 1 tumor, you need to question the validity of that oddball result.

AMP47

Marie makes some very important and solid statements.  My oncology nurse agrees with her statements referring to a possible wrong interpretation.  For example my grade was originally 2 but after redoing the process, I was a grade 1 with a mitotic rate of 1, also.   To be human is to error.  Its is our responsibility to make sure our information is correct.

For two years I have read many articles, university studies, papers about the concordance between Ki67 and grade.  Also, I have accessed several doctors and "popped" the question to them.  Since the Ki67 was not part of my pathology report, I began to worry when reading alot of the post on this site with Ki67 information pathology report. 

I have yet to read an article that does not discuss the concordance with ki67 and grade being: low Ki67 = low tumour grade.  The reason my report does not include Ki67 is because of newer techniques for determining proliferation rate is now being used.  

My oncologist said the mitotic rate is the most important number for me which was 1.  Also, they do not use Ki67 as a measure of survival anymore, or a prognostic factor for overall survival, at least in my area.

The Internet is full of medical journals, articles and studies dealing with the question.  Hope this helps.  Good luck in your research.   

kathleen1966

This is interesting!  Not sure how I found it, it is an old post.  I had a low mitonic rate of 1, which made my cancer a grade 2. I never had the Ki67 test.  Although my entire cancer area was large and I had multiple tumors, the largest was only 1.6cm and so my staging was based on the size of this tumor (in addition to the nodes). My cancer was also Her2, and so the low Mitonic score doesn't make sense.  I also had four positive lymph nodes and LVI invasion. My low mitonic score was the same in three different biopsies. It is the only thing about my cancer which was positive.

Anonymous

Kathleen, mine was 1 also, and I am her2 positive.

papaska4

I had a mastectomy 2 weeks after a breast biopsy and had a high Ki 67 on biopsy, but a low mitotic rate on my surgical pathology. I had been taking estradiol and prometrium for 9 months prior to the biopsy and stopped them the day of the biopsy. I've long thought that the hormones had something to do with the high Ki67, but the oncologist says probably not. However, I've found multiple journal articles which correlate high mitotic rate and high Ki67 and just found one showing that Ki67 is elevated during the luteal phase of the menstrual cycle (when estrogen and progesterone levels are high). If anyone is into journal articles, here it is:

Menstrual Cycle could affect Ki67 expression in estrogen recetor positive breast cancer patients

Journal of Clinical Pathology. 2015 Oct; 68(10):825-9. doi:10.1136

Since I want to believe positive things, I believe that my Ki67 was falsely elevated due to the hormones. I'm sticking with the low mitotic rate!