HER2 status not consistent

Posted in TCGA data on the CGC by Maor Maor Mon Oct 29 2018 11:48:36 GMT+0000 (UTC)·8·Viewed 46 times

I got the HER2, ER, PR status of BRCA patients from the BRCA TCGA publication supplementary: https://www.nature.com/articles/nature11412#supplementary-information filename: TCGA_Supplementary Tables 1-4.csv column: HER2_Final_Status But since it is from 2012, after some months, I downloaded the newer clinical data from cbioportal**: http://www.cbioportal.org/study?id=brca_tcga#clinical filename: data_bcr_clinical_data_patient.txt columns: IHC-Status, HER2 fish status However, I noticed that hundreds patients had different her2 status then they had in the old tcga publication: Barcode IHC-status(cbioportal) Her2 fish status (cbioportal) HER2_Final_Status(tcga publication) TCGA-A1-A0SH Equivocal Negative Negative TCGA-A2-A04U Negative Positive Negative TCGA-A2-A0T2 Negative Not Evaluated Negative TCGA-A8-A06R Positive Positive Equivocal At first, I thought there is a method to convert both ihc and fish statuses into one (final status). But I failed to find such method. In TCGA-A1-A0SH, it seems Fish is prefered. In TCGA-A2-A04U , it seems it is IHC. in TCGA-A8-A06R it is neither. **I verified that for those 4 patients, her2 status is consistent between cbioportal and current TCGA clinical files. (her2_fish_status, her2_status_by_ihc in clinical files) Thanks in advance, Maor
Maor Maor
Oct 30, 2018

Also, in current tcga data, there is mismatch between ihc score and ihc status for almost 10% of patients.
For example:

TCGA-AC-A8OS, has ihc score of 1, but ihc status Positive.

I am probably missing something. Any advice would be appreciated.

Aleksandar Jovic
Oct 30, 2018

Hello Maor, in the document on following link you can find out information that could be helpful. 
http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2013-0953-SA

Maor Maor
Oct 30, 2018

Hey, Thanks Aleksander for the quick reply :)

So as far as I could understand, in 2013 there have been a change of guidelines. Which explain the differences between the 2012 tcga publication and current data.

But I still do not understand in current data, how patient TCGA-AC-A8OS for example, has IHC score of 1, and IHC status Positive. IHC score 0+,1+ is Negative, 2+ is Equivocal, and 3+ is Positive (for IHC test).
Am I missing something?

Aleksandar Jovic
Oct 31, 2018

HER2 test result must be reported as positive for HER2 if:

IHC 3+ based on circumferential membrane staining that is complete, intense
ISH positive based on:
1. Single-probe average HER2 copy number > 6.0 signals/cell
2. Dual-probe HER2 /CEP17 ratio >= 2.0, with an average HER2 copy number >= 4.0 signals/cell
3. Dual-probe HER2 /CEP17 ratio >= 2.0, with an average HER2 copy number < 4.0 signals/cell
4. Dual-probe HER2 /CEP17 ratio < 2.0, with an average HER2 copy number >= 6.0 signals/cell

This is straight from the document previously linked, Table1 on Page6.

Though, on the http://www.cbioportal.org/study?id=brca_tcga#clinical portal, some of these values seem to be missing. Why this is so, I'm afraid we can't know. So, we would kindly recommend contacting cBioPortal staff for more details.

Maor Maor
Oct 31, 2018

I apologize if I miss something obvious :)
But Her2 IHC score of 1, and Her2 IHC status Positive, seem like a contradiction to me.
(only IHC now, no FISH)

A Her2 IHC test has one result (score), which determines the (Her2 IHC) status.

(Example: TCGA-AC-A8OS, Her2 IHC score 1, Her2 IHC status Positive )

No?

Aleksandar Jovic
Oct 31, 2018

I think Her2 IHC status is determined not just by the Her2 IHC score, but by both the Her2 IHC score and FISH status, as previously described.

It's in this document
http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2013-0953-SA
on page 2.

So in short, HER2 test result is positive if:

  1. IHC score is 3+, OR
  2. FISH status is positive (this is determined by the method described in Table1 on page 6 in the previously linked document).
Maor Maor
Oct 31, 2018

Thank you, I appreciate the help :)

But then there are patients such as TCGA-AO-A0JL who have :

  1. Her2 IHC score = 1
  2. Her2 IHC status = Negative
  3. Her2 Fish status = Positive

Positive OR Negative should have given Positive

Aleksandar Jovic
Oct 31, 2018

Her2 status will be negative if either IHC score is 1, or FISH status is negative.
In this case that he linked, FISH status is positive, BUT IHC score 1, so Her2 status will be negative.
It's in document
http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2013-0953-SA
on page2.

  
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