My mom's pathology report

adamfong

To anyone who can decipher this. I just need to know whether my mom falls under HER2+. I fear that she has been misdiagnosed.

Thank you in advance.

pupmom

Hard to read/decipher that report. Best option is to just call her doctor and ask. There's absolutely no reason why they wouldn't tell her whether, or not, she is HER2+. Best wishes!

Leslie2016

I don't think you have the info yet. The receptor status can take longer than the initial pathology you get. I don't know when her biopsy or surgery was, but it can take 10 days or more I think (if I'm remembering correctly) for the ER/PR/HER2 info to be ready. So you have to wait for the addendum report...or find it. That info is NOT on this report. It doesn't mean she's misdiagnosed, just you don't have all the pieces yet.

BarredOwl

Hi Adamfong:

As we are just patient layperson's with no medical training, no one here can tell you whether she was correctly diagnosed or not. Please seek expert advice.

One addendum states that the tumor was ER-negative and PR-negative. HER2 testing by immunohistochemistry (IHC) was "equivocal with score 2+."

In the case of an "equivocal" result by IHC, under ASCO/CAP guidelines for HER2 testing (2013), "reflex" testing by an alternative method is indicated. In her case, per the second page above, further ISH testing was done using HER2 Dual Probe In Situ Hybridization (ISH), on a Ventana Inform HER-2/Chr17 Dual ISH platform.

The pathologist's interpretation of this reflex HER2 testing, said to be based on on ASCO-CAP Guideline 2013, was:

In situ Hybridization (ISH): Positive

(HER-2/Chr more than or equal to 2.0 with average HER2 copy number more than or equal to 4.0 signals/cell)

This pathologist considered the results to be "Positive" by ISH, which would indicate HER2-positive status.

Assuming the test was performed properly using validated assay, the conclusion appears to be consistent on its face with the 2013 ASCO/CAP guidelines:

2013 ASCO/CAP Guideline: http://ascopubs.org/doi/pdf/10.1200/JCO.2013.50.9984

(Free pdf available under PDF tab; see also, Supplements)

See Figure 3, which summarizes evaluation of human epidermal growth factor receptor 2 (HER2) gene amplification by in situ hybridization (ISH) assay.

At the far left, you can see that your Mom's particular result: a finding of "HER2/CEP17 ratio ≥ 2.0" and "Average HER2 copy number ≥ 4.0 signals/cell" is one of the types of findings that would be considered "ISH positive" (assuming that there is "no apparent histopathologic discordance observed by the pathologist").

If you have doubts about her test results, such as the pathologist's conduct of the test; his evaluation of any readout (e.g., Average number of Her-2 Signals/nucleus; Average number of of Chr 17 Signals/nucleus; working controls); or proper application of ASCO/CAP guidelines to determine HER2 status, you could seek an expert pathology review. Pathology slides are sent overnight (with tracking) to a second independent institution for review by another pathologist. You could request that the pathologist at her current private hospital conduct such a review.

I saw in another post that you and your Mom are located in Malaysia, and after only 5 cycles of adjuvant chemotherapy, she was diagnosed with metastatic disease. I was very sorry to learn that. You are understandably wondering if a trastuzumab-based regimen could have either prevented or delayed it. Please discuss this question with her current medical oncologist. You may also wish to inquire how access to trastuzumab (Herceptin) is determined, and whether the government hospital followed any applicable guidelines or regulations regarding allocation of the drug.

BarredOwl

MTwoman

Looks to me like "HER2 positive" based on ISH (stated "HER2 more than or equal to 2 with average copy number at 4 signals/cell") from page 2 and Addendum diagnosis on page 3 stating HER2 equivocal with a score of 2+. I'd absolutely want to clarify those 2 pieces of conflicting info with my physician. (it IS very hard to read).

NotVeryBrave

I think that they only treat as HER2 positive if the results are 3+ for staining. Since it looks like the hormone receptor status is negative, endocrine therapy probably wouldn't be recommended. It may be worth having a different HER2 analysis done for confirmation.

MTwoman

but the results state HER2 positive with 4 signals/cell. I'd want this clarified.

BarredOwl

Hi Adamfong:

Because we are just patient layperson's with no medical training, no one here can tell you whether she was correctly diagnosed or not, including whether the ISH test was both properly conducted and interpreted. Please seek expert advice.

Here is some background information. My layperson reading is that one addendum states that the tumor was ER-negative and PR-negative. HER2 testing by immunohistochemistry (IHC) was "equivocal with score 2+."

In the case of an "equivocal" result by IHC, under ASCO/CAP guidelines for HER2 testing (2013), "reflex" testing by an alternative method is indicated. In her case, per the second page above, further ISH testing was done using HER2 Dual Probe In Situ Hybridization (ISH), on a Ventana Inform HER-2/Chr17 Dual ISH platform.

Based on his finding of a "HER-2/Chr [17 ratio] more than or equal to 2.0 with average HER2 copy number more than or equal to 4.0 signals/cell", the pathologist considered these results to be "Positive" by ISH.

In general, a tumor that is initially "equivocal" by IHC, and then deemed "positive" by validated ISH, is considered to be HER2-positive. The 2013 ASCO/CAP guidelines for HER2 testing can be found here:

2013 ASCO/CAP Guideline: http://ascopubs.org/doi/pdf/10.1200/JCO.2013.50.9984

(Free pdf available under PDF tab; see also, Supplements)

See Figure 3, which summarizes evaluation of human epidermal growth factor receptor 2 (HER2) gene amplification by in situ hybridization (ISH) assay.

At far left, you can see that a finding of "HER2/CEP17 ratio ≥ 2.0" and "Average HER2 copy number ≥ 4.0 signals/cell" is one of the types of findings that would be considered "ISH positive" (assuming that there is "no apparent histopathologic discordance observed by the pathologist").

A proper determination must be based on the use of a validated test that was properly conducted. While you can find more information about the test at www.ventana.com, sample quality must be adequate and the controls, counting methods, and ratio determinations must be correctly performed.

If you have any doubts about the conduct or interpretation of the HER2 testing or the proper application of ASCO/CAP guidelines to determine HER2 status, then you should seek a second opinion pathology review based on the pathology slides. Pathology slides can be sent overnight (with tracking) to a second independent institution for review by another pathologist. You could request that the pathologist at her current private hospital conduct such a review.

I saw in another post that you and your Mom are located in Malaysia, and after only 5 cycles of adjuvant chemotherapy, she was diagnosed with metastatic disease. I was very sorry to learn that. You were wondering if a trastuzumab-based regimen could have either prevented or delayed it. Please discuss this question with her current medical oncologist, who can provide his professional opinion and explain any gray areas or unknowns. You may also wish to inquire or research how access to trastuzumab (Herceptin) is determined, and whether the government hospital followed any applicable guidelines, regulations, or policies regarding allocation of the drug or informing requirements (if any).

BarredOwl

[Edit: Revised some wording in last paragaph]

adamfong

Thanks everyone. I appreciate these answers.