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- B1580what scores of the IHC Her 2stain you will give (cqz 14)
笃行者 said: 我们应用的诊断标准和你们一样，但我们在判断3+时比较保守一些，怕吃官司。比如对于病例1和病例2我们都会判为2+。叫病人花几千块钱做FISH，总比花十几万块钱做无效治疗强。还不会被告上法庭。（况且国内免疫组化的质量控制还存在一些问题）
This is very good. I used the same pholosophy for the evaluation of Her2 IHC. Until the stains are very strong like positive control (see my above control photos), otherwise we call 2+ and the FISH will be done.
In fact I called 2+ for both the case 1 and 2. This is why I can have the FISH result.
Learning to evaluate Her2 IHC stains is very important. Hope all pathologists are aware of this espcically for the people who do not read the stains often.
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Basically I complete this topic. Anti Her 2 drug, Trastuzumab is too expensive for individual usage. Her2 issue may be not very mportant for general pathologists in China now. I assume it will become important soon.
Trastuzumab (Herceptin) is a monoclonal antibody that interferes with the HER2/neu receptor.
Thank all people for reading or discussing this topic.
cz
http://arpa.allenpress.com/pdf/i1543-2165-131-1-18.pdf
Above is American Society of Clinical Oncology/College of American Pathologists Guideline recommendations for human epidermal growth factor receptor 2 (Her2) testing in breast cancer.
This is the best and standard paper in the US.
To Abin:
In fact most American general pathologists do not know the information in details also in this area. I know some because I am a breast pathologist.
Her2 gene is located in Chromosome 17.
CEP 17 is a centromeric probe for chromosome 17.
Now American Society of Clinical Oncology/College of American Pathologists Guideline:
Her2/CEP 17 ratio>2.2: positive for Her2 gene amplification.
Her2/CEP 17 ratio <1.8: negative for her2 gene amplification.
Her2/CEP 17 ration 1.8-2.2: Equivocal Her2 gene amplification.
If the ratio >=2.0, the patients are eligible for adjuvant trastuzumb treatment.
Prognostic Biomarkers - HER2/neu by FISH
Indications for use
The proto-oncogene HER-2/neu (c-erbB-2) resides on chromosome 17q and encodes a trans-membrane tyrosine kinase growth factor receptor. Amplification of the HER-2/neu gene, or overexpression of the HER-2/neu protein, is found in 20-30% of breast cancers. There is a greater than 90% correlation between gene amplification and protein overexpression. Some studies suggest that HER-2 gene amplification assessed by Fluorescent In Situ Hybridization (FISH) may improve the predictive ability of this marker for Trastuzumab (Herceptin®) therapies (1, 2), especially in the 10-20% of cases with equivocal (i.e. 2+) results for protein expression by IHC . The primary indication for assessing HER-2 by FISH today is in cases with equivocal IHC results (3, 4).
Scoring/interpretation
In our laboratory, we use PathVysion, a FDA-approved kit for HER-2 testing by FISH and follow the scoring and interpretation recommended by the manufacturer. In this procedure, the chromosome 17 centromere is marked with a green florescent signal and HER-2 gene with an orange florescent signal. Briefly, we assess 60 non-overlapping tumor cell nuclei and count the number of green and orange signals in each cell. Then, the overall gene-to-chromosome (17) ratio is calculated. A tumor is designated as “positive” for gene amplification if gene-to-chromosome (17) ratio is >2.0
Detailed procedure
We use FDA approved PathVysion kit to assess HER-2 by FISH. As per manufacturers’ recommendation, 20 tumor non-overlapping cell nuclei are enumerated to obtain the HER-2/chromosome 17 ratio.
Her2 FISH was performed on both cases.
Case 1: Fish ratio: 1.06
Case 2: Fish ratio: 2.08
Fish ratio=Her2/CRP17. CEP 17 is a centromeric probe for chromosome 17, where Her2 gene resides.
Some ones please explain above FISH results about Her 2 gene amplification, negative, equivocal, or positive for both cases.
Thanks, cz
Abin:
I read your last sentence: 流汗！我怎么看反了？ I think again for your reaction. I will be very happy if you wrote that Zhao or Dr. Zhao, you were wrong in the score or why the score was 3 in the first case. We, Chinese are very traditionl. We respect olders, seninors, professors, experts, teachers, or authority. But in filelds of sciences, in medicine, especially in the internet, we should observe the truth. I am sure that you knew I was not correct (you maight think Zhao gave a stupid answer), but you still said 我怎么看反了.
You should say that zhao, 你怎么看反了.
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本帖最后由 于 2009-03-12 01:20:00 编辑
First case, definitely we should NOT call pasitive (score 3). (sorry I did not type not in the begining until I saw abin's talk)
Second case, I agree with most of you. It should be score 3 based on the criteria. But it still has weaker stain compare with control. It is too important for pathologists to call positive or negative. For this purpose I called both cases eqivocal (score 2). Automatically the Her2 FISH will be performed on the cases with score 2 in our institute. I will let you know the fish results when I am back Pittsburgh.
| 以下是引用杨宝军在2009-3-2 21:39:00的发言：
2 请问：Dr. Zhao,评分是以强度为主还是以数量为主，还是两者结合，如果是，怎么结合？ 如果没有参照组织片依靠什么标准判断强度？ |
See this topic. http://www.ipathology.cn/forum/forum_display.asp?keyno=16236
The guidline paper.
http://jop.ascopubs.org/cgi/content/full/3/1/48
Brief description about the scores
Tissue fixed using formalin 8-96 hours.
0 = No staing is observed or membrane staining is observed in less than 10% of the tumor cells.
1+ = A faint/barely perceptoble membrane staining is detected in more than 10% of the tumor cells. The cells are only stained in part of their membrane
score 0, 1 called negative
2+ = A weak to moderate complete membrane staining is observed in more than 10% of the tumor cells.
2+ means equivocal
3+ = A strongly complete membrane staining is observed in more than 30% of the tumor cells.
3+ means positive.
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本帖最后由 于 2009-03-01 10:45:00 编辑
| 以下是引用Elizabeth在2009-3-1 8:26:00的发言：
Yes, the sitiuation is same in our hospital. |
How about other hospitals in China?
As pathologists are you sure that the patients should receive Herceptin treatment? We call positive the oncologists may provide this drug for these women.
Hope every one checks the websites and know the price of the medicine and side effect. Are you confident?
http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=50242013468&trx=1Z5006
http://www.chemocare.com/bio/herceptin.asp
http://www.breastcancer.org/treatment/targeted_therapies/herceptin/
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本帖最后由 于 2009-03-01 03:04:00 编辑
See your scores above.
Positive controls:
Fig 1-2 for case 1, 200x, 400x.
Fig 3-4 for case 2, 200x, 400x.
The control tissue and sample were in the same slide.
Now do you want to change your score?
If you score 3, the oncologists will treat patients based on her2 positive.
If you score 1, it means Her 2 is negative.
If you score 2, the Her2 Fish will be performed.
Above are what we are doing in our hospital. How about in China?
名称：图1
描述：图1
名称：图2
描述：图2
名称：图3
描述：图3
名称：图4
描述：图4
The interpretation of ER, PR and Her2 stain results is critical for oncologists to treat invasive breast cancers with neoadjunvant chemotherapy before or after the surgery. From here you can tell that we, pathologists play a very important role in patient care.
I showed two cases above. If there are your cases, what score (0, 1, 2, 3) will you give?
Negative: 0-1
Equivocal: 2
Positive: 3
