{"id":246179,"date":"2012-09-16T15:41:35","date_gmt":"2012-09-16T15:41:35","guid":{"rendered":"http:\/\/www.eugenesis.com\/can-2007-ascocap-scoring-guidelines-for-her2-protein-expression-and-gene-amplification-be-applied-to-gastroesophageal-adenocarcinoma\/"},"modified":"2012-09-16T15:41:35","modified_gmt":"2012-09-16T15:41:35","slug":"can-2007-ascocap-scoring-guidelines-for-her2-protein-expression-and-gene-amplification-be-applied-to-gastroesophageal-adenocarcinoma","status":"publish","type":"post","link":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/pathology\/can-2007-ascocap-scoring-guidelines-for-her2-protein-expression-and-gene-amplification-be-applied-to-gastroesophageal-adenocarcinoma.php","title":{"rendered":"Can 2007 ASCO\/CAP Scoring Guidelines for HER2 Protein Expression and Gene Amplification Be Applied to Gastroesophageal Adenocarcinoma?"},"content":{"rendered":"

Review of: Tafe, LJ, Janjiigian
YY, Zaidinski M, et al.  Human Epidermal
Growth Factor Receptor 2 Testing in Gastroesophageal Cancer Correlation Between
Immunohistochemistry and Fluorescence In Situ Hybridization<\/a>.  Arch Pathol Lab Med<\/a>; 2011;135:1460-1465.<\/span><\/p>


\"Nrgastroher2\"<\/a>Experienced pathologists are
familiar with the bumpy and often controversial evolution of HER2\/neu testing
in breast cancer patients.  <\/span><\/p>

First, there was a breast
cancer drug trial<\/a> employing a poorly designed trial assay followed by release
of the high demand drug Herceptin<\/a> into a medical system without a remotely
adequate companion assay.  This was
followed by a confusing application of multiple anti-HER2 antibodies in no
standardized immunohistochemical assays interpreted by a range of pathologists
using different criteria all in parallel with a separate evolution of different
FISH assays.  <\/span><\/p>

Before arriving at a reasonable
degree of standardization as outlined in the 2007 ASCO CAP guidelines, there
was a relatively prolonged period of sometimes heated consternation over which
assay was best, under what conditions, and using interpretive criteria.  And, during that period, we wrestled with a
lot of published laboratory correlation studies—the vast majority lacking any
clinical outcome data.  It’s not pleasant
to recall all of this controversy associated with HER2 testing in breast cancer
but hopefully it is a reminder of mistakes not to be repeated.  <\/span><\/p>

We should remember these
lessons as we step into a new era of anti-HER2 therapies for gastroesophageal
and almost certainly other cancers from other primary sites.  The combination of Herceptin and chemotherapy
was very recently proven effective against HER2 positive<\/a> advanced gastric and
gastroesophageal junction carcinomas in the TOGA clinical trial.  <\/span><\/p>


\"Gastricher2\"<\/a>Of great importance, the
standardized HER2 scoring systems used for breast cancer were not used in this
trial.  Instead, a body of preceding work
suggested that an alternative scoring system was needed for gastroesophageal cancers.  Basically, the traditional breast scoring
requirement for complete circumferential staining was modified to score
incomplete basal lateral membrane staining of gastric cancers as positive.  <\/span><\/p>

In the trial,
immunohistochemistry was slightly more powerful than FISH in predicting drug
response with therapeutic responses in IHC 3+ tumors as well as IHC 2+ FISH
amplified tumors but not in FISH amplified tumors with lower
immunohistochemical scores 1 and 2.  <\/span><\/p>

As a result, in Europe patients
with advanced gastroesophageal adenocarcinoma who are HER2 3 positive by
immunohistochemistry or IHC 2 positive with FISH amplification are eligible for
Herceptin therapy.  Slightly differently
in the United States, metastatic tumors that are IHC 3+ or HER2 amplified by FISH
are eligible.  <\/span><\/p>

Some investigators have not
bought into the modified HER2 scoring system and hope to justify a more uniform
application of the existing breast cancer scoring system across different tumor
types.  Reporting in the November 2011
issue of Archives of Pathology and Laboratory Medicine [provide reference],
senior author Violetta Barbashina and co-authors measure concordance between
immunohistochemistry and FISH for evaluating HER2 status in gastroesophageal
carcinomas.  <\/span><\/p>

Notably, in contrast to the
clinically validated scoring criteria for gastroesophageal carcinoma
established by the TOGA trial for Herceptin therapy, these authors deliberately
applied more traditional HER2 scoring criteria that are established for breast
cancer.  <\/span><\/p>

They evaluated 135 paraffin
embedded advanced gastroesophageal carcinomas from the pathology files of
Memorial Sloan Kettering Cancer Center<\/a> by HER2 automated immunohistochemistry
using PATHWAY Rabbit Monoclonal Antibody 4B5 on a Ventana BenchMark stainer
and, by HER2 FISH using the Path Vision dual probe procedure.  <\/span><\/p>

Again, in this study, both ICH
and FISH were interpreted using criteria for breast cancer per the 2007 ASCO
CAP scoring guidelines.  By ASCO CAP
guidelines, 16 of 16 or 100% of the IHC 3+ tumors were FISH amplified; 16 of 20
or 80% of FISH amplified tumors were IHC 3+. 
<\/span><\/p>

Overall, IHC FISH concordance
was 97% for IHC 0 tumors, 93% for IHC 1+ tumors and 100% for IHC 3+ tumors—all
very high concordance rates—but note, that I have not described the FISH IHC
concordance rate for equivocal IHC 2+ tumors. 
Among this group of 8 equivocal IHC 2+ tumors, three were amplified,
four unamplified, and one equivocal indicating a roughly 50% concordance
rate.  <\/span><\/p>

Finally, the authors
reclassified their IHC and FISH scoring using modified TOGA clinical trial criteria
and obtained a similar but no identical concordance rate.  From this, the authors conclude that HER2
testing in gastroesophageal cancers can be performed using 2007 ASCO CAP
scoring guidelines for breast cancer. 
Think about it.  I do not think
that such a bold conclusion is supported by this work.  <\/span><\/p>

In their discussion, the
authors also state that for gastroesophageal cancers IHC 1+ and 2+ results should
be resolved by what they call definitive FISH testing.  Both this statement and the conclusion that
we can apply breast cancer scoring criteria are not supported by any clinical
evidence.  <\/span><\/p>

In fact, the TOGA clinical
trial data contradict the notion that FISH results are in any way more
definitive or more predictive than IHC results. 
The TOGA clinical trial data actually suggests that for gastroesophageal
cancers, IHC results are more predictive of drug response.  <\/span><\/p>

The authors have done a large
amount of work and report very good correlation between PATHWAY Ventana
immunohistochemistry HER2 testing and Path Vision FISH results in
gastroesophageal cancer but as far as I can tell that is all.  I have yet to see any clinical
evidence—certainly not in this paper—to support their suggestion that ASCO CAP
breast cancer scoring is acceptable or that FISH HER2 results are the
definitive answer for gastric cancers.  <\/span><\/p>

I hope that this is not the
beginning of numerous laboratory correlation studies on HER2 testing on gastric
or other types of cancer that lack clinical outcome data but spawn speculative
conclusions about clinical utility.  One
suggestion I would make if it has not already been done is to retrospectively
score TOGA clinical trial gastroesophageal cancers by ASCO CAP breast cancer
criteria and see which system best predicted drug response.  <\/span><\/p>

Short of that effort, someone
would have to essentially repeat the TOGA trial to truly answer the question
posed by these authors.  <\/span><\/p>

To my knowledge and for now,
the modified TOGA scoring criteria for gastroesophageal cancer HER2 status
remain uniquely validated by a clinical trial. 
<\/span><\/p>

Biologically, it seems
imprudent to expect standards for HER2 testing in breast cancer to translate
simply and unchanged across primary and anatomic sites from breast to stomach
to lung or any other organ.  That is not
the case for anti-EGFR drug modality or laboratory testing algorithms in lung
and colon cancers which have benefited from quite different anti-EGFR drugs and
laboratory testing strategies.  In lung
cancer, use of anti- HER2 therapies is currently investigative but already
there is some published literature indicting that HER2 gene mutation status
(not protein over expression and not gene amplification) may identify the
subset of lung cancer patients who respond to Herceptin.  <\/span><\/p>

The name of the game is predicting
drug response and that requires empirical clinical outcome data.<\/span><\/p>

 <\/p><\/div>

<\/a> <\/a> <\/a> <\/a> <\/a> <\/a> <\/a> <\/a><\/div>

Source:
http:\/\/feeds.feedburner.com\/DigitalPathologyBlog<\/a><\/p>","protected":false},"excerpt":{"rendered":"

Review of: Tafe, LJ, JanjiigianYY, Zaidinski M, et al.  Human EpidermalGrowth Factor Receptor 2 Testing in Gastroesophageal Cancer Correlation BetweenImmunohistochemistry and Fluorescence In Situ Hybridization.  Arch Pathol Lab Med; 2011;135:1460-1465.Experienced pathologists arefamiliar with the bumpy and often controversial evolution of … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":57,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"limit_modified_date":"","last_modified_date":"","_lmt_disableupdate":"","_lmt_disable":"","footnotes":""},"categories":[577487],"tags":[],"class_list":["post-246179","post","type-post","status-publish","format-standard","hentry","category-pathology"],"modified_by":null,"_links":{"self":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts\/246179"}],"collection":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/users\/57"}],"replies":[{"embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/comments?post=246179"}],"version-history":[{"count":0,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts\/246179\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/media?parent=246179"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/categories?post=246179"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/tags?post=246179"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}