Are biopsy specimens predictive of HER2 status in gastric cancer patients?
BACKGROUND
Trastuzumab has been recently proposed as a treatment for patients with HER2-positive advanced/metastatic gastric cancer (GC). Since most patients have inoperable disease at diagnosis, accurate assessment of HER2 status on biopsy specimens is essential to select the patients who may benefit from therapy.


OBJECTIVE
The aim of this study is to establish whether HER2 status assessed on biopsy material could be reliable for treatment decisions using anti-HER2 agents.


METHODS
The HER2 status was evaluated in 61 consecutive pairs of biopsy and surgical GCs samples by immunohistochemistry and chromogenic in situ hybridization.


RESULTS
The overall concordance of HER2 status between biopsy and surgical specimens was 91.8 % with a predictive positive value of 71.4 % and a negative predictive value of 94.4 %. Of five discordant cases, there were three negative and two positive false biopsy results. All the false negative cases showed heterogeneous expression of HER2 protein in surgical samples. Two cases displayed overexpression of the receptors without corresponding gene amplification.


CONCLUSIONS
HER2 status as evaluated on biopsy samples is a fairly good predictor of HER2 status of surgically-excised GCs. The most important influence for discordant results is tumor heterogeneity. However, HER2 overexpression, especially without coexisting gene amplification, may only be a temporary change in a tumor population. This may explain those cases with positive HER2 evaluation on biopsy material and a negative result on corresponding surgical specimen.
Department of Pathology, Scientific Institute for Digestive Diseases S de Bellis, via Turi 27, Castellana Grotte, BA, Italy. michelepirrelli@libero.it
M
M
Pirrelli
M L
ML
Caruso
M
M
Di Maggio
R
R
Armentano
A M
AM
Valentini
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001706:Biopsy / Q000379:methods* / Q000592:standards; D005188:False Negative Reactions; D005189:False Positive Reactions; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods / Q000592:standards; D017403:In Situ Hybridization / Q000379:methods / Q000592:standards; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human