Her2/neu testing in gastric cancer: evaluating the risk of sampling errors

Abstract

BackgroundWe evaluated the risk of sampling errors in specimens of biopsy size, which may be caused by heterogeneous overexpression of Her2/neu in gastric cancer (GC).Patients and methodsThe study cohort comprised 454 gastrectomy patients with adenocarcinoma of the stomach or esophago-gastric junction. Tissue micro-arrays (TMAs) served as ‘biopsy procedure’ and were generated from formalin-fixed and paraffin-embedded tissue: five tissue cylinders were collected randomly from each tumor, rendering 2230 core cylinders. These were compared with 454 whole tissue sections obtained from the same paraffin blocks. Her2/neu expression and gene amplification were analyzed by immunohistochemistry and in situ hybridization. The Her2/neu status was determined according to GC scoring system by two independent observers.ResultsIn whole tissue sections, 37 (8.1%; observer 1) and 38 (8.4%; observer 2) of the GCs, and in the corresponding TMAs, 28 (6.3%; observer 1) and 28 (6.3%; observer 2) of the GCs were classified as Her2/neu-positive (kappa value 98.5% and 96.2%; P < 0001). Comparison of whole tissue sections with corresponding TMAs showed a false-negative rate of 24% and a false-positive rate of 3% for TMAs.ConclusionAssessment of the Her2/neu status in tissue biopsies carries a significant risk of sampling errors, thereby rendering patients unsuitable for treatment with trastuzumab.

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“…For this reason, concerns were previously raised against the use of TMA, in favor of whole tissue sections [14,21,36].…”

Optimal chemotherapy for advanced gastric cancer: is there a global consensus?

“…Testing for HER2 in GC has its pitfalls and challenges. Optimal tumor samples should be used, and testing should be done in well-trained and quality-assured pathology laboratories [55,56]. The greatest benefitof using trastuzumab may be gained by patients with the highest degree of HER2 overexpression: those that are IHC 3?…”

HER2 testing in paired biopsy and excision specimens of gastric cancer: the reliability of the scoring system and the clinicopathological factors relevant to discordance

“…Our current study differs from our previous study in terms of distribution of tumor location, histological type, and tumor differentiation. In our previous study, HER2 IHC was performed in tissue microarrays rather than whole-tissue sections, and this procedural difference may account, at least in part, for the different percentages of HER2-positive cells in the two studies [19,20].…”

“…A possible explanation of HER2 discordance in paired specimens is sample error, which is unavoidable in heterogeneous populations of tumor cells. Warneke et al [20] used tissue microarrays generated from embedded tumor tissue as biopsies. The tissue microarrays resulted in an HER2 false-negative rate of 24 % and an HER2 false-positive rate of 3 %.…”