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. 2016 Apr;19(2):553-560.
doi: 10.1007/s10120-015-0502-3. Epub 2015 May 19.

Five biopsy specimens from the proximal part of the tumor reliably determine HER2 protein expression status in gastric cancer

Naoyuki Tominaga  1   2 , Takuji Gotoda  3 , Megumi Hara  4 , Matthew D Hale  5 , Takayoshi Tsuchiya  3   6 , Jun Matsubayashi  6 , Shin Kono  3 , Chika Kusano  3 , Takao Itoi  3 , Kazuma Fujimoto  7 , Fuminori Moriyasu  3 , Heike I Grabsch  8   9   10
Affiliations

Five biopsy specimens from the proximal part of the tumor reliably determine HER2 protein expression status in gastric cancer

Naoyuki Tominaga et al. Gastric Cancer. 2016 Apr.

Abstract

Background: National guidelines recommend trastuzumab for treatment of patients with metastatic HER2-positive gastric cancer (GC). There is currently no guideline indicating the number of biopsy specimens and the location from which they should be obtained to reliably determine the human epidermal growth factor receptor 2 (HER2) status in GC. The aim of this pilot study was (a) to quantify HER2-positive tumor cells in different tumor regions to assess the spatial heterogeneity of HER2 expression and (b) to establish the required number of biopsy specimens and the location from which they should be obtained within the tumor to achieve concordance between HER2 expression status in the biopsy specimens and the resection specimen.

Methods: HER2 expression was quantified in six different regions of 24 HER2-positive GC and in six virtual biopsy specimens from different luminal regions. Intratumoral regional heterogeneity and concordance between HER2 status in the biopsy specimens and the resection specimen were analyzed.

Results: HER2-positive cells were more frequent in the luminal tumor surface compared with deeper layers (p < 0.001). GCs with differentiated histological features were more commonly HER2 positive (p < 0.001). Assessment of HER2 expression status in five biopsy specimens was sufficient to achieve 100 % concordance between the biopsy specimens and the resection specimen.

Conclusions: This is the first study to suggest preferential HER2 positivity at the luminal surface in GC and to establish a minimum number of biopsy specimens needed to obtain a biopsy HER2 result which is identical to that from the whole tumor. Our study suggests that HER2 testing in five tumor-containing endoscopic biopsy specimens from the proximal (oral) part of the tumor is advisable. The results from this pilot study require validation in a prospective study.

Keywords: Gastric cancer; HER2 expression; Virtual biopsy.

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Figures

Fig. 1
Fig. 1
The division of the tumor into six parts. The tumor was divided equally into three regions—oral region (O), central region (M), and anal region (A)—which were each divided in turn into an upper layer (LUM) and a lower layer (DEEP)
Fig. 2
Fig. 2
The “virtual biopsy.” We marked six positions on the prepared slide by a double-blind method: two were on the surface of the oral region (O), two were on the surface of the central region (M), and two were on the surface of the anal region (A). The black dots in the image at the bottom right indicate the tumor range (the tumor area was inside). The virtual biopsy sites are indicated by white circles. HE hematoxylin and eosin, HER2 human epidermal growth factor receptor 2
Fig. 3
Fig. 3
Human epidermal growth factor receptor 2 expression ratio related to the number of biopsy specimens
Fig. 4
Fig. 4
The result of Holm’s test for cells expressing human epidermal growth factor receptor 2 which were counted individually. A anal region, DEEP deeper layer, LUM luminal layer, M central region, O oral region
See this image and copyright information in PMC

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