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Randomized Controlled Trial
. 2014 Nov 11;111(10):1977-84.
doi: 10.1038/bjc.2014.483. Epub 2014 Sep 11.

HER2/neu testing in primary colorectal carcinoma

B Ingold Heppner  1 , H-M Behrens  2 , K Balschun  2 , J Haag  2 , S Krüger  2 , T Becker  3 , C Röcken  2
Affiliations
Randomized Controlled Trial

HER2/neu testing in primary colorectal carcinoma

B Ingold Heppner et al. Br J Cancer. .

Abstract

Background: Anti-HER2/neu therapy is well-established in breast and gastric carcinoma. The increased understanding of this pathway led to the identification of new promising drugs in addition to trastuzumab, offering further perspectives. The role of HER2/neu in colorectal carcinoma is controversially discussed, as discrepant data has been reported.

Methods: Here, we retrospectively assessed the prevalence of HER2/neu positivity in a large series of colorectal carcinoma, testing HER2/neu status according to current recommendations. We correlated the results to clinico-pathological data and patient survival.

Results: Overall, in 1645 primary colorectal carcinoma cases, 1.6% of the cases were HER2/neu positive. HER2/neu positivity significantly correlated with higher UICC stages (P=0.017) and lymph node metastases (P=0.029). In the subgroup of sigmoideal and rectal carcinomas, positive HER2/neu status was associated with T-category (P=0.041) and higher UICC stages (P=0.022). Although statistically not significant, HER2/neu-positive colorectal carcinomas displayed a tendency to poorer overall survival.

Conclusions: These results illustrate the importance of testing HER2/neu by approved diagnostic techniques and scoring systems. We assume that although the prevalence of HER2/neu positivity in colorectal carcinoma is low, HER2/neu testing in advanced, nodal-positive colorectal carcinoma is reasonable, offering a potential target in high risk colorectal carcinoma.

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Figures

Figure 1
Figure 1
HER2/neu immunoreactivity. Colorectal carcinoma samples displaying absent (score 0; A), weak (score 1+, B), moderate (score 2+, C) or strong (score 3+, D) HER2/neu membrane staining according to the magnification rule of current HER2/neu-testing guidelines in gastric cancer. Whole tissue section of a CRC sample showing a ‘black-and-white' HER2/neu expression and corresponding TMA punch areas (E, F). Scale bars: A–D, 50 μm; E, 500 μm; F, 200 μm.
Figure 2
Figure 2
HER2/neu in situ hybridisation. Analysis of HER2/neu amplification by dual-color chromogenic in situ hybridisation (CISH) using HER2/neu (green) and chromosome 17 enumeration probes (red) revealing colorectal carcinoma negative (A) and positive (B) for HER2/neu amplification. Genetically heterogeneous sample examined by IHC (C) and CISH (D). Scale bar: A–D, 50 μm.
Figure 3
Figure 3
Primary colorectal carcinoma (A, B) and corresponding lymph node metastasis (C, D) showing the identical HER2/neu status in IHC (A, C) as well as in CISH (B, D). Scale bar: A–D, 50 μm.
Figure 4
Figure 4
Overall survival. Kaplan–Meier curve depicting a tendency to poorer overall survival in HER2/neu-positive colorectal carcinoma.
See this image and copyright information in PMC

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