J Korean Med Sci.  2011 Aug;26(8):1001-1006. 10.3346/jkms.2011.26.8.1001.

Evaluation of Intratumoral HER-2 Heterogeneity by Fluorescence In Situ Hybridization in Invasive Breast Cancer: A Single Institution Study

• Lee S
• Jung W
• Hong SW
• Koo JS

• KMID: 1777837
• DOI: http://doi.org/10.3346/jkms.2011.26.8.1001

Abstract

This study aimed to determine the incidence and characteristics of HER-2 gene heterogeneity in invasive breast cancer in a single institution. Included were 971 cases of primary invasive breast cancer diagnosed between 2008 and 2010. Fluorescence in situ hybridization (FISH) image files were retrospectively reviewed and HER-2 gene heterogeneity was defined as more than 5% but less than 50% of analyzed invasive tumor cells with a HER-2/Chr17 ratio higher than 2.2, according to the College of American Pathologists guidelines. HER-2 gene heterogeneity was identified in 24 (2.5%) cases. The mean proportion of invasive tumor cells with a HER-2/chromosome 17 ratio higher than 2.2 was 11.6% (range: 5%-25%). Of 24 cases, HER-2 gene status was not amplified in 8, showed borderline amplification in 2, and amplification in 14. All HER-2 amplification cases were low-grade. In conclusion, HER-2 gene heterogeneity of invasive breast cancer is identified in routine FISH examination. This may affect the results of HER-2 gene amplification status in FISH studies.

Keyword

Breast Neoplasms; HER-2; Gene Heterogeneity; In Situ Hybridization, Fluorescence

MeSH Terms

Adult
Breast Neoplasms/*genetics/pathology
Chromosomes, Human, Pair 17
Female
Genetic Heterogeneity
Humans
In Situ Hybridization, Fluorescence/*methods
Middle Aged
Receptor, erbB-2/*genetics/metabolism
Retrospective Studies

Figure

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  Fig. 1 Breast cancer with HER-2 gene heterogeneity. The histology of breast cancer with HER-2 gene heterogeneity is invasive ductal carcinoma (H&E, × 100, A-C). Immunohistochemical stain for HER-2 shows heterogeneous 3+ overexpression (arrows, HER-2, × 200, D-F). Fluorescence in situ hybridization study shows heterogeneous invasive tumor cells with a HER-2/Chr17 ratio higher than 2.2 (arrow, × 1,000, G-I).

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  Fig. 2 Correlation between proportion of invasive tumor cells with a HER-2/Chr17 ratio higher than 2.2 and HER-2 amplification index.

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  Fig. 3 Proportion of invasive tumor cells with a HER-2/Chr17 ratio higher than 2.2 according to HER-2 gene status.

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