J Korean Med Sci.  2008 Dec;23(6):1053-1061. 10.3346/jkms.2008.23.6.1053.

Comparison of Her-2, EGFR and Cyclin D1 in Primary Breast Cancer and Paired Metastatic Lymph Nodes: An Immunohistochemical and Chromogenic In Situ Hybridization Study

• Cho EY
• Han JJ
• Choi YL
• Kim KM
• Oh YL

• KMID: 1107533
• DOI: http://doi.org/10.3346/jkms.2008.23.6.1053

Abstract

The significant advance in the development of molecular-targeting drugs has made an evaluation of Her-2, EGFR, and cyclin D1 an important clinical issue in breast cancer patients. This study compared the Her-2, EGFR, and cyclin D1 status of primary tumors as well as their matching lymph node metastases using immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) in 73 breast cancer patients. Her-2, EGFR, and cyclin D1 protein showed a concordance between the primary lesion and the metastatic regional lymph nodes in 82%, 90%, and 63%, respectively. CISH also revealed 92%, 93%, and 85% concordance in the gene amplification status of Her-2, EGFR, and cyclin D1, showing a reasonable agreement between primary tumors and metastatic regional lymph nodes. Although a statistically significant agreement was found in Her-2 expression, a relatively high discordance rate (18%) raises a little concern. Our findings suggest that the Her-2 status can be reliably assessed on primary tumor but a possible difference can be found in Her-2, EGFR, and cyclin D1 status between the primary and the metastatic sites and this possibility should be concerned in patients considering molecular targeted therapy or patients with progress of disease.

Keyword

CISH; Her-2; EGFR; Cyclin D1; Immunohistochemistry

MeSH Terms

Adult
Aged
Breast Neoplasms/genetics/*metabolism/pathology
Chromogenic Compounds
Cyclin D1/*analysis/genetics
Female
Humans
Immunohistochemistry
In Situ Hybridization
Lymph Nodes/*metabolism/pathology
Lymphatic Metastasis
Male
Middle Aged
Neoplasm Recurrence, Local/genetics/metabolism
Receptor, Epidermal Growth Factor/*analysis/genetics
Receptor, erbB-2/*analysis/genetics
Survival Analysis

Figure

• 

  Fig. 1 Comparison of immunostaining patterns of Her-2, EGFR and cyclin D1 in primary tumor and the corresponding metastatic lymph node (LN) (×200). 3+/3+ expression of Her-2 in primary tumor (A) and LN (B); 2+/- expression of Her-2 in primary tumor (C) and LN (D); 1+/2+ expression of Her-2 in primary tumor (E) and LN (F), 3+/- expression of EGFR in primary tumor (G) and LN (H); -/2+ expression of EGFR in primary tumor (I) and LN (J); -/3+ expression of cyclin D1 in primary tumor (K) and LN (L).

• 

  Fig. 2 Comparison of gene amplification patterns of Her-2, EGFR and cyclin D1 in primary tumor and the corresponding metastatic lymph node (LN) (×400). High-level amplification/high-level amplification of Her-2 in primary tumor (A) and LN (B); high-level amplification/no amplification of Her-2 in primary tumor (C) and LN (D); high-level amplification/no amplification of EGFR in primary tumor (E) and LN (F); low-level amplification/low-level amplification of EGFR in primary tumor (G) and LN (H); high-level amplification/no amplification of cyclin D1 in primary tumor (I) and LN (J); high-level amplification/high-level amplification of cyclin D1 in primary tumor (K) and LN (L).

• 

  Fig. 3 Recurrence-free survival according to EGFR amplification. Disease-free survival is significantly low in patients with EGFR amplification in primary tumor and no EGFR amplification in metastatic tumor (p=0.0454).

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