Sorted By Test Name - Mayo Medical Laboratories

FHER2
81954
Treat 1997 43:87-95. Molina R, Jo J, Fiella et al., c-erb-2 oncoprotein in the sera and tissue of patients
with breast cancer: Utility in prognosis. Anti- cancer Research 1996 16:2295-2300.
HER2 Amplification Associated with Breast Cancer, FISH,
Tissue
Clinical Information: HER2 (ERBB2: c-erb-b2) is an oncogene on the long arm of chromosome 17
that is amplified in approximately 20% of breast cancers.(1) Amplification or overexpression of HER2
has been shown to be associated with shorter disease-free survival and poorer overall survival in both
node-negative and node-positive ductal breast cancers.(1) Patients with HER2 gene amplification or
overexpression appear to respond better to cyclophosphamide/doxorubicin/5-fluorouracil (CAF)
chemotherapy than patients whose tumors do not exhibit HER2 amplification or overexpression HER2
amplified patients are candidates for treatment with the drug Herceptin (trastuzumab).(8) FISH with
labeled DNA probes to the pericentromeric region of chromosome 17 and to the HER2 locus can be used
to determine if a patient's breast cancer has HER2 gene amplification.(2-4) Immunohistochemical analysis
is used to determine if a tumor exhibits HER2 overexpression.(1) FISH has been shown to be superior to
Southern, Northern, and Western blots and immunohistochemical analyses for the determination of HER2
amplification in formalin-fixed, paraffin-embedded material.(2,3) HER2 amplification as detected with
FISH has been shown to be an independent predictor of poor clinical outcome.(5)
Useful For: As a prognostic indicator for patients with both node-positive or node-negative breast
cancer(1) To guide therapy, as patients with HER2 amplification may be candidates for Herceptin
therapy(1) To confirm the presence of HER2 amplification in cases with 2+ (low-level) or 3+ (high-level)
HER2 overexpression by immunohistochemistry(2,3)
Interpretation: An interpretive report is provided. Results are interpreted utilizing the 2007 American
Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.(6) Specimens
with equivocal results (see Method Description) require repeat FISH analysis per ASCA/CAP guidelines.
The degree of HER2 amplification varies in tumors. Some exhibit high levels of amplification
(HER2:CEP17 ratio >4.0), whereas others exhibit low-level amplification (HER2:CEP17 ratio of 2.2-4.0).
It is not currently known if patients with different levels of amplification have the same prognosis and
response to therapy. Reports also interpret the HER2 copy number changes relative to chromosome 17
copy number (aneusomy) or potential structural changes that increase HER2 copy number. Rare cases
may not show HER2 amplification but still have HER2 protein overexpression demonstrated by
immunohistochemistry(2). The clinical significance of HER2 overexpression in the absence of HER2
gene amplification is unclear. However, these patients may have a worse prognosis and be candidates for
Herceptin treatment.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Pegram MD, Pauletti G, Slamon DJ: HER-2/neu as a predictive marker of
response to breast cancer therapy. Breast Cancer Res Treat 1998;52:65-77 2. Pauletti G, Godolphin W,
Press MF, Slamon DJ: Detection and quantitation of HER-2/neu gene amplification in human breast
cancer archival material using fluorescence in situ hybridization. Oncogene 1996;13:63-72 3. Press MF,
Hung G, Godolphin W, Slamon DJ: Sensitivity of HER-2/neu antibodies in archival tissue specimens:
potential source of error in immunohistochemical studies of oncogene expression. Cancer Res
1994;54:2771-2777 4. Masood S, Bui MM, Yung JF, et al: Reproducibility of LSI HER-2/neu
SpectrumOrange and CEP 17 SpectrumGreen dual color deoxyribonucleic acid probe kit. For
enumeration of gene amplification in paraffin-embedded specimens: a multicenter clinical validation
study. Ann Clin Lab Sci 1998;28:215-223 5. Press MF, Bernstein L, Thomas PA, et al: HER-2/neu gene
amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast
carcinomas. J Clin Oncol 997;15:2894-2904 6. Wolff AC, Hammond ME, Schwartz JN, et al: American
Society of Clinical Oncology/College of American Pathologists Guideline recommendations for human
epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007 Jan;131(1):18-43
7. Perez EA, Roche PC, Jenkins RB, et al: HER2 testing in patients with breast cancer: poor correlation
between weak positively by immunohistochemistry and gene amplification by fluorescence in situ
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