Definition / general:
- HER2/neu is the human epidermal growth factor receptor 2, also called ERBB2 (Erb-B2 receptor tyrosine kinase 2)
- HER2 gene encodes transmembrane growth factor receptor (p185)
- Cytoplasmic tyrosine kinase is constitutively active when overexpressed due to homo / heterodimerization (International Seminars in Surgical Oncology 2008;5:9)
- The biologic impact of HER2 gene amplification is not due to (a) mere chromosome 17 polysomy without HER2 gene amplification (Am J Surg Pathol 2005;29:1221) or (b) chromosome 17 aneusomy
- Aneusomy means other than 2 copies of chromosome (Mod Pathol 2002;15:137)
Terminology:
- Also called Human Epidermal growth factor Receptor 2, c-erbB2, neu, ERBB2, CD340
Clinical features:
- Present in approximately 15 – 20% of breast tumors
- Associated with comedocarcinoma and aggressive invasive tumors
- Usually appears first in ADH or DCIS (Mod Pathol 2002;15:116)
- Also seen in non breast cancers (Mod Pathol 2007;20:192)
- Anti-HER2 therapy (trastuzumab / Herceptin®) plus chemotherapy reduces recurrence, metastases and mortality in HER2 gene amplified breast cancer patients (Int Semin Surg Oncol 2008;5:9, Acta Oncol 2008;47:1564); Lapatinib (Tykerb®) has a similar effect (Biologics 2009;3:289)
- Anti-HER2 therapy may improve survival in metastatic disease (Am J Clin Oncol 2008;31:250, N Engl J Med 2007;357:1496) but is associated with cardiac toxicity (BMC Cancer 2007;7:153)
- To detect, the most commonly used in situ hybridization (ISH) is a dual probe fluorescent ISH (FISH) using fluorochrome labeled probes for (a) the HER2 locus on the long arm of chromosome 17 and (b) a site near the centromere of chromosome 17 (CEN17 or CEP17)
- In situ hybridization detects HER2 gene amplification as evaluated by counting at least 20 tumor cells and estimating the HER2 copy number and the HER2/CEP17 ratio
- Amplification can also be detected with chromogenic ISH (CISH), (Mod Pathol 2002;15:657, Mod Pathol 2005;18:1015, Mod Pathol 2006;19:481, Breast Cancer Res 2007;9:R68) and silver enhanced ISH (SISH) (Am J Clin Pathol 2009;132:514)
- CISH and SISH use a peroxidase enzyme labeled probe with chromogenic detection, allowing results to be visualized with standard brightfield microscopy, so histologic features and HER2 status can be evaluated in parallel; signals do not decay over time, unlike FISH (Am J Clin Pathol 2009;132:539)
- Chromogenic in situ hybridization (CISH) is the only FDA approved single probe ISH test for HER2
- Quantitative reverse transcription polymerase chain reaction can also be used (Am J Clin Pathol 2008;129:563)
- Immunohistochemistry (IHC) detects evidence of protein overexpression via evaluation of the membranous staining in the tumor cells
- Testing must be performed in accredited laboratories
Sumber:
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