Stains & Molecular markers HER2 (c-erbB2) breast

Admin/ May 31, 2021/ Flexylabs Info

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:
pathologyoutlines.com/topic/stainsbreasther2.html

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