FP-001: Human HER2 gene amplification detection kit

HER2 Gene Amplification: Overview

HER2 (Human Epidermal Growth Factor Receptor 2) gene amplification is a major oncogenic driver in multiple cancers, most notably in 15-20% of breast cancers (HER2-positive breast cancer). It is a classic example of a gene copy number alteration leading to cancer development and progression.

Core Mechanism

• Definition: A genetic abnormality where the ERBB2 gene (located on chromosome 17q12) is duplicated multiple times, leading to overexpression of the HER2 protein on the cell surface.

• Result: 25-50+ copies of the gene (vs. 2 in normal cells), causing 10-100x more HER2 receptor proteins per cell.

• Consequence: Massive signal amplification → uncontrolled activation of downstream pathways (PI3K/AKT, MAPK) → increased cell proliferation, survival, migration, and inhibition of apoptosis

Clinical Significance

1. In Breast Cancer

• Prevalence: ~20% of invasive breast cancers.

• Prognosis: Historically associated with aggressive disease, higher recurrence risk, and poorer survival (prior to targeted therapies).

• Therapeutic Target: The paradigm for successful targeted therapy.

  • Monoclonal Antibodies: Trastuzumab, Pertuzumab, Margetuximab.

  • Antibody-Drug Conjugates (ADCs): T-DM1 (ado-trastuzumab emtansine), T-DXd (trastuzumab deruxtecan).

  • Tyrosine Kinase Inhibitors (TKIs): Lapatinib, Tucatinib, Neratinib.

2. In Other Cancers

• Gastric/Gastroesophageal Junction (GEJ) Adenocarcinoma: ~10-20% incidence; HER2-targeted therapy is standard.

• Colorectal Cancer: ~3-5% incidence; emerging target.

• Other Cancers: Reported in subsets of bladder, ovarian, lung, and biliary tract cancers.

Detection Methods

1. Immunohistochemistry (IHC): Measures HER2 protein overexpression.

   • Scores: 0, 1+ (negative), 2+ (equivocal), 3+ (positive).

2. Fluorescence In Situ Hybridization (FISH): Gold standard for detecting gene copy number.

   • Positive: HER2/CEP17 ratio ≥2.0 with average HER2 copy number ≥4.0 signals/cell.

3. Chromogenic In Situ Hybridization (CISH/SISH): Alternative to FISH.

4. Next-Generation Sequencing (NGS): Can detect amplification via copy number variation analysis.

Therapeutic Implications & Resistance

• Success Story: HER2-targeted therapies dramatically improved outcomes in HER2+ breast cancer, turning it from a poor prognosis to a highly treatable subtype.

• Primary Resistance: Some tumors do not respond initially (e.g., PIK3CA mutations, PTEN loss).

• Acquired Resistance: Mechanisms include:

  • Alterations in downstream pathways.

  • HER2 extracellular domain mutations.

  • Upregulation of alternative receptors (e.g., HER3, c-MET).

Current Trends & Research

• HER2-Low Concept: Tumors with IHC 1+ or 2+/FISH-negative (~50% of breast cancers) may still benefit from newer ADCs.

• Novel ADCs: Redefining treatment in both HER2-positive and HER2-low cancers.

• Combination Therapies: With immunotherapy, CDK4/6 inhibitors, or other targeted agents.

• Early Detection & Monitoring: Using liquid biopsy (ctDNA) to track amplification and resistance.

Key Takeaway

HER2 gene amplification is a critical biomarker that defines a distinct molecular subtype of cancer, guides targeted therapy, and remains a cornerstone of precision oncology. Its discovery and the subsequent development of HER2-targeted therapies represent one of the most successful translations of basic cancer biology into clinical practice.

[Instructions Manual] Human HER2 gene amplification detection kit