Test Id : HERMB

Cases that are equivocal (2+) by immunohistochemical stain will reflex to HER2 amplification by fluorescence in situ hybridization at an additional charge.

For gastroesophageal cancer, order HERGM / HER2, Gastric/Esophageal, Semi-Quantitative Immunohistochemistry, Manual or HERGN / HER2, Gastric/Esophageal, Semi-Quantitative Immunohistochemistry, Manual, No Reflex.

Attach the green "Attention Pathology" address label (T498) to the outside of the transport container before putting into the courier mailer.

1. An accompanying pathology report stating the final diagnosis is required. If not available, a preliminary diagnosis is acceptable only if it refers to invasive or metastatic breast carcinoma.

2. Information regarding fixative used, time to fixation, and duration of fixation as well as tumor type and classification is required.

The following questions, as stated on the Pathology/Cytology Information (T707) form or presented electronically, must be answered:

 a. "Was specimen fixed in 10% neutral buffered formalin within 1 hour from surgical collection time? Yes, No, or Unknown."

 b. "Has specimen been fixed in 10% neutral buffered formalin for 6 to 72 hours? Yes, No, or Unknown."

 c. "Was tissue decalcified? Yes, No or Unknown."

 d. "Tumor type? Primary invasive breast carcinoma or metastatic breast carcinoma."

 e. "Tumor classification? Invasive breast carcinoma, metastatic breast carcinoma, or micro-invasive breast carcinoma."

Supplies: Pathology Packaging Kit (T554)

Specimen Type:

Preferred: A paraffin-embedded tissue block containing breast cancer tissue that has been fixed in 10% neutral buffered formalin within 1 hour from surgical collection time and for a total of 6 to 72 hours.

Acceptable: 5 Unstained sections containing breast carcinoma on charged slides cut at 4 microns less than 1 month ago. Tissue on the slides should have been fixed in 10% neutral buffered formalin within 1 hour from surgical collection time and for a total of 6 to 72 hours.

Container/Tube: Pathology Packaging Kit

Collection Instructions: Submit paraffin-embedded invasive or metastatic breast carcinoma tissue.

Additional Information:

1. According to the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines, HER2 protein immunohistochemical test results are only valid for nondecalcified, paraffin-embedded specimens fixed in 10% neutral buffered formalin within 1 hour from surgical collection time and for a total time of 6 to 72 hours. Delay to fixation, or under- or over-fixation may affect these results.(1)

2. HER2 immunohistochemistry testing on intracystic papillary carcinoma and solid papillary carcinoma, without clearly stating invasive carcinoma, is not appropriate and will be reported as indeterminate.

3. Paraffin blocks will be returned with final report.

• Pathology/Cytology Information

If not ordering electronically, complete, print, and send with the specimen:

1. Pathology/Cytology Information (T707) is required if not ordering electronically.

2. Immunohistochemical (IHC)/In Situ Hybridization (ISH) Stains Request (T763)

Determining overexpression of HER2 protein on formalin-fixed, paraffin-embedded tissue sections

Cases that are equivocal (2+) by immunohistochemical stain will reflex to HER2 amplification by fluorescence in situ hybridization at an additional charge.

The HER2 (official gene name ERBB2) proto-oncogene encodes a membrane receptor with tyrosine kinase activity and homology to the epidermal growth factor receptor. Amplification and overexpression of the HER2 gene in human breast, endometrial, ovarian, and other epithelial cancers have been associated with a shorter disease-free interval and shorter overall survival. Overexpression of HER2 protein is an indication for Herceptin (trastuzumab) therapy in patients with breast cancer.

This test is most frequently used to evaluate HER2 overexpression in breast cancer.

Reported as negative (0, 1+), equivocal (2+), and strongly positive (3+) according to the interpretation guidelines for the US Food and Drug Administration-approved Ventana Pathway HER2 (4B5) antibody.

Results are reported as negative (0, 1+), equivocal (2+), and strongly positive (3+) according to the published American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) interpretation guidelines.(1)

The performance and quality of immunohistochemical stains in formalin-fixed, paraffin-embedded tissue depends critically on proper fixation.

1. Wolff AC, Hammond ME, Hicks DG, et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018;36(20):2105-2122 doi:10.1200/JCO.2018.77.8738

2. Riber-Hansen R, Vainer B, Steiniche T. Digital image analysis: a review of reproducibility, stability and basic requirements for optimal results. Apmis. 2012;120(4):276-289

3. Gavrielides MA, Gallas BD, Lenz P, Badano A, Hewitt SM.: Observer variability in the interpretation of HER2/neu immunohistochemical expression with unaided and computer-aided digital microscopy. Arch Pathol Lab Med. 2011;135(2):233-242

4. Cuadros M, Villegas R. Systematic review of HER2 breast cancer testing. Appl Immunohistochem Mol Morphol. 2009;17(1):1-7

5. Nassar A, Cohen C, Agersborg SS, et al. Trainable immunohistochemical HER2/neu image analysis: a multisite performance study using 260 breast tissue specimens. Arch Pathol Lab Med. 2011;135(7):896-902

Testing is performed using US Food and Drug Administration-approved Ventana Pathway HER2 (4B5) rabbit monoclonal primary antibody and a proprietary detection system, using modified manufacturer’s instructions.(Package insert: PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody. Ventana Medical Systems, Inc; 09/2022)

Scoring is performed according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as follows:

Score of 3+ is defined as circumferential membrane staining that is complete, intense and in greater than 10% of invasive tumor cells.

Score of 2+ is defined as weak to moderate complete membrane staining observed and in greater than 10% of the invasive tumor cells; or circumferential membrane staining that is complete, intense and in less than or equal to 10% of invasive tumor cells.

Score of 1+ is defined as incomplete membrane staining that is faint or barely perceptible and in greater than 10% of the invasive tumor cells; or weak to moderate complete membrane staining observed and less than 10% of the invasive tumor cells.

Score of 0 is defined as no staining observed or membrane staining that is incomplete and is faint or barely perceptible and in less than or equal to 10% of the invasive tumor cells.(Wolff AC, Hammond ME, Hicks DG, et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018;36(20):2105-2122 doi:10.1200/JCO.2018.77.8738)

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This test has been modified from the manufacturer's instructions. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

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