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PathVysion
For In Vitro Diagnostic Use

Product Probe Description

Probe Name Probe Location Fluorophore
Vysis LSI HER-2/neu 17q11.2-12 SpectrumOrange
Vysis CEP 17 17p11.1-q11.1 Alpha Satellite DNA SpectrumGreen

Product Description

Intended Use

The PathVysion HER-2 DNA Probe Kit (PathVysion Kit) which is FDA approved is designed to detect amplification of the HER-2/neu gene via fluorescence in situ hybridization (FISH) in formalin-fixed, paraffin-embedded human breast cancer tissue specimens. Results from the PathVysion Kit are intended for use as an adjunct to existing clinical and pathologic information currently used as prognostic factors in stage II, node-positive breast cancer patients. The PathVysion Kit is further indicated as an aid to predict disease-free and overall survival in patients with stage II, node positive breast cancer treated with adjuvant cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) chemotherapy.

The PathVysion Kit is indicated as an aid in the assessment of patients for whom HERCEPTIN (Trastuzumab) treatment is being considered (see HERCEPTIN package insert).

HER-2/neu, also known as c-erbB2 or HER-2, is a gene that has been shown to play a key role in the regulation of cell growth. The gene codes for a 185 kd transmembrane cell surface receptor that is a member of the tyrosine kinase family. HER-2 has been shown to be amplified in human breast, ovarian, and other cancers.

Warning

The Vysis PathVysion Kit is not intended for use to screen for or diagnose breast cancer. It is intended to be used as an adjunct to other prognostic factors currently used to predict disease-free and overall survival in stage II, node-positive breast cancer patients. In making decisions regarding adjuvant CAF treatment, all other available clinical information should also be taken into consideration, such as tumor size, number of involved lymph nodes, and steroid receptor status.No treatment decision for stage II, node-positive breast cancer patients should be based on HER-2/neu gene amplification status alone.

The PathVysion HER-2 DNA Probe Kit consists of two labeled DNA probes. The LSI HER-2 probe that spans the entire HER-2 gene is labeled in SpectrumOrange. The CEP 17 probe is labeled in SpectrumGreen and hybridizes to the alpha satellite DNA located at the centromere of chromosome 17 (17p11.1-q11.1). Inclusion of the CEP 17 probe allows for the relative copy number of the HER-2 gene to be determined.


Results of Hybridization

Results on enumeration of 20 interphase nuclei from tumor cells per target are reported as the ratio of average HER-2/neu copy number to that of CEP 17. Our clinical study found that specimens with amplification showed a LSI HER-2/neu and CEP 17 signal ratio of greater than or equal to 2.0; normal specimens showed a ratio of less than 2.0. Results at or near the cut-off point (1.8-2.2) should be interpreted with caution.

Hybridization Normal

PathVysion HER-2 DNA Probe Kit hybridized to breast tissue showing multiple copies of the HER-2 gene as represented by multiple orange signals. The ratio of orange to green probe signals is greater than 2.0 indicating HER-2 amplification.

Probe Map

Probe Map


Ideogram

Ideogram

  1. Bianco, A.R., et al. (1998) Proceedings of the 37th Annual Meeting of ASCO p. 17, Abstract no. 373.
  2. Clark, G.M., et al. (1998) J Nat Cancer Inst 90, 1320-1.
  3. Coussens, L., et al. (1985) Science 230, 1132-9.
  4. Ishikawa, T., et al. (1997) Am J Pathol 151, 761-8.
  5. Muss, H.B., et al. (1994) N Engl J Med 330, 1260-6.
  6. Pauletti, G., et al. (1998) Proceedings of the 89th Annual Meeting of AACR p. 39, Abstract no. 345.
  7. Press, M.F., et al. (1990) Prog Clin Biol Res 354A, 209-21.
  8. Press, M.F., et al. (1994) Cancer Res 54, 2771-7.
  9. Slamon, D.J., et al. (1987) Science 235, 177-82.
  10. Slamon, D.J., et al. (1989) Science 244, 707-12.
  11. Wiltschke, C., et al. (1994) J Cancer Res Clin Oncol 120, 737-42.
 

Intended Use
The PathVysion HER-2 DNA Probe Kit (PathVysion Kit) is designed to detect amplification of the HER-2/neu gene via fluorescence in situ hybridization (FISH) in formalin-fixed, paraffin-embedded human breast cancer tissue specimens. Results from the PathVysion Kit are intended for use as an adjunct to existing clinical and pathologic information currently used as prognostic factors in stage II, node-positive breast cancer patients. The PathVysion Kit is further indicated as an aid to predict disease-free and overall survival in patients with stage II, node-positive breast cancer treated with adjuvant cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) chemotherapy.

The PathVysion Kit is indicated as an aid in the assessment of patients for whom HERCEPTIN (Trastuzumab) treatment is being considered (see HERCEPTIN package insert).

 

Warning:
HERCEPTIN therapy selection
NOTE: All of the patients in the HERCEPTIN clinical trials were selected using an investigational immunohistochemical assay (CTA). None of the patients in those trials were selected using the PathVysion assay. The PathVysion assay was compared to the CTA on a subset of clinical trial samples and found to provide acceptably concordant results. The actual correlation of the PathVysion assay to HERCEPTIN clinical outcome in prospective clinical trials has not been established.
Adjuvant therapy selection
The PathVysion Kit is not intended for use to screen for or diagnose breast cancer. It is intended to be used as an adjunct to other prognostic factors currently used to predict disease-free and overall survival in stage II, node-positive breast cancer patients and no treatment decision for stage II, node-positive breast cancer patients should be based on HER-2/neu gene amplification status alone. Selected patients with breast cancers shown to lack amplification of HER-2/neu may still benefit from CAF (cyclophosphamide, doxorubicin, 5-fluorouracil) adjuvant therapy on the basis of other prognostic factors that predict poor outcome (e.g. tumor size, number of involved lymph nodes, and hormone receptor status). Conversely, selected patients with breast cancers shown to contain gene amplification may not be candidates for CAF therapy due to preexisting or intercurrent medical illnesses. Required Training
Abbott Molecular will provide training in specimen preparation, assay procedure, and interpretation of FISH testing of the Her-2 gene for inexperienced users. It is also recommended that a laboratory that has previously received training but now has new personnel performing the assay request training for the new users.

 

Limitations

  1. The PathVysion Kit has been optimized only for identifying and quantifying chromosome 17 and the HER-2/neu gene in interphase nuclei from formalin-fixed, paraffin-embedded human breast tissue specimens. Other types of specimens or fixatives should not be used.
  2. The performance of the PathVysion Kit was validated using the procedures provided in the package insert only. Modifications to these procedures may alter the performance of the assay.
  3. Performance characteristics of the PathVysion Kit have been established only for node positive patients receiving the designated regimens of CAF and for metastatic breast cancer patients being considered for HERCEPTIN therapy. Performance with other treatment regimens has not been established.
  4. The clinical interpretation of any test results should be evaluated within the context of the patient's medical history and other diagnostic laboratory test results.
  5. FISH assay results may not be informative if the specimen quality and/or specimen slide preparation is inadequate. Technologists performing the FISH signal enumeration must be capable of visually distinguishing between the orange and green signals.

CAUTION: United States Federal law restricts this device to sale and distribution to or on the order of a physician or to a clinical laboratory; use is restricted to, by, or on the order of a physician.

For In Vitro Diagnostic Use