FISH Score?

[Rich]

My mom has 1.89 on FISH. 5% of nuclei with apparent overexpression. Is this a positive score?

[Lolly]

Rich,
Found an article on Medscape which discusses the FISH test, thought you would find it helpful. Apparently there are now 2 types of FISH testing, so determining whether a score is amplified depends on which method of FISH was used; as if it's not confusing enough!
Below is the reproduced abstract. Hope this helps.





From American Journal of Clinical Pathology

HER-2 Testing in Breast Cancer Using Immunohistochemical Analysis and Fluorescence In Situ Hybridization
Posted 06/09/2004

Priti Lal, MD; Paulo A. Salazar; Clifford A. Hudis, MD; Marc Ladanyi, MD; Beiyun Chen, MD, PhD

Abstract and Introduction
Abstract
We analyzed concordance between immunohisto-chemical analysis and fluorescence in situ hybridization (FISH) in HER-2 status and studied the effect of dual-color (D-FISH) vs single-color FISH (S-FISH) scoring on the assignment of tumors to amplified or nonamplified categories. The assays were performed on formalin-fixed, paraffin-embedded sections of 2,279 invasive breast carcinomas. Immunohistochemical results were interpreted as negative (0, 1+) or positive (2+, 3+). For FISH analyses, a ratio for HER-2/chromosome 17 of 2.0 or more (D-FISH) or an absolute HER-2 copy number per nucleus of more than 4.0 (S-FISH) were interpreted as positive gene amplification.

We found 547 (24.0%) cases positive immunohisto-chemically, 326 (14.3%) by D-FISH, and 351 (15.4%) by S-FISH. Overall concordance in HER-2 status with immunohistochemical analysis was 87% for D-FISH and 86% for S-FISH. Excellent concordance was found among groups scored immunohistochemically as 0, 1+, and 3+ (with D-FISH , 97%; with S-FISH, 96%). The most discordant category was the group scored 2+ immunohistochemically, in which only a quarter of the 2+ tumors were FISH(+). D-FISH and S-FISH scoring results were discordant in 89 tumors (4%), of which 8 (9%) had 3+ immunohistochemical staining and none showed high-level HER-2 amplification. Among all FISH(+) tumors, 10% were negative by immunohisto-chemical analysis, and notably almost half (47%) showed borderline to low HER-2 amplification (D-FISH score, 2.0-3.9); the clinical significance of these findings warrants further investigation.

Introduction
Breast cancer is a disease with highly variable biologic and clinical behavior. Besides the classic prognostic factors used in clinical practice, HER-2 (HER-2/neu, ERBB2), a proto-oncogene located on chromosome 17, has become an important prognostic indicator. Amplification and/or overexpression of HER-2 occur in 15% to 25% of human breast cancers and are associated with a poor clinical outcome.[1-4] With the introduction of trastuzumab (Herceptin, Genentech, South San Francisco, CA), a recombinant "humanized" monoclonal antibody against HER-2 for the treatment of metastatic breast cancer, the accurate assessment of HER-2 status has become essential in determining the clinical management of patients with breast cancer.

Immunohistochemical analysis and fluorescence in situ hybridization (FISH) are the 2 most widely used methods to evaluate HER-2 status in breast cancer. Studies have shown that overexpression of the HER-2 protein is closely correlated with amplification of the HER-2 gene in tumors scored immunohistochemically as 3+, but not in tumors scored as 2+.[5-7] Studies also have indicated that HER-2 gene amplification determined by FISH seems to be a better predictor of response to trastuzumab-based therapy than HER-2 overexpression determined by immunohistochemical scores of 2+ to 3+.8,9 The accurate assessment of HER-2 gene amplification, therefore, has become critical in the management of these tumors.

Currently, there are 2 FISH-based assays for the assessment of HER-2 gene amplification. One is the US Food and Drug Administration-approved PathVysion HER-2 probe kit (Vysis, Downers Grove, IL). It uses probes for chromosome 17 centromere and HER-2 gene simultaneously, and HER-2 gene amplification is defined as a ratio of HER-2 gene copies per chromosome 17 copy equal to or greater than 2.0.[7,10] The other FISH assay is the Ventana INFORM HER-2 test (Ventana, Tucson, AZ). It uses the HER-2 probe alone, and defines HER-2 gene amplification as the absolute HER-2 gene copy number per tumor nucleus of greater than 4.0.[11,12] Some investigators[7,13] have found correction for chromosome 17 critical for determination of true gene amplification as opposed to increased HER-2 gene copy number due to polysomy 17, while others[14,15] believed it unnecessary.

We assessed concordance between 2 Food and Drug Administration-approved methods for evaluating HER-2 status, ie, the immunohistochemically based HercepTest (DAKO, Carpinteria, CA) and the FISH-based PathVysion assay. We also examined how the use of dual-color (D-FISH) vs single-color FISH (S-FISH) scoring might affect the assignment of tumors to amplified or nonamplified categories.




Priti Lal, MD,1 Paulo A. Salazar,1 Clifford A. Hudis, MD,2 Marc Ladanyi, MD,1 and Beiyun Chen, MD, PhD1

Departments of 1Pathology and 2Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY



Am J Clin Pathol 121(5):631-636, 2004. © 2004 American Society for Clinical Pathology