Comparison of quantitative immunofluorescence with conventional methods for HER2/neu testing with respect to response to trastuzumab therapy in metastatic breast cancer.

Author(s): Giltnane JM, Molinaro A, Cheng H, Robinson A, Turbin D, Gelmon K, Huntsman D, Rimm DL

Publication: Arch Pathol Lab Med, 2008, Vol. 132, Page 1635-47

PubMed ID: 18834223 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   The purpose of this study was to compare HER2 status by FISH, standard IHC and IHC using AQUA for whole sections and HER-2 status using AQUA for TMAs from 152 cases of breast cancer treated with trastuzumab therapy. The cohort was chosen based on diagnostic HER2 score of the whole section. Two 0.6 mm cores for each case were included in each array. AQUA scoring was only completed for TMAs.

   Summary of Findings:

   Of 83 cases with an IHC HER2 score of 2+ or 3+ for the whole section, 33.7% had a score of 0 or 1+ when TMAs were analyzed manually . Similarly, although FISH scores of whole sections were modestly correlated with those for the TMA (R=0.450), only 32 of the 52 cases (61.6%) with a ratio of HER2 to chromosome enumeration probe 17 (CEP17) greater than 2 for the whole section had a ratio greater than 2 when the TMA was analyzed. TMA AQUA scores were associated with both standard IHC scores and gene amplification determined by FISH. The standard IHC scores for TMAs were more closely related to the TMA AQUA scores (p<0.001) than the standard IHC score for the whole section (p=0.003). TMA AQUA scores were also associated with FISH results observed for whole sections and TMA, but the TMA scores were lower than the whole section scores. There was no association between the four categories of cancer response to trastuzumab and whole section FISH (p=0.96), TMA FISH (p=0.55), whole section IHC (p=0.75) or TMA IHC (p=0.06) scores, but the association of the 4 categories of trastuzumab response with the TMA IHC AQUA score was significant (p=0.01). An IHC TMA conventional score of 3+, or an IHC TMA AQUA score of more than 20 was significantly associated (p=0.03 and p=0.02, respectively) with a complete or partial response to trastuzumab therapy.

   Biospecimens

   • Tissue - Breast

   Preservative Types

   • Formalin

   Diagnoses:

   • Neoplastic - Carcinoma

   Platform:

   Analyte	Technology Platform
   Protein	Immunohistochemistry
   Protein	Tissue microarray
   DNA	FISH
   DNA	Tissue microarray

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Biospecimen Aliquots and Components	Type of slide	Whole section Tissue microarray
   Immunohistochemistry Specific	Targeted peptide/protein	HER2
   FISH Specific	Targeted nucleic acid	HER2
   Preaquisition	Prognostic factor	Progressive disease Stable disease Partial response Complete response
   Immunohistochemistry Specific	Data handling	AQUA scoring Manual scoring

   View more