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JMD 2004, Vol. 6, No. 1
Copyright © 2004 American Society for Investigative Pathology & Association for Molecular Pathology

Chromogenic In Situ Hybridization for 6ß4 Integrin in Breast Cancer

Correlation with Protein Expression

From the Department of Pathology, M.D. Anderson Cancer Center, Houston, Texas

The 6ß4 integrin is the receptor for the basement membrane protein laminin-5. Recent studies suggest that 6ß4 integrin expression in invasive breast carcinomas may be a poor prognostic factor. Because we have not had reliable results with commercially available antibodies for the immunohistochemical detection of 6ß4 integrin in archival paraffin-embedded tissues, we designed a probe to detect ß4 integrin subunit mRNA in paraffin sections. In situ hybridization for ß4 mRNA was performed on paraffin-embedded tissue sections of 25 invasive breast carcinomas using a hyperbiotinylated oligonucleotide DNA probe. Immunohistochemical staining was performed on corrresponding frozen tumor sections using two commercially available antibodies to the ß4 integrin subunit. All cases positive for ß4 protein by one or both antibodies were also positive for ß4 mRNA by in situ hybridization, but three cases with ß4 mRNA expression were negative by immunohistochemistry with both antibodies. These findings suggest that in situ hybridization appears to be a sensitive method for detecting ß4 integrin mRNA, but it appears to identify some cases that either lack ß4 protein or express variants not recognized with commercial antibodies directed to particular extracellular or cytoplasmic domains.

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