Androgen receptor determination in breast cancer: a comparison of the dextran-coated charcoal method and quantitative immunohistochemical analysis.
Androgen receptor (AR) expression is prognostic for breast cancer. Techniques to determine AR levels include the dextran-coated charcoal method (charc-AR), which measures AR levels in both normal and cancer cells; immunohistochemical analysis (1HC-AR) of whole sections (WS), which targets cancer cells but relies on subjective assay interpretation; and IHC of tissue microarray (TMA) samples, an approach that can be inaccurate when AR heterogeneity is present. This study compared charc-AR (n=151) with quantitative IHC analysis (n=138) of WS and TMA samples (1.7 mm cylinder samples; 2.3 mm). Charc-AR results correlated poorly with IHC-WS and IHC-TMA results due to the presence of AR-positive noncancer cells. IHC-WS revealed intertumor and intratumor AR heterogeneity. Consequently, the IHC-WS and IHC-TMA results were similar for tumors in which the percentage of AR-positive WS samples was >80% (31% of tumors), but differed in other tumors due to TMA false negatives (33%). Computer simulation was used to determine the optimal number and size of TMA samples for reliable results, and showed that five to eight 1.7 mm samples, or up to sixty-four 0.6 mm samples, were needed for reliable AR determination for most tumors. Thus, AR determination by charc-AR is inaccurate due to evaluation of both normal and cancer cells. IHC is more sensitive and specific than charc-AR in WS samples, but not when applied to single or a few TMA samples.
Department of Surgery, Stavanger University Hospital, Stavanger, The Netherlands.
Håvard
H
Søiland
Ivar
I
Skaland
Bianca
B
van Diermen
Emiel A M
EA
Janssen
Hartwig
H
Körner
Jan Erik
JE
Varhaug
Jon Arne
JA
Søreide
Jan P A
JP
Baak
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000378:metabolism; D002606:Charcoal; D003911:Dextrans; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011944:Receptors, Androgen / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D046888:Tissue Array Analysis
C410798:AR protein, human; D014408:Biomarkers, Tumor; D003911:Dextrans; D011944:Receptors, Androgen; D002606:Charcoal