title: A survey of immunohistochemical biomarkers for basal-like breast cancer against a gene expression profile gold standard.
abstract: Gene expression profiling of breast cancer delineates a particularly aggressive subtype referred to as 'basal-like', which comprises ∼15% of all breast cancers, afflicts younger women and is refractory to endocrine and anti-HER2 therapies. Immunohistochemical surrogate definitions for basal-like breast cancer, such as the clinical ER/PR/HER2 triple-negative phenotype and models incorporating positive expression for CK5 (CK5/6) and/or EGFR are heavily cited. However, many additional biomarkers for basal-like breast cancer have been described in the literature. A parallel comparison of 46 proposed immunohistochemical biomarkers of basal-like breast cancer was performed against a gene expression profile gold standard on a tissue microarray containing 42 basal-like and 80 non-basal-like breast cancer cases. Ki67 and PPH3 were the most sensitive biomarkers (both 92%) positively expressed in the basal-like subtype, whereas CK14, IMP3 and NGFR were the most specific (100%). Among biomarkers surveyed, loss of INPP4B (a negative regulator of phosphatidylinositol signaling) was 61% sensitive and 99% specific with the highest odds ratio (OR) at 108, indicating the strongest association with basal-like breast cancer. Expression of nestin, a common marker of neural progenitor cells that is also associated with the triple-negative/basal-like phenotype and poor breast cancer prognosis, possessed the second highest OR at 29 among the 46 biomarkers surveyed, as well as 54% sensitivity and 96% specificity. As a positively expressed biomarker, nestin possesses technical advantages over INPP4B that make it a more ideal biomarker for identification of basal-like breast cancer. The comprehensive immunohistochemical biomarker survey presented in this study is a necessary step for determining an optimized surrogate immunopanel that best defines basal-like breast cancer in a practical and clinically accessible way.
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada [2] Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Won
authors.forename: Dongxia
authors.initials: D
authors.lastname: Gao
authors.forename: Christine
authors.initials: C
authors.lastname: Chow
authors.forename: Jinjin
authors.initials: J
authors.lastname: Cheng
authors.forename: Sherman Y H
authors.initials: SY
authors.lastname: Lau
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellis
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: Philip S
authors.initials: PS
authors.lastname: Bernard
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000145:classification / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000592:standards*; D005820:Genetic Testing / Q000592:standards*; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards*; D064231:Nestin / Q000032:analysis; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D046888:Tissue Array Analysis / Q000592:standards
chemical_list: D014408:Biomarkers, Tumor; C577484:NES protein, human; D064231:Nestin; D010744:Phosphoric Monoester Hydrolases; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase