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Basal biomarkers nestin and INPP4b identify intrinsic subtypes accurately in breast cancers that are weakly positive for oestrogen receptor.
- Source :
- Histopathology; Jan2017, Vol. 70 Issue 2, p185-194, 10p, 1 Color Photograph, 3 Charts, 3 Graphs
- Publication Year :
- 2017
-
Abstract
- Aims Recent evidence indicates that weakly positive immunohistochemical staining of oestrogen receptor ( ER) is not associated reliably with a luminal subtype, with the majority reclassified as basal-like by gene expression profile. In this study we assessed the capacity of recently identified immunohistochemical markers of basal-like subtype not dependent upon ER status - positive expression of nestin or loss of inositol polyphosphate-4-phosphatase ( INPP4b) - to discriminate intrinsic subtypes, focusing on clinically problematic cases with weak ER positivity. Methods and results Formalin-fixed paraffin-embedded blocks, enriched for large proportions of ER-negative and ER weakly positive breast cancers, were selected from two previous studies conducted in the period 2008-13 and used for (i) RNA extraction for 50-gene subtype predictor ( PAM50) intrinsic subtyping and (ii) tissue microarray construction for immunohistochemical assessment of nestin and INPP4b. Fifty-eight cases were weakly positive for ER (Allred 3-5), among which 28 (48%) were assigned as basal-like by PAM50 gene expression. In these 58 cases, the nestin/ INPP4b panel identified 23 basal-like cases with a positive predictive value of 87% [95% confidence interval (CI) 78-95%] and excluded luminal subtype with a negative predictive value of 95% (95% CI 88-100%). Weakly positive ER patients assigned as basal-like by nestin/INPP4b definition demonstrated a median survival time of 45.8 months, significantly lower than 65 months among other ER weakly positive cases ( P = 0.012). Conclusions Immunohistochemical assessment of nestin and INPP4b provides an accurate, accessible and inexpensive tool to identify basal-like breast cancer subtype in the clinically problematic setting of weak ER positivity. This panel identifies poor prognosis patients who might need strong considerations for non-endocrine-based therapies. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03090167
- Volume :
- 70
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Histopathology
- Publication Type :
- Academic Journal
- Accession number :
- 120173064
- Full Text :
- https://doi.org/10.1111/his.13038