Isoform specificity of progesterone receptor antibodies

Progesterone receptors (PR) are prognostic and predictive biomarkers in hormone‐dependent cancers. Two main PR isoforms have been described, PRB and PRA, that differ only in that PRB has 164 extra N‐terminal amino acids. It has been reported that several antibodies empirically exclusively recognize...

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Bibliographic Details
Published in:The journal of pathology. Clinical research 2017-10, Vol.3 (4), p.227-233
Main Authors: Fabris, Victoria, Abascal, María F, Giulianelli, Sebastián, May, María, Sequeira, Gonzalo R, Jacobsen, Britta, Lombès, Marc, Han, Julie, Tran, Luan, Molinolo, Alfredo, Lanari, Claudia
Format: Article
Language:English
Subjects:
Antibodies
Breast cancer
breast cancer models
Brief Definitive Report
Cloning
Immunoglobulins
Immunohistochemistry
Isoforms
Laboratory animals
Menopause
Paraffin
Progesterone
progesterone receptor isoforms
Progesterone receptors
specific antibodies
Studies
Tumors
Xenografts
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Summary:Progesterone receptors (PR) are prognostic and predictive biomarkers in hormone‐dependent cancers. Two main PR isoforms have been described, PRB and PRA, that differ only in that PRB has 164 extra N‐terminal amino acids. It has been reported that several antibodies empirically exclusively recognize PRA in formalin‐fixed paraffin‐embedded (FFPE) tissues. To confirm these findings, we used human breast cancer xenograft models, T47D‐YA and ‐YB cells expressing PRA or PRB, respectively, MDA‐MB‐231 cells modified to synthesize PRB, and MDA‐MB‐231/iPRAB cells which can bi‐inducibly express either PRA or PRB. Cells were injected into immunocompromised mice to generate tumours exclusively expressing PRA or PRB. PR isoform expression was verified using immunoblots. FFPE samples from the same tumours were studied by immunohistochemistry using H‐190, clone 636, clone 16, and Ab‐6 anti‐PR antibodies, the latter exclusively recognizing PRB. Except for Ab‐6, all antibodies displayed a similar staining pattern. Our results indicate that clones 16, 636, and the H‐190 antibody recognize both PR isoforms. They point to the need for more stringency in evaluating the true specificity of purported PRA‐specific antibodies as the PRA/PRB ratio may have prognostic and predictive value in breast cancer.
ISSN:2056-4538
2056-4538
DOI:10.1002/cjp2.83