| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
|
|
|
|
|||||||||||||
|
|
|||||||||||||||
1 Westmead Institute for Cancer Research, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia
2 Department of Cell Biology, University of Tampere, 33014 University of Tampere, 33014, Finland
3 Department of Anatomy, Medical School, University of Tampere
Dr Mote patricia_mote{at}mail.wmi.usyd.edu.au Aim—The measurement of progesterone receptors (PR) is recommended as part of the clinical management of breast and endometrial cancers, and immunohistochemistry on formalin fixed tissue is now the method of choice. PR is expressed as two isoforms, PRA and PRB, and although both these proteins are expressed in hormone dependent cancers, there is evidence that a large proportion of tumours express a predominance of one isoform. Therefore, it is essential to document the individual detection of PRA and PRB by the presently available anti-PR antibodies. The aim of this study is to investigate the detection of PR isoforms A and B in formalin fixed, paraffin wax embedded cell lines and tissue sections by immunohistochemistry, using a panel of commercial and in house antibodies to human PR.
Methods—PR negative cell lines stably transfected to express only PRA (MCF-7Mll/PRA) or PRB (MDA-MB-231/PRB), and tissue sections of human breast carcinoma and normal endometrium were stained using an immunoperoxidase method. A panel of primary PR specific antibodies was evaluated for ability to detect both PRA and PRB proteins, and for intensity and distribution of positive staining under optimal conditions.
Results—Of the 11 antibodies assessed, only four recognised PRA and PRB similarly. Six recognised PRA proteins but were unable to detect PRB expression in the cell lines expressing only PRA or PRB. In tissues expressing high amounts of PRA and PRB, all antibodies tested demonstrated positive PR staining. However, in tissues expressing a predominance of PRB, differential staining patterns were observed, with variations in staining intensity and in the proportion of cells positive for PR.
Conclusions—Most PR specific antibodies tested failed to detect PRB in formalin fixed tissue by immunohistochemical techniques, despite their ability to do so by immunoblot analysis. These observations suggest that there are conformational differences between PRA and PRB that mask epitopes on the PRB protein recognised by most anti-PR antibodies. The selection of antibodies that recognise both PRB and PRA in formalin fixed tissue is essential for the accurate evaluation of PR positivity in clinical specimens.
Key Words: progesterone receptor isoforms • progesterone receptor antibodies • immunohistochemistry
This article has been cited by other articles:
|
|
 |
|
  O. Bukulmez, D. B. Hardy, B. R. Carr, R. A. Word, and C. R. Mendelson Inflammatory Status Influences Aromatase and Steroid Receptor Expression in Endometriosis Endocrinology, March 1, 2008; 149(3): 1190 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Britt, A. Ashworth, and M. Smalley Pregnancy and the risk of breast cancer Endocr. Relat. Cancer, December 1, 2007; 14(4): 907 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kariagina, M. D. Aupperlee, and S. Z. Haslam Progesterone Receptor Isoforms and Proliferation in the Rat Mammary Gland during Development Endocrinology, June 1, 2007; 148(6): 2723 - 2736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Aupperlee and S. Z. Haslam Differential Hormonal Regulation and Function of Progesterone Receptor Isoforms in Normal Adult Mouse Mammary Gland Endocrinology, May 1, 2007; 148(5): 2290 - 2300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Arnett-Mansfield, J. D. Graham, A. R. Hanson, P. A. Mote, A. Gompel, L. L. Scurr, N. Gava, A. de Fazio, and C. L. Clarke Focal Subnuclear Distribution of Progesterone Receptor Is Ligand Dependent and Associated with Transcriptional Activity Mol. Endocrinol., January 1, 2007; 21(1): 14 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Mote, R. L. Arnett-Mansfield, N. Gava, A. deFazio, B. Mulac-Jericevic, O. M. Conneely, and C. L. Clarke Overlapping and Distinct Expression of Progesterone Receptors A and B in Mouse Uterus and Mammary Gland during the Estrous Cycle Endocrinology, December 1, 2006; 147(12): 5503 - 5512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pilka, I. Oborna, V. Lichnovsky, P. Havelka, H. Fingerova, P. Eriksson, S. Hansson, and B. Casslen Endometrial expression of the estrogen-sensitive genes MMP-26 and TIMP-4 is altered by a substitution protocol without down-regulation in IVF patients Hum. Reprod., December 1, 2006; 21(12): 3146 - 3156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-L. Asselin-Labat, M. Shackleton, J. Stingl, F. Vaillant, N. C. Forrest, C. J. Eaves, J. E. Visvader, and G. J. Lindeman Steroid hormone receptor status of mouse mammary stem cells. J Natl Cancer Inst, July 19, 2006; 98(14): 1011 - 1014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Taylor, P. C. McParland, D. J. Taylor, and S. C. Bell The Progesterone Receptor in Human Term Amniochorion and Placenta Is Isoform C Endocrinology, February 1, 2006; 147(2): 687 - 693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Aupperlee, K. T. Smith, A. Kariagina, and S. Z. Haslam Progesterone Receptor Isoforms A and B: Temporal and Spatial Differences in Expression during Murine Mammary Gland Development Endocrinology, August 1, 2005; 146(8): 3577 - 3588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Cheng, Y. Li, Y. Omoto, Y. Wang, T. Berg, M. Nord, P. Vihko, M. Warner, Y.-S. Piao, and J.-A. Gustafsson Differential Regulation of Estrogen Receptor (ER){alpha} and ER{beta} in Primate Mammary Gland J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 435 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bagheri-Yarmand, A. H. Talukder, R.-A. Wang, R. K. Vadlamudi, and R. Kumar Metastasis-associated protein 1 deregulation causes inappropriate mammary gland development and tumorigenesis Development, July 15, 2004; 131(14): 3469 - 3479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Gava, C. L. Clarke, K. Byth, R. L. Arnett-Mansfield, and A. deFazio Expression of Progesterone Receptors A and B in the Mouse Ovary during the Estrous Cycle Endocrinology, July 1, 2004; 145(7): 3487 - 3494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Hopp, H. L. Weiss, S. G. Hilsenbeck, Y. Cui, D. C. Allred, K. B. Horwitz, and S. A. W. Fuqua Breast Cancer Patients with Progesterone Receptor PR-A-Rich Tumors Have Poorer Disease-Free Survival Rates Clin. Cancer Res., April 15, 2004; 10(8): 2751 - 2760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Arnett-Mansfield, A. deFazio, P. A. Mote, and C. L. Clarke Subnuclear Distribution of Progesterone Receptors A and B in Normal and Malignant Endometrium J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1429 - 1442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Mandelin, H. Lassus, M. Seppala, A. Leminen, J.-A. Gustafsson, G. Cheng, R. Butzow, and R. Koistinen Glycodelin in Ovarian Serous Carcinoma: Association with Differentiation and Survival Cancer Res., October 1, 2003; 63(19): 6258 - 6264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-C. Chou, N. Uehara, J. R. Lowry, and G. Shyamala Mammary epithelial cells of PR-A transgenic mice exhibit distinct alterations in gene expression and growth potential associated with transformation Carcinogenesis, March 1, 2003; 24(3): 403 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Saji, Y. Omoto, C. Shimizu, M. Warner, Y. Hayashi, S.-i. Horiguchi, T. Watanabe, S.-i. Hayashi, J.-A. Gustafsson, and M. Toi Expression of Estrogen Receptor (ER) {beta}cx Protein in ER{alpha}-positive Breast Cancer: Specific Correlation with Progesterone Receptor Cancer Res., September 1, 2002; 62(17): 4849 - 4853. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Richer, B. M. Jacobsen, N. G. Manning, M. G. Abel, D. M. Wolf, and K. B. Horwitz Differential Gene Regulation by the Two Progesterone Receptor Isoforms in Human Breast Cancer Cells J. Biol. Chem., February 8, 2002; 277(7): 5209 - 5218. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
| Journal of Clinical Pathology | Molecular Pathology |
