Sources/Clones
Accurate (polyclonal), Biogenex (F39.4.1), Novocastra (2F12, polyclonal), Pharmingen (G122-25.3, G122-434, G122-77.14, AN1-15) and Sanbio/Monosan (F39.4.1).
Fixation/Preparation
The antibodies are immunoreactive in frozen sections, cell preparations and paraffin-embedded sections. HIER enhances the latter.
Background
The intracellular action of androgens is mediated by the androgen receptor, which is a key element of the androgen signal transduction cascade and a target of endocrine therapy for prostatic carcinoma. Qualitative and quantitative alterations of androgen receptor expression in prostatic carcinomas and their possible implications for tumor progression and treatment are therefore of diagnostic and research interest. Findings in prostatic tumor cell lines of rat and human origin suggest a reduction of androgen receptor protein expression accompanied by an increase in tumor aggressiveness. However, immunohistochemical analysis and binding assays have demonstrated the presence of androgen receptors in all histological types of prostatic carcinoma and in both therapy-responsive and therapy-unresponsive tumors.
Applications
Many of the immunohistochemical studies of androgen receptors have been related to prostatic carcinoma. The androgen receptor content of prostatic carcinoma has been inversely correlated to Gleason grade in stage D2 carcinomas, although it was unrelated to extent of disease and response to hormonal therapy at 3 months. Patients with 48% or more androgen receptor-positive cells had statistically significant better outcome in terms of both progression-free and cause-specific survival (Takeda et al, 1996). Another study suggested that pretreatment androgen receptor expression alone is not related to prognosis of hormonally treated prostate cancer; however, when combined with bcl-2 expression, it acts as an independent prognostic factor for clinical progression (Noordzij et al, 1997).
One explanation for the discrepancy in findings may relate to the mutations that occur in the androgen receptor, which account for the variable response to hormonal therapy. These mutations produce broadened ligand specificity so that transcriptional factor activity of the receptor can be stimulated not just by dihydrotestosterone but also by estradiol and other androgen metabolites. Such activation of mutant androgen receptors by estrogen and weak androgens could confer on prostate cancer cells an ability to survive testicular androgen ablation through the activation of the androgen receptor by adrenal androgens or exogenous estrogen. Thus, mutated androgen receptors that occur prior to therapy may characterize a more aggressive disease (Hakimi et al, 1996).
The variability of androgen receptor protein content per unit nuclear area has been shown to increase with increasing histological grade, suggesting that this variability might account for the variable response to endocrine therapy in high-grade tumors (Magi-Galluzzi et al, 1997). The extent of heterogeneity of androgen receptor expression may be a useful indicator of response to hormonal therapy (Kloker et al, 1994). Immunostaining for androgen receptor expression has been studied in other cell types including endometrium (Mertens et al, 1996), genital melanocytes (Tadokoro et al, 1997), meningiomas (Carroll et al, 1995) and urinary bladder carcinomas (Zhuang et al, 1997).
Comments
The receptor is intranuclear in location. A cut-off of 10% androgen receptor-positive cells has been suggested to maximize assay prognostic efficiency, with 48% positivity showing significant correlation with response, time to progression and survival, but not with grade or stage of prostatic cancer (Pertschuk et al, 1994). Clone G122-25 is immunoreactive in fixed, paraffin-embedded tissue sections and does not appear to crossreact with estrogen or progesterone receptors.
References
•Carroll RS, Zhang J, Dashmner K et al 1995. Androgen receptor expression in meningiomas. Journal of Neurosurgery 82: 453-460.
•Hakimi JM, Rondinelli RH, Schoenberg MP, Barrack ER 1996. Androgen-receptor gene structure and function in prostate cancer. World Journal of Urology 14: 329-337.
•Kloker H, Culig Z, Hobisch A et al 1994. Androgen receptor alterations in prostatic carcinoma. Prostate 25: 266-273.
•Magi-Galluzzi C, Xu X, Hlatky L et al 1997. Heterogeneity of androgen receptor content in advanced prostate cancer. Modern Pathology 10:839-845.
•Mertens HJ, Heineman MJ, Koudstaal J et al 1996. Androgen receptor content in human endometrium.
•European Journal of Obstetrics, Gynecology and Reproductive Biology 70: 11-13.
•Noordzij MA, Bogdanowicz JF, Van Krimpen C et al 1997. The prognostic value of pretreatment expression of androgen receptor and bcl-2 in hormonally treated prostate cancer patients.
• Journal of Urology 158: 1880-1884.
•Pertschuk LP, Macchia RJ, Feldman JG et al 1994. Immunocytochemical assay for androgen receptors in prostate cancer: a prospective study of 63 cases with long-term follow-up.
•Annals of Surgical Oncology 1: 495-503.
•Tadokoro T, Itami S, Hosokawa K, et al 1997. Human genital melanocytes as androgen target cells.
•Journal of Investigative Dermatology 109:513-517.
•Takeda H, Akakura K, Masai M et al 1996. Androgen receptor content of prostate carcinoma cells estimated by immunohistochemistry is related to prognosis of patients with stage D2 prostate carcinoma. Cancer 77: 934-940.
•Zhuang YH, Blauer M, Tammela T, Tuohimaa P 1997. Immunodetection of androgen receptor in human urinary bladder cancer. Histopathology 30: 556-562.
Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
Accurate (polyclonal), Biogenex (F39.4.1), Novocastra (2F12, polyclonal), Pharmingen (G122-25.3, G122-434, G122-77.14, AN1-15) and Sanbio/Monosan (F39.4.1).
Fixation/Preparation
The antibodies are immunoreactive in frozen sections, cell preparations and paraffin-embedded sections. HIER enhances the latter.
Background
The intracellular action of androgens is mediated by the androgen receptor, which is a key element of the androgen signal transduction cascade and a target of endocrine therapy for prostatic carcinoma. Qualitative and quantitative alterations of androgen receptor expression in prostatic carcinomas and their possible implications for tumor progression and treatment are therefore of diagnostic and research interest. Findings in prostatic tumor cell lines of rat and human origin suggest a reduction of androgen receptor protein expression accompanied by an increase in tumor aggressiveness. However, immunohistochemical analysis and binding assays have demonstrated the presence of androgen receptors in all histological types of prostatic carcinoma and in both therapy-responsive and therapy-unresponsive tumors.
Applications
Many of the immunohistochemical studies of androgen receptors have been related to prostatic carcinoma. The androgen receptor content of prostatic carcinoma has been inversely correlated to Gleason grade in stage D2 carcinomas, although it was unrelated to extent of disease and response to hormonal therapy at 3 months. Patients with 48% or more androgen receptor-positive cells had statistically significant better outcome in terms of both progression-free and cause-specific survival (Takeda et al, 1996). Another study suggested that pretreatment androgen receptor expression alone is not related to prognosis of hormonally treated prostate cancer; however, when combined with bcl-2 expression, it acts as an independent prognostic factor for clinical progression (Noordzij et al, 1997).
One explanation for the discrepancy in findings may relate to the mutations that occur in the androgen receptor, which account for the variable response to hormonal therapy. These mutations produce broadened ligand specificity so that transcriptional factor activity of the receptor can be stimulated not just by dihydrotestosterone but also by estradiol and other androgen metabolites. Such activation of mutant androgen receptors by estrogen and weak androgens could confer on prostate cancer cells an ability to survive testicular androgen ablation through the activation of the androgen receptor by adrenal androgens or exogenous estrogen. Thus, mutated androgen receptors that occur prior to therapy may characterize a more aggressive disease (Hakimi et al, 1996).
The variability of androgen receptor protein content per unit nuclear area has been shown to increase with increasing histological grade, suggesting that this variability might account for the variable response to endocrine therapy in high-grade tumors (Magi-Galluzzi et al, 1997). The extent of heterogeneity of androgen receptor expression may be a useful indicator of response to hormonal therapy (Kloker et al, 1994). Immunostaining for androgen receptor expression has been studied in other cell types including endometrium (Mertens et al, 1996), genital melanocytes (Tadokoro et al, 1997), meningiomas (Carroll et al, 1995) and urinary bladder carcinomas (Zhuang et al, 1997).
Comments
The receptor is intranuclear in location. A cut-off of 10% androgen receptor-positive cells has been suggested to maximize assay prognostic efficiency, with 48% positivity showing significant correlation with response, time to progression and survival, but not with grade or stage of prostatic cancer (Pertschuk et al, 1994). Clone G122-25 is immunoreactive in fixed, paraffin-embedded tissue sections and does not appear to crossreact with estrogen or progesterone receptors.
References
•Carroll RS, Zhang J, Dashmner K et al 1995. Androgen receptor expression in meningiomas. Journal of Neurosurgery 82: 453-460.
•Hakimi JM, Rondinelli RH, Schoenberg MP, Barrack ER 1996. Androgen-receptor gene structure and function in prostate cancer. World Journal of Urology 14: 329-337.
•Kloker H, Culig Z, Hobisch A et al 1994. Androgen receptor alterations in prostatic carcinoma. Prostate 25: 266-273.
•Magi-Galluzzi C, Xu X, Hlatky L et al 1997. Heterogeneity of androgen receptor content in advanced prostate cancer. Modern Pathology 10:839-845.
•Mertens HJ, Heineman MJ, Koudstaal J et al 1996. Androgen receptor content in human endometrium.
•European Journal of Obstetrics, Gynecology and Reproductive Biology 70: 11-13.
•Noordzij MA, Bogdanowicz JF, Van Krimpen C et al 1997. The prognostic value of pretreatment expression of androgen receptor and bcl-2 in hormonally treated prostate cancer patients.
• Journal of Urology 158: 1880-1884.
•Pertschuk LP, Macchia RJ, Feldman JG et al 1994. Immunocytochemical assay for androgen receptors in prostate cancer: a prospective study of 63 cases with long-term follow-up.
•Annals of Surgical Oncology 1: 495-503.
•Tadokoro T, Itami S, Hosokawa K, et al 1997. Human genital melanocytes as androgen target cells.
•Journal of Investigative Dermatology 109:513-517.
•Takeda H, Akakura K, Masai M et al 1996. Androgen receptor content of prostate carcinoma cells estimated by immunohistochemistry is related to prognosis of patients with stage D2 prostate carcinoma. Cancer 77: 934-940.
•Zhuang YH, Blauer M, Tammela T, Tuohimaa P 1997. Immunodetection of androgen receptor in human urinary bladder cancer. Histopathology 30: 556-562.
Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
