Positive HER-2 protein expression in circulating prostate cells and micro-metastasis, resistant to androgen blockage but not diethylstilbestrol
Introduction : HER-2 expression in prostate cancer is associated with a worse prognosis and is suggested to play a role in androgen resistance. We present a study of HER-2 expression in circulating tumor cells and micrometastasis in bone marrow and the effect of androgen blockage or DES in the prese...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2011-01-01
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| Series: | Indian Journal of Urology |
| Subjects: | |
| Online Access: | http://www.indianjurol.com/article.asp?issn=0970-1591;year=2011;volume=27;issue=2;spage=200;epage=207;aulast=Murray |
| _version_ | 1819156389457559552 |
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| author | Nigel P Murray Leonardo V Badinez Ricardo R Dueñas Nelson Orellana Pablo Tapia |
| author_facet | Nigel P Murray Leonardo V Badinez Ricardo R Dueñas Nelson Orellana Pablo Tapia |
| author_sort | Nigel P Murray |
| collection | DOAJ |
| description | Introduction : HER-2 expression in prostate cancer is associated with a worse prognosis and is suggested to play a role in androgen resistance. We present a study of HER-2 expression in circulating tumor cells and micrometastasis in bone marrow and the effect of androgen blockage or DES in the presence of HER-2 expressing cells.
Patients and Methods : A multicenter study of men with prostate cancer, treated with surgery, radiotherapy, or observation, and with or without hormone therapy. Mononuclear cells were separated from blood and bone marrow aspirate by differential centrifugation, touch preps were made from bone marrow biopsy samples. Prostate cells were detected using anti-PSA monoclonal antibody and standard immunocytochemistry. Positive samples were processed using Herceptest® to determine HER-2 expression. After 1 year, patients were re-evaluated and the findings of HER-2 expression and PSA change compared with treatment.
Results : Total 199 men participated, and 97 had a second evaluation 1 year later, frequency of HER-2 expression in circulating tumor cells and micrometastasis was 18% and 21%, respectively. There was no significant difference in HER-2 expression in the pretreatment group, after radical surgery or radiotherapy or with biochemical failure. Men with androgen blockade had a significantly higher expression of HER-2 (58%) (P =0.001). Of the 97 men with a second evaluation, 56 were in the observation arm, 27 androgen blockade, and 14 DES. Use of androgen blockade or DES significantly reduced serum PSA levels in comparison with observation (P =0.001). However, there was a significant increase in HER-2 expression in patients with androgen blockade (P =0.05) en comparison with observation or DES treatment. No patient with observation or DES became HER-2 positive, en comparison 4/22 patients initially HER-2 negative became HER-2 positive with androgen blockade.
Conclusions : The results suggest that HER-2 positive cells are resistant to androgen blockade. In an environment lacking androgens, HER-2 positive cells are selected and survive, while HER-2 negative cells are eliminated thus decreasing the serum PSA. The population of HER-2 positive cells proliferate producing androgen-independent disease. DES does not increase HER-2 expression possibly by stimulating beta-estrogen receptors and blocking HER-2 androgen receptor activation. |
| first_indexed | 2024-12-22T15:52:06Z |
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| id | doaj.art-6725d6535a724624813945ae47c83dcf |
| institution | Directory Open Access Journal |
| issn | 0970-1591 1998-3824 |
| language | English |
| last_indexed | 2024-12-22T15:52:06Z |
| publishDate | 2011-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Indian Journal of Urology |
| spelling | doaj.art-6725d6535a724624813945ae47c83dcf2022-12-21T18:20:52ZengWolters Kluwer Medknow PublicationsIndian Journal of Urology0970-15911998-38242011-01-0127220020710.4103/0970-1591.82838Positive HER-2 protein expression in circulating prostate cells and micro-metastasis, resistant to androgen blockage but not diethylstilbestrolNigel P MurrayLeonardo V BadinezRicardo R DueñasNelson OrellanaPablo TapiaIntroduction : HER-2 expression in prostate cancer is associated with a worse prognosis and is suggested to play a role in androgen resistance. We present a study of HER-2 expression in circulating tumor cells and micrometastasis in bone marrow and the effect of androgen blockage or DES in the presence of HER-2 expressing cells. Patients and Methods : A multicenter study of men with prostate cancer, treated with surgery, radiotherapy, or observation, and with or without hormone therapy. Mononuclear cells were separated from blood and bone marrow aspirate by differential centrifugation, touch preps were made from bone marrow biopsy samples. Prostate cells were detected using anti-PSA monoclonal antibody and standard immunocytochemistry. Positive samples were processed using Herceptest® to determine HER-2 expression. After 1 year, patients were re-evaluated and the findings of HER-2 expression and PSA change compared with treatment. Results : Total 199 men participated, and 97 had a second evaluation 1 year later, frequency of HER-2 expression in circulating tumor cells and micrometastasis was 18% and 21%, respectively. There was no significant difference in HER-2 expression in the pretreatment group, after radical surgery or radiotherapy or with biochemical failure. Men with androgen blockade had a significantly higher expression of HER-2 (58%) (P =0.001). Of the 97 men with a second evaluation, 56 were in the observation arm, 27 androgen blockade, and 14 DES. Use of androgen blockade or DES significantly reduced serum PSA levels in comparison with observation (P =0.001). However, there was a significant increase in HER-2 expression in patients with androgen blockade (P =0.05) en comparison with observation or DES treatment. No patient with observation or DES became HER-2 positive, en comparison 4/22 patients initially HER-2 negative became HER-2 positive with androgen blockade. Conclusions : The results suggest that HER-2 positive cells are resistant to androgen blockade. In an environment lacking androgens, HER-2 positive cells are selected and survive, while HER-2 negative cells are eliminated thus decreasing the serum PSA. The population of HER-2 positive cells proliferate producing androgen-independent disease. DES does not increase HER-2 expression possibly by stimulating beta-estrogen receptors and blocking HER-2 androgen receptor activation.http://www.indianjurol.com/article.asp?issn=0970-1591;year=2011;volume=27;issue=2;spage=200;epage=207;aulast=MurrayAndrogen blockadecirculating tumor cellsDESHER-2micrometastasisprostate cancer |
| spellingShingle | Nigel P Murray Leonardo V Badinez Ricardo R Dueñas Nelson Orellana Pablo Tapia Positive HER-2 protein expression in circulating prostate cells and micro-metastasis, resistant to androgen blockage but not diethylstilbestrol Indian Journal of Urology Androgen blockade circulating tumor cells DES HER-2 micrometastasis prostate cancer |
| title | Positive HER-2 protein expression in circulating prostate cells and micro-metastasis, resistant to androgen blockage but not diethylstilbestrol |
| title_full | Positive HER-2 protein expression in circulating prostate cells and micro-metastasis, resistant to androgen blockage but not diethylstilbestrol |
| title_fullStr | Positive HER-2 protein expression in circulating prostate cells and micro-metastasis, resistant to androgen blockage but not diethylstilbestrol |
| title_full_unstemmed | Positive HER-2 protein expression in circulating prostate cells and micro-metastasis, resistant to androgen blockage but not diethylstilbestrol |
| title_short | Positive HER-2 protein expression in circulating prostate cells and micro-metastasis, resistant to androgen blockage but not diethylstilbestrol |
| title_sort | positive her 2 protein expression in circulating prostate cells and micro metastasis resistant to androgen blockage but not diethylstilbestrol |
| topic | Androgen blockade circulating tumor cells DES HER-2 micrometastasis prostate cancer |
| url | http://www.indianjurol.com/article.asp?issn=0970-1591;year=2011;volume=27;issue=2;spage=200;epage=207;aulast=Murray |
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