Her-2-neu expression and progression toward androgen independence in human prostate cancer

Sabina Signoretti, Rodolfo Montironi, Judith Manola, Annalisa Altimari, Carmen Tam, Glenn Bubley, Steven Balk, George Thomas, Irving Kaplan, Lynn Hlatky, Philip Hahnfeldt, Philip Kantoff, Massimo Loda

Research output: Contribution to journalArticle

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Abstract

Background: Human prostate cancers are initially androgen dependent but ultimately become androgen independent. Overexpression of the Her-2-neu receptor tyrosine kinase has been associated with the progression to androgen independence in prostate cancer cells. We examined the expression of Her-2-neu in normal and cancerous prostate tissues to assess its role in the progression to androgen independence. Methods: Prostate cancer tissue sections were obtained from 67 patients treated by surgery alone (UNT tumors), 34 patients treated with total androgen ablation therapy before surgery (TAA tumors), and 18 patients in whom total androgen ablation therapy failed and who developed bone metastases (androgen-independent [AI] disease). The sections were immunostained for Her-2-neu, androgen receptor (AR), prostate-specific antigen (PSA), and Ki-67 (a marker of cell proliferation) protein expression. Messenger RNA (mRNA) levels and gene amplification of Her-2-neu were examined by RNA in situ hybridization and fluorescent in situ hybridization (FISH), respectively, in a subset of 27 tumors (nine UNT, 11 TAA, and seven AI). All statistical tests were two-sided. Results: Her-2-neu protein expression was statistically significantly higher in TAA tumors than in UNT tumors with the use of two different scoring methods (P = .008 and P = .002). The proportion of Her-2-neu-positive tumors increased from the UNT group (17 of 67) to the TAA group (20 of 34) to the AI group (14 of 18) (P

Original languageEnglish (US)
Pages (from-to)1918-1925
Number of pages8
JournalJournal of the National Cancer Institute
Volume92
Issue number23
StatePublished - Dec 6 2000
Externally publishedYes

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Androgens
Prostatic Neoplasms
ErbB-2 Receptor
Neoplasms
Gene Amplification
Androgen Receptors
Prostate-Specific Antigen
Fluorescence In Situ Hybridization
Protein-Tyrosine Kinases
In Situ Hybridization
Prostate
Proteins
Research Design
Cell Proliferation
RNA
Neoplasm Metastasis
Bone and Bones
Messenger RNA
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Signoretti, S., Montironi, R., Manola, J., Altimari, A., Tam, C., Bubley, G., ... Loda, M. (2000). Her-2-neu expression and progression toward androgen independence in human prostate cancer. Journal of the National Cancer Institute, 92(23), 1918-1925.

Her-2-neu expression and progression toward androgen independence in human prostate cancer. / Signoretti, Sabina; Montironi, Rodolfo; Manola, Judith; Altimari, Annalisa; Tam, Carmen; Bubley, Glenn; Balk, Steven; Thomas, George; Kaplan, Irving; Hlatky, Lynn; Hahnfeldt, Philip; Kantoff, Philip; Loda, Massimo.

In: Journal of the National Cancer Institute, Vol. 92, No. 23, 06.12.2000, p. 1918-1925.

Research output: Contribution to journalArticle

Signoretti, S, Montironi, R, Manola, J, Altimari, A, Tam, C, Bubley, G, Balk, S, Thomas, G, Kaplan, I, Hlatky, L, Hahnfeldt, P, Kantoff, P & Loda, M 2000, 'Her-2-neu expression and progression toward androgen independence in human prostate cancer', Journal of the National Cancer Institute, vol. 92, no. 23, pp. 1918-1925.
Signoretti S, Montironi R, Manola J, Altimari A, Tam C, Bubley G et al. Her-2-neu expression and progression toward androgen independence in human prostate cancer. Journal of the National Cancer Institute. 2000 Dec 6;92(23):1918-1925.
Signoretti, Sabina ; Montironi, Rodolfo ; Manola, Judith ; Altimari, Annalisa ; Tam, Carmen ; Bubley, Glenn ; Balk, Steven ; Thomas, George ; Kaplan, Irving ; Hlatky, Lynn ; Hahnfeldt, Philip ; Kantoff, Philip ; Loda, Massimo. / Her-2-neu expression and progression toward androgen independence in human prostate cancer. In: Journal of the National Cancer Institute. 2000 ; Vol. 92, No. 23. pp. 1918-1925.
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abstract = "Background: Human prostate cancers are initially androgen dependent but ultimately become androgen independent. Overexpression of the Her-2-neu receptor tyrosine kinase has been associated with the progression to androgen independence in prostate cancer cells. We examined the expression of Her-2-neu in normal and cancerous prostate tissues to assess its role in the progression to androgen independence. Methods: Prostate cancer tissue sections were obtained from 67 patients treated by surgery alone (UNT tumors), 34 patients treated with total androgen ablation therapy before surgery (TAA tumors), and 18 patients in whom total androgen ablation therapy failed and who developed bone metastases (androgen-independent [AI] disease). The sections were immunostained for Her-2-neu, androgen receptor (AR), prostate-specific antigen (PSA), and Ki-67 (a marker of cell proliferation) protein expression. Messenger RNA (mRNA) levels and gene amplification of Her-2-neu were examined by RNA in situ hybridization and fluorescent in situ hybridization (FISH), respectively, in a subset of 27 tumors (nine UNT, 11 TAA, and seven AI). All statistical tests were two-sided. Results: Her-2-neu protein expression was statistically significantly higher in TAA tumors than in UNT tumors with the use of two different scoring methods (P = .008 and P = .002). The proportion of Her-2-neu-positive tumors increased from the UNT group (17 of 67) to the TAA group (20 of 34) to the AI group (14 of 18) (P",
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AU - Signoretti, Sabina

AU - Montironi, Rodolfo

AU - Manola, Judith

AU - Altimari, Annalisa

AU - Tam, Carmen

AU - Bubley, Glenn

AU - Balk, Steven

AU - Thomas, George

AU - Kaplan, Irving

AU - Hlatky, Lynn

AU - Hahnfeldt, Philip

AU - Kantoff, Philip

AU - Loda, Massimo

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N2 - Background: Human prostate cancers are initially androgen dependent but ultimately become androgen independent. Overexpression of the Her-2-neu receptor tyrosine kinase has been associated with the progression to androgen independence in prostate cancer cells. We examined the expression of Her-2-neu in normal and cancerous prostate tissues to assess its role in the progression to androgen independence. Methods: Prostate cancer tissue sections were obtained from 67 patients treated by surgery alone (UNT tumors), 34 patients treated with total androgen ablation therapy before surgery (TAA tumors), and 18 patients in whom total androgen ablation therapy failed and who developed bone metastases (androgen-independent [AI] disease). The sections were immunostained for Her-2-neu, androgen receptor (AR), prostate-specific antigen (PSA), and Ki-67 (a marker of cell proliferation) protein expression. Messenger RNA (mRNA) levels and gene amplification of Her-2-neu were examined by RNA in situ hybridization and fluorescent in situ hybridization (FISH), respectively, in a subset of 27 tumors (nine UNT, 11 TAA, and seven AI). All statistical tests were two-sided. Results: Her-2-neu protein expression was statistically significantly higher in TAA tumors than in UNT tumors with the use of two different scoring methods (P = .008 and P = .002). The proportion of Her-2-neu-positive tumors increased from the UNT group (17 of 67) to the TAA group (20 of 34) to the AI group (14 of 18) (P

AB - Background: Human prostate cancers are initially androgen dependent but ultimately become androgen independent. Overexpression of the Her-2-neu receptor tyrosine kinase has been associated with the progression to androgen independence in prostate cancer cells. We examined the expression of Her-2-neu in normal and cancerous prostate tissues to assess its role in the progression to androgen independence. Methods: Prostate cancer tissue sections were obtained from 67 patients treated by surgery alone (UNT tumors), 34 patients treated with total androgen ablation therapy before surgery (TAA tumors), and 18 patients in whom total androgen ablation therapy failed and who developed bone metastases (androgen-independent [AI] disease). The sections were immunostained for Her-2-neu, androgen receptor (AR), prostate-specific antigen (PSA), and Ki-67 (a marker of cell proliferation) protein expression. Messenger RNA (mRNA) levels and gene amplification of Her-2-neu were examined by RNA in situ hybridization and fluorescent in situ hybridization (FISH), respectively, in a subset of 27 tumors (nine UNT, 11 TAA, and seven AI). All statistical tests were two-sided. Results: Her-2-neu protein expression was statistically significantly higher in TAA tumors than in UNT tumors with the use of two different scoring methods (P = .008 and P = .002). The proportion of Her-2-neu-positive tumors increased from the UNT group (17 of 67) to the TAA group (20 of 34) to the AI group (14 of 18) (P

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