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An immunohistochemical signature comprising PTEN, MYC, and Ki67 predicts progression in prostate cancer patients receiving adjuvant docetaxel after prostatectomy
Author(s) -
Antonarakis Emmanuel S.,
Keizman Daniel,
Zhang Zhe,
Gurel Bora,
Lotan Tamara L.,
Hicks Jessica L.,
Fedor Helen L.,
Carducci Michael A.,
De Marzo Angelo M.,
Eisenberger Mario A.
Publication year - 2012
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.27689
Subject(s) - pten , medicine , prostate cancer , oncology , immunohistochemistry , prostatectomy , univariate analysis , docetaxel , proportional hazards model , prostate , cancer , cancer research , biochemical recurrence , pi3k/akt/mtor pathway , multivariate analysis , biology , apoptosis , biochemistry
BACKGROUND: Loss of the tumor suppressor PTEN is common in prostate cancer and may have prognostic significance. The authors examined PTEN and additional protein markers in primary tumors from patients with high‐risk, localized prostate cancer who received adjuvant docetaxel in a prospective multicenter trial (TAX2501). METHODS: Fifty‐six of 77 patients enrolled in TAX2501 had primary prostatectomy specimens available for immunohistochemical analysis of PTEN, MYC, ERG, tumor protein p53 (p53), antigen KI‐67 (Ki67), and phosphorylated forms of Akt, mammalian target of rapamycin (mTOR), and S6 ribosomal protein. Protocol‐defined progression included a prostate‐specific antigen (PSA) level ≥0.4 ng/mL, radiologic/clinical recurrence, or death. Univariate and multivariable proportional hazards regression analyses were used to investigate the influence of PTEN status (and other protein markers) on progression‐free survival (PFS). RESULTS: In this exploratory, post hoc analysis, PTEN protein loss (vs presence) was observed in 61% of patients and was associated with lower preoperative PSA levels, higher clinical stage, lower Ki67 expression, the presence of p53, and the presence of ERG. In univariate analysis, the factors associated with PFS included Gleason sum, seminal vesicle invasion, PTEN status, MYC expression, and Ki67 expression. In multivariable analysis, only 3 variables emerged as independent prognostic factors for PFS: PTEN status ( P = .035), MYC expression ( P = .001), and Ki67 expression ( P < .001). A prognostic model was constructed that incorporated clinical covariates as well as information on PTEN, MYC, and Ki67. CONCLUSIONS: The current results indicated that PTEN status, MYC expression, and Ki67 expression in primary tumor samples may predict PFS more accurately than clinical factors alone in men with high‐risk prostate cancer who receive adjuvant docetaxel after prostatectomy. If validated, these hypothesis‐generating findings may have prognostic and therapeutic implications and may aid clinical trial design. Cancer 2012. © 2012 American Cancer Society.