Protein kinase A RI-alpha predicts for prostate cancer outcome: analysis of radiation therapy oncology group trial 86-10.
OBJECTIVE
The RI-alpha regulatory subunit of protein kinase A type 1 (PKA) is constitutively overexpressed in human cancer cell lines and is associated with active cell growth and neoplastic transformation. This report examined the association between PKA expression and the endpoints of biochemical failure (BF), local failure (LF), distant metastasis (DM), cause-specific mortality (CSM), and overall mortality in men treated with radiotherapy, with or without short-term androgen deprivation in Radiation Therapy Oncology Group trial 86-10.


METHODS
Pretreatment archival diagnostic tissue samples from 80 patients were stained for PKA by immunohistochemical methods from a parent cohort of 456 cases. PKA intensity was scored manually and by image analysis. The Cox proportional hazards model for overall mortality and Fine and Gray's regression models for CSM, DM, LF and BF were then applied to determine the relationship of PKA expression to the endpoints.


RESULTS
The pretreatment characteristics of the missing and determined PKA groups were not significantly different. On univariate analyses, a high PKA staining intensity was associated with BF (image analysis, continuous variable, p = 0.022), LF (image analysis, dichotomized variable, p = 0.011), CSM (manual analysis, p = 0.037; image analysis, continuous, p = 0.014), and DM (manual analysis, p = 0.029). On multivariate analyses, the relationships to BF (image analysis, continuous, p = 0.03), LF (image analysis, dichotomized, p = 0.002), and DM remained significant (manual analysis, p = 0.018). In terms of CSM, a trend toward an association was seen (manual analysis, p = 0.08; image analysis, continuous, p = 0.09).


CONCLUSIONS
PKA overexpression was significantly related to patient outcome and is a potentially useful biomarker for identifying high-risk prostate cancer patients who might benefit from a PKA knockdown strategy.
Khor
Li-Yan
LY
Department of Radiation Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Bae
Kyounghwa
K
Al-Saleem
Tahseen
T
Hammond
Elizabeth H
EH
Grignon
David J
DJ
Sause
William T
WT
Pilepich
Miljenko V
MV
Okunieff
Paul P
PP
Sandler
Howard M
HM
Pollack
Alan
A
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000378:metabolism*; D054743:Cyclic AMP-Dependent Protein Kinase Type I / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000532:radiotherapy*; D012044:Regression Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D054743:Cyclic AMP-Dependent Protein Kinase Type I