Evaluation of nuclear factor κB and chemokine receptor CXCR4 co-expression in patients with prostate cancer in the Radiation Therapy Oncology Group (RTOG) 8610.

Meena Okera, Kyoungwha Bae, Eric Bernstein, Liang Cheng, Colleen Lawton, Harvey Wolkov, Alan Pollack, Adam Dicker, Howard Sandler, Christopher J Sweeney
Author Information
  1. Meena Okera: Department of Medicine, Royal Adelaide Hospital, Adelaide, Australia.

Abstract

OBJECTIVE: To determine the frequency of nuclear factor κB (NFκB) and the chemokine receptor CXCR4 co-expression in prostate cancer specimens from men with locally advanced disease.
PATIENTS AND METHODS: Paraffin-embedded samples from patients enrolled on the Radiation Therapy Oncology Group (RTOG) 8610 trial underwent immunohistochemical staining for NFκB and CXCR4. The amount of NFκB and CXCR4 was scored by a 'blinded' pathologist for the percentage of cells stained (0-100%) and staining intensity (0-3 +). Cox proportional hazard models were used for overall survival and disease-free survival to examine if NFκB and/or CXCR4 expression were associated with patient outcomes with and without adjustment for covariates.
RESULTS: Available material and successful staining allowed NFκB and CXCR4 status to be determined for 55 and 63 patients, respectively. Both NFκB and CXCR4 status were available for 51 patients. Of these, 53% were 2/3 + for cytoplasmic NFκB staining and 56% were 2/3 + for CXCR4. In all, 18 of the 51 patients were 2/3 + for both NFκB and CXCR4 (P = 0.129). Ten of 11 patients with 3 + NFκB had 2/3 + CXCR4 (P= 0.004). In this small study, neither NFκB nor CXCR4 were associated with prostate cancer outcomes.
CONCLUSIONS: High NFκB expression is associated with CXCR4 expression and they are co-expressed in about one third of patients with clinically localized prostate cancer. Larger studies to accurately determine the frequency of co-expression and prognostic utility of NFκB and CXCR4 alone and in combination are warranted.

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Grants

  1. CA-101984-01/NCI NIH HHS
  2. CA-006927/NCI NIH HHS
  3. R01 CA101984-01/NCI NIH HHS
  4. R01 CA101984/NCI NIH HHS
  5. P30 CA006927/NCI NIH HHS

MeSH Term

Aged
Aged, 80 and over
Clinical Trials, Phase III as Topic
Follow-Up Studies
Humans
Male
Middle Aged
NF-kappa B
Prostatic Neoplasms
Randomized Controlled Trials as Topic
Receptors, CXCR4
Retrospective Studies

Chemicals

NF-kappa B
Receptors, CXCR4

Word Cloud

Created with Highcharts 10.0.0CXCR4NFκBpatients+prostatecancerstaining2/3co-expressionexpressionassociateddeterminefrequencynuclearfactorκBchemokinereceptorRadiationTherapyOncologyGroupRTOG8610survivaloutcomesstatus510OBJECTIVE:specimensmenlocallyadvanceddiseasePATIENTSANDMETHODS:Paraffin-embeddedsamplesenrolledtrialunderwentimmunohistochemicalamountscored'blinded'pathologistpercentagecellsstained0-100%intensity0-3Coxproportionalhazardmodelsusedoveralldisease-freeexamineand/orpatientwithoutadjustmentcovariatesRESULTS:Availablematerialsuccessfulalloweddetermined5563respectivelyavailable53%cytoplasmic56%18P=129Ten113P=004smallstudyneitherCONCLUSIONS:Highco-expressedonethirdclinicallylocalizedLargerstudiesaccuratelyprognosticutilityalonecombinationwarrantedEvaluation

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