132XPA-210 - A NEW PROLIFERATION MARKER DETERMINESLOCALLY ADVANCED PROSTATE CANCER AND IS APREDICTOR OF BIOCHEMICAL RECURRENCE

Stefan Aufderklamm*, Tuebingen, Germany; Joerg Hennenlotter,David Schilling, Tilman Todenhoefer, T. Germany; Saladin Alloussi,Georgios Gakis, Ulrich Vogel, Ursula Kuehs, Valentina Gerber,Tuebingen, Germany; Joachim Hevler, San Diego, CA; Arnulf Stenzl,Christian Schwentner, Tuebingen, Germany

INTRODUCTION AND OBJECTIVES: XPA-210 is a peptideproliferation marker derived from thymidine kinase 1 (TK1). TK1 hasbeen reported to be of clinical significance in several cancer entities(e.g. breast, lung and bladder cancer). However, nothing is yet knownabout the significance of XPA-210 in prostate cancer (PC). Aim of thepresent study was to determine the applicability of XPA-210 for diag-nostic and prognostic purposes in PC.

METHODS: Paraffin embedded tumor and corresponding be-nign tissue from 111 patients (Median age 65 years, Median PSA value8.9, Median Gleason score 6, 75xT2 and 36xT�2, 5xN1) who under-went radical prostatectomy between January 2003 and February 2004were constructed to a tissue microarray (TMA) and stained immuno-histochemically for XPA-210. Staining was quantitatively given as apercentage of positive cells per 100 cells. Results were correlated topathological and clinical patient data using the Wilcoxon-Kruskall-Wallis tests and linear regression analyses. Expressions in tumortissues were correlated to the time of biochemical recurrence by theKaplan-Meier method.

RESULTS: Mean staining score was 0.51 (Median 0.3) and0.14 (0.08) for tumor and benign tissue, respectively (p�0.0001).Tumor staining score was significantly associated with PSA values(p�0.05), Gleason score �6/�6 (p�0.0001) and organ-confinement(T2/T�3) (p�0.002). When looking at the time to recurrence, increas-ing XPA-210 expression scores were significantly correlated with ashorter time to biochemical relapse (p�0.003).

CONCLUSIONS: XPA-210 allows for the differentiation of can-cerous and normal prostatic tissue in diagnostic terms. Moreover,associations with classical parameters of PC progression point out aprognostic significance, especially in predicting biochemical recur-rence. These data confirm the applicability of XPA-210 in PC-patientsin terms of tissue-based diagnosis and as a progression marker.Hence, XPA-210 may be an additional tool to facilitate appropriatepatient selection for local therapy or active surveillance.

Source of Funding: None

133EVALUATION OF PTEN AND TMPRSS2-ERGABNORMALITIES IN PROSTATE CANCER BY FISHAND IMMUNOHISTOCHEMISTRY TO ADDRESSINTRA- AND INTER- TISSUE HETEROGENEITY ANDDISEASE PROGRESSION

Anthony Joshua*, Andrew Evans, Toronto, Canada; Jeremy Squire,Maisa Yoshimoto, Olga Ludkovski, Kingston, Canada;Shyh-Han Tan, Albert Dobi, Bungo Furusato, Gyorgy Petrovics,Shiv Srivastava, Rockville, MD; Isabell Sesterhenn, Washington, DC

INTRODUCTION AND OBJECTIVES: Introduction and Objec-tive: Gene fusions involving the ERG oncogene and deletions of thePTEN tumor suppressor gene are frequent alterations in prostatecancer. Recent reports highlighted the cooperation of these two path-ways in prostate cancer progression using mouse models and humantumors. We recently developed a monoclonal antibody (CPDR ERG-MAb) that specifically recognizes the ERG oncoprotein in human pros-tate tumors. The objective of this study was to determine the frequencyof ERG positive prostate cancer by immunohistochemistry (IHC) com-pared to ERG gene fusion frequency by fluorescent in situ hybridization(FISH), their association with PTEN deletion, and correlation withclinico-pathological parameters of disease progression.

METHODS: Methods: A tissue microarray (TMA) was con-structed from 142 radical prostatectomy (RP) specimens with usualacinar-type prostate carcinoma obtained at University Health Network(UHN) between 2001 and 2002 comprising 742 spots. The TMA wasconstructed using up to six 0.6 mm donor cores from each RP speci-men. In cases of multi focal and bilateral carcinoma, 3 donor coreswere obtained from the largest foci in each lobe. Different Gleasonpatterns were also sampled within each focus. Standard clinical fol-low-up data, representing 7-9 years of follow-up, were compiled foreach case using a UHN RP clinical database.

RESULTS: Results: Of the 742 cores, analysis was performedin 536 evaluable cores. Concordance between the ERG IHC andTMPRSS2 FISH in this multi-sampled TMA was 71%. Heterogeneity ofthe PTEN locus was widespread both within tumor foci and betweenfoci. The assay methodology influenced overall results. For example,FISH analysis showed wild type (wt) PTEN and wt ERG in 48% oftumor specimens in comparison to 31% by PTEN FISH and ERG IHC.Higher association of PTEN deletion rate was noted in ERG IHCpositive tumors. Of note, higher frequency of homozygous PTENdeletions associated with the ERG IHC positive tumors in comparisonto ERG negative tumors.

CONCLUSIONS: Conclusions: Comparison of FISH and IHCbased assays to analyze ERG alterations in the prostate tumors needcontinued evaluations in independent studies. PTEN interaction withERG status may reveal mechanistic insights in disease progression.Further validation studies are needed.

Source of Funding: Funding: This work was supported by theCPDR Program HU0001�04C�1502.

134DIFFERENTIAL EXPRESSION OF INTERLEUKIN-13 INPROSTATE CANCER

Chunyu Wang*, Yang Yu, Houston, TX

INTRODUCTION AND OBJECTIVES: Interleukin-13 (IL-13), amember of the interleukin superfamily, encodes an immuno-regulatorycytokine involved in B-cell maturation and differentiation, thereby inhib-its the production of pro-inflammatory cytokines and chemokines. Inthis study, we investigated the expression of IL-13 in prostate cancercell lines and tissue specimens, and assessed the potential implicationof IL-13 in the pathogenesis of prostate cancer.

METHODS: Q-RT-PCR and enzyme-linked immunosorbent as-say (ELISA) was used to analyze IL-13 expression in a panel ofprostate cell lines, including normal prostate epithelial cell line RWPE-1and prostate cancer cell lines (LNCaP, 22Rv1, DU-145, PC-3). Immu-nohistochemistry (IHC) staining was used to examine IL-13 expressionand hormone receptor status in prostate tumor specimens (N�80). Thespecimens were also microdissected by laser capture microdissection(LCM) to obtain cancerous and non-cancerous tissues. IL-13 expres-sion was analyzed in malignant and adjacent non-malignant regionsfrom the same patient. To assess the function of IL-13, 22Rv1 cellswere treated with IL-13 and cell proliferation and migration were ana-lyzed by MTS assay and Boyden chamber assay, respectively.

RESULTS: IL-13 expression was significantly higher in prostatecancer cell lines compared to non-cancerous RWPE-1 cell line. Com-parison between prostate carcinoma specimen and correspondingtumor-free tissue from the same patient revealed that IL-13 expressionwas significantly higher in malignant areas than in non-malignantregions (P�0.001). In functional assays, IL-13 treatment induced epi-thelial-mesenchymal transition and promoted cell migration, but hadlittle effect on cell proliferation. The effect of IL-13 could be inhibited byits specific neutralizing antibody.

CONCLUSIONS: The differential expression of IL-13 may beassociated with prostate cancer. IL-13 plays an important role inprostate cancer progression by enhancing cell migration and invasion.Therefore, IL-13 may serve as a novel biomarker and a candidatetherapeutic target for prostate cancer.

Source of Funding: None

e56 THE JOURNAL OF UROLOGY� Vol. 185, No. 4S, Supplement, Sunday, May 15, 2011