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MP-07.02: Bcl-2, bax expression in prostate carcinogenesis
MODERATED POSTER SESSIONS
try in 123 paraffin-embedded ccRCC specimens. The clinical significance of these markers in relation to disease-specific survival (DSS) was analyzed. Results: CAIX and VEGF expression correlated inversely (p⫽0.0045). According to univariate analysis, low-level staining for CAIX was associated with decreased survival (p⬍0.0001), whereas low-level staining for VEGF was associated with increased survival (p⫽0.0008). More specifically, the expression of CAIX significantly stratified the survival of patients with high tumor stage (p⬍0.0001), low tumor stage (p⫽0.0065), tumor grade 1-2 (p⬍0.0001), metastasis (p⫽0.0022), no metastasis (p⬍0.0001), ECOG-PS⫽0 (p⬍0.0001) and that of VEGF was able significantly to predict survival in patients with tumor grade 1-2 (p⫽0.0009), high tumor stage (p⫽0.0023), metastasis (p⫽0.0016), no metastasis (p⫽0.0400), ECOG-PS⫽0 (p⫽0.0008). Multivariate Cox regression analysis showed that tumor stage (p⫽0.0047) and staining for CAIX (p⫽0.0002) or VEGF (p⫽0.0047) were independent prognostic factors for DSS. The expression of the CAIX and VEGF was incorporated into a single prognostic marker. On multivariate analysis stepwise the co-expression was independent prognostic factors for DSS (p⬍0.0001). Conclusions: The expression of CAIX and VEGF independently and then as a co-expression were independent predictors of DSS for ccRCC that are useful in survival prediction and targeted therapeutic strategies for patients with ccRCC.
MP-17: Prostate Cancer: Basic Research, Markers Wednesday, September 5 10:15-12:15 MP-17.01 Identification of biomarker for androgen independence in prostate cancer Ohno Y, Ohori M, Tachibana M, Akimoto S, Yoshioka K, Hatano T, Sakamoto N, Gondo T, Nakagami Y, Horiguchi Y Tokyo Medical University, Tokyo, Japan Introduction: Despite recent progress in cancer therapy, androgen independence continues to be a major obstacle in the treatment of patients with prostate cancer. The purpose of this study is to investigate the biomarker for androgen independence in prostate cancer by using a proteomic approach.
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Methods: The preliminary study included 15 patients with histologically diagnosed prostate cancer. The mean age was 75.6 years (range: 64 to 88 years), and the median serum prostate-specific antigen (PSA) value was 55.6 ng/ml (range: 2.7 to 630 ng/ml). All patients received hormonal therapy as an initial treatment. The median follow-up period was 30 months (range: 21 to 36 months). Serum samples were collected prior to prostate biopsy and when the PSA value decreased to ⬍0.1 ng/ml after hormonal therapy. The samples were analyzed by two-dimensional liquid chromatography/tandem mass spectrometry. Using the Mascot search engine, the peptide m/z values were searched against a human subset in the SwissProt database for protein identification. Furthermore, the serum concentrations of the identified proteins were measured for validating the results of the proteomic analysis. Results: Eighteen proteins were identified as differentially expressed proteins in relation to hormonal therapy by proteomic analysis; these included transferrin (Tf), transthyretin (TTR), apolipoprotein A1 precursor (APOA1), and tumor necrosis factor receptor (TNFR). The serum concentrations of Tf, TTR, and APOA1 increased after treatment; in particular, the concentration of APOA1 increased significantly (pretreatment, 130.1 ⫾ 22.2 mg/dl; post-treatment, 148 ⫾ 19.8 mg/dl; p ⫽ 0.0261). The concentration of TNFR did not change after treatment. During the course of treatment, 6 patients showed continuous elevation in the serum PSA values. There was no correlation between the change in the serum concentrations of these proteins and the PSA elevation. However, the pretreatment concentration of TTR in patients with elevated PSA was 21.47 ⫾ 4.67 mg/dl; this was significantly lower than that in patients in the hormone sensitive state -27.93 ⫾ 2.37 mg/dl (p ⬍0.05). Conclusions: The results indicate that the pretreatment TTR value may be a novel predictor of the hormone-refractory state in patients with prostate cancer. MP-07.02 Bcl-2, bax expression in prostate carcinogenesis Mitropoulou G1, Georgalis A2, Tsakanika K1, Rempelakos A2, Apostolikas N3, Thanos A2, Panotopoulou E4 1 Sismanoglio Hospital, Microbiology Department; 2Saint Savas Hospital, Urology Department; 3Saint Savas Hospital, Pathology Department; 4Saint Savas Hospital, Biology Department, Athens Greece
Introduction & Objectives: Deregulation of molecular mechanisms involved in the regulation of programmed cell death may be important for the loss of normal cell growth in prostate carcinogenesis. The expression of anti-apoptotic bcl-2, proapoptotic bax gene and bcl-2/bax ratio plays a crucial role in cancer progression. In this study, we investigated the pattern of expression of bcl-2, bax genes and bcl2/bax ration in benign prostatic hyperplasia and prostate cancer. Material & Methods: Paraffin embedded tissues from 50 patients with bening prostatic hyperplasia and 50 with prostate carcinoma were examined with molecular techniques (RT-PCR and Multiplex PCR) and immunohistochemical analysis. The statistical analysis was performed with x2 Pearson’s and Fischer exact test. Results: In benign prostatic hyperplasia, bcl-2 was seen in 36% (18/50) of the cases and bax in 62% (31/50) of the cases by molecular analysis. By immunohistochemical analysis, 20% (10/50) of the cases showed bcl-2 and 72% (36/50) bax. In prostate cancer, bcl-2 was witnessed in 12% (6/50) of the cases and bax in 24% (12/50). By molecular analysis and by immunohistochemical analysis, 10% (5/50) of the cases showed bcl-2 and 22% (11/ 50) saws bax. The bcl-2/bax ratio was determined 0.28 for benign prostatic hyperplasia and 0.45 for prostate cancer (P value⬍0,001). Conclusions: Our data showed significant differences in the pattern of bcl-2, bax expression between benign prostatic hyperplasia and prostate cancer. These results implicate a role for bcl-2/bax ratio as a potential predictive marker of prostate carcinogenesis and therapeutic response. Abstract Withdrawn MP-17.04 Chemokine receptor CXCR4 expression and prognosis in patients with metastatic prostate cancer Akashi T1,2, Koizumi K2, Tsuneyama K3, Saiki I2,4, Takano Y3, Fuse H1 1 Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research; 2Division of Pathogenic Biochemistry, Department of Bioscience, Institute of Natural Medicine; 3 Department of Pathology; 4The 21st Century COE Program, University of Toyama, Toyama, Japan Introduction: Chemokine receptor CXCR4 has been reported to be aberrantly expressed in human cancers and also has
UROLOGY 70 (Supplment 3A), September 2007
try in 123 paraffin-embedded ccRCC specimens. The clinical significance of these markers in relation to disease-specific survival (DSS) was analyzed. Results: CAIX and VEGF expression correlated inversely (p⫽0.0045). According to univariate analysis, low-level staining for CAIX was associated with decreased survival (p⬍0.0001), whereas low-level staining for VEGF was associated with increased survival (p⫽0.0008). More specifically, the expression of CAIX significantly stratified the survival of patients with high tumor stage (p⬍0.0001), low tumor stage (p⫽0.0065), tumor grade 1-2 (p⬍0.0001), metastasis (p⫽0.0022), no metastasis (p⬍0.0001), ECOG-PS⫽0 (p⬍0.0001) and that of VEGF was able significantly to predict survival in patients with tumor grade 1-2 (p⫽0.0009), high tumor stage (p⫽0.0023), metastasis (p⫽0.0016), no metastasis (p⫽0.0400), ECOG-PS⫽0 (p⫽0.0008). Multivariate Cox regression analysis showed that tumor stage (p⫽0.0047) and staining for CAIX (p⫽0.0002) or VEGF (p⫽0.0047) were independent prognostic factors for DSS. The expression of the CAIX and VEGF was incorporated into a single prognostic marker. On multivariate analysis stepwise the co-expression was independent prognostic factors for DSS (p⬍0.0001). Conclusions: The expression of CAIX and VEGF independently and then as a co-expression were independent predictors of DSS for ccRCC that are useful in survival prediction and targeted therapeutic strategies for patients with ccRCC.
MP-17: Prostate Cancer: Basic Research, Markers Wednesday, September 5 10:15-12:15 MP-17.01 Identification of biomarker for androgen independence in prostate cancer Ohno Y, Ohori M, Tachibana M, Akimoto S, Yoshioka K, Hatano T, Sakamoto N, Gondo T, Nakagami Y, Horiguchi Y Tokyo Medical University, Tokyo, Japan Introduction: Despite recent progress in cancer therapy, androgen independence continues to be a major obstacle in the treatment of patients with prostate cancer. The purpose of this study is to investigate the biomarker for androgen independence in prostate cancer by using a proteomic approach.
130
Methods: The preliminary study included 15 patients with histologically diagnosed prostate cancer. The mean age was 75.6 years (range: 64 to 88 years), and the median serum prostate-specific antigen (PSA) value was 55.6 ng/ml (range: 2.7 to 630 ng/ml). All patients received hormonal therapy as an initial treatment. The median follow-up period was 30 months (range: 21 to 36 months). Serum samples were collected prior to prostate biopsy and when the PSA value decreased to ⬍0.1 ng/ml after hormonal therapy. The samples were analyzed by two-dimensional liquid chromatography/tandem mass spectrometry. Using the Mascot search engine, the peptide m/z values were searched against a human subset in the SwissProt database for protein identification. Furthermore, the serum concentrations of the identified proteins were measured for validating the results of the proteomic analysis. Results: Eighteen proteins were identified as differentially expressed proteins in relation to hormonal therapy by proteomic analysis; these included transferrin (Tf), transthyretin (TTR), apolipoprotein A1 precursor (APOA1), and tumor necrosis factor receptor (TNFR). The serum concentrations of Tf, TTR, and APOA1 increased after treatment; in particular, the concentration of APOA1 increased significantly (pretreatment, 130.1 ⫾ 22.2 mg/dl; post-treatment, 148 ⫾ 19.8 mg/dl; p ⫽ 0.0261). The concentration of TNFR did not change after treatment. During the course of treatment, 6 patients showed continuous elevation in the serum PSA values. There was no correlation between the change in the serum concentrations of these proteins and the PSA elevation. However, the pretreatment concentration of TTR in patients with elevated PSA was 21.47 ⫾ 4.67 mg/dl; this was significantly lower than that in patients in the hormone sensitive state -27.93 ⫾ 2.37 mg/dl (p ⬍0.05). Conclusions: The results indicate that the pretreatment TTR value may be a novel predictor of the hormone-refractory state in patients with prostate cancer. MP-07.02 Bcl-2, bax expression in prostate carcinogenesis Mitropoulou G1, Georgalis A2, Tsakanika K1, Rempelakos A2, Apostolikas N3, Thanos A2, Panotopoulou E4 1 Sismanoglio Hospital, Microbiology Department; 2Saint Savas Hospital, Urology Department; 3Saint Savas Hospital, Pathology Department; 4Saint Savas Hospital, Biology Department, Athens Greece
Introduction & Objectives: Deregulation of molecular mechanisms involved in the regulation of programmed cell death may be important for the loss of normal cell growth in prostate carcinogenesis. The expression of anti-apoptotic bcl-2, proapoptotic bax gene and bcl-2/bax ratio plays a crucial role in cancer progression. In this study, we investigated the pattern of expression of bcl-2, bax genes and bcl2/bax ration in benign prostatic hyperplasia and prostate cancer. Material & Methods: Paraffin embedded tissues from 50 patients with bening prostatic hyperplasia and 50 with prostate carcinoma were examined with molecular techniques (RT-PCR and Multiplex PCR) and immunohistochemical analysis. The statistical analysis was performed with x2 Pearson’s and Fischer exact test. Results: In benign prostatic hyperplasia, bcl-2 was seen in 36% (18/50) of the cases and bax in 62% (31/50) of the cases by molecular analysis. By immunohistochemical analysis, 20% (10/50) of the cases showed bcl-2 and 72% (36/50) bax. In prostate cancer, bcl-2 was witnessed in 12% (6/50) of the cases and bax in 24% (12/50). By molecular analysis and by immunohistochemical analysis, 10% (5/50) of the cases showed bcl-2 and 22% (11/ 50) saws bax. The bcl-2/bax ratio was determined 0.28 for benign prostatic hyperplasia and 0.45 for prostate cancer (P value⬍0,001). Conclusions: Our data showed significant differences in the pattern of bcl-2, bax expression between benign prostatic hyperplasia and prostate cancer. These results implicate a role for bcl-2/bax ratio as a potential predictive marker of prostate carcinogenesis and therapeutic response. Abstract Withdrawn MP-17.04 Chemokine receptor CXCR4 expression and prognosis in patients with metastatic prostate cancer Akashi T1,2, Koizumi K2, Tsuneyama K3, Saiki I2,4, Takano Y3, Fuse H1 1 Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research; 2Division of Pathogenic Biochemistry, Department of Bioscience, Institute of Natural Medicine; 3 Department of Pathology; 4The 21st Century COE Program, University of Toyama, Toyama, Japan Introduction: Chemokine receptor CXCR4 has been reported to be aberrantly expressed in human cancers and also has
UROLOGY 70 (Supplment 3A), September 2007