- Email: [email protected]
PD33-06 MCAM SUPPORTS THE AGGRESSIVE PHENOTYPE IN HUMAN PROSTATE CANCER
THE JOURNAL OF UROLOGYâ
Vol. 197, No. 4S, Supplement, Saturday, May 13, 2017
METHODS: Formalin-fixed paraffin embedded (FFPE) primary prostate cancer samples were obtained from the Welsh Cancer Bank. Targeted-NGS was performed using the Life Technologies Ion Torrent: Ion AmpliSeq Cancer Hotspot Panel v2 and the Ion Personal Genome Machine sequencer. The hotspot panel covers ~2800 COSMIC mutations of 50 oncogenes and tumour suppressor genes. Standard IHC techniques were also used concentrating on markers of the Wnt, PI3Kinase (PI3K) and MAP-Kinase (MAPK) oncogenic signalling pathways. RESULTS: 61 primary prostate cancer samples were sequenced, 58 from radical retropubic prostatectomy (RRP) specimens and 3 from transurethral resection of prostate (TURP) sections, with a range of Gleason Scores (GS). 21/61 (34.4%) samples harboured a mutation in a cell cycle pathway gene such as TP53 or RB1 and 3/61 (4.9%) in a DNA repair gene such as ATM. 10/61 (16.5%) of samples harboured a mutation in a gene associated with the Wnt pathway such as APC or CTNNB1. 14/61 (23.0%) of samples analysed had a mutation in a gene commonly associated with the PI3K pathway such as PTEN or AKT1. 5/61 (8.2%) had a mutation in a gene associated with the MAPK pathway such as KRAS. IHC profiles were analysed on 317 prostate samples: 73 normal and 244 cancers. There was greater expression of markers associated with Wnt, PI3K and MAPK signalling pathways in prostate cancer samples when compared to normal samples. There was greater expression in high-risk GSs with some markers associated with biochemical recurrence following RRP. Furthermore, we were able to separate low- and high-risk GS samples based on molecular profiles using markers of the Wnt, PI3K and MAPK and principle components analysis. CONCLUSIONS: Targeted NGS and IHC can identify recurrent mutations and signalling pathway aberrations within primary prostate cancer samples, which have potential to be targeted and used in routine clinical practice. In addition, the molecular signatures of low- and highrisk are different and can be separated using a combination of markers and IHC. This finding could explain the marked difference in the behaviours of these tumours types.
e595
invisible lesions on mpMRI, 5 (36%) were Gleason 3+4¼7 (Table 1). We detected high-confidence prioritized genetic mutations in 54% (14/ 26) of tumor foci, 43% (6/14) of which were in mpMRI-invisible lesions. Additionally, 64% (9/14) of lesions exhibiting prioritized mutations were Gleason 7. Notable point mutations were in APC, AR, ARID1B, ATM, ATRX, BRCA2, FAT1, MAP3K1, NF1, SPEN, SPOP, TP53, and a frameshift mutation was detected in SOX2. The expression profile of mpMRI visible and invisible lesions were similar (Figure 1). CONCLUSIONS: We found no significant difference in the molecular profile of visible and invisible cancer foci on mpMRI. However, 36% of mpMRI invisible lesions exhibited biologically significant mutations. More work is needed to further characterize the molecular basis for mpMRI prostate cancer visibility.
Source of Funding: The Urology Foundation
PD33-05 TARGETED NEXT GENERATION SEQUENCING TO CHARACTERIZE MAGNETIC RESONANCE IMAGING VISIBLE AND INVISIBLE PROSTATE CANCER: BIOLOGICAL INSIGHTS AND THERAPEUTIC IMPLICATIONS Simpa Salami, Daniel Hovelson, Aaron Udager, Matthew Lee*, Nicole Curci, Jeremy Kaplan, Arvin George, Matthew Davenport, Scott Tomlins, Ganesh Palapattu, Ann Arbor, MI INTRODUCTION AND OBJECTIVES: While multiparametric magnetic resonance imaging (mpMRI) of the prostate has improved disease detection, up to 20% of patients with negative mpMRI harbor high grade prostate cancer (PCa). In this study, we sought to characterize and compare the molecular profiles of mpMRI visible and invisible PCa. METHODS: Patients who underwent mpMRI prior to radical prostatectomy were identified for this IRB-approved study. mpMRI for each patient was reviewed by a radiologist with expertise in prostate mpMRI and histopathology reviewed by a genitourinary pathologist. Whole-mount histopathology was co-registered with axial mpMRI images. DNA and RNA were co-isolated from all tumor foci pre-identified on formalin-fixed paraffin-embedded specimens. High depth, targeted DNA and RNA next generation sequencing was performed to characterize the molecular profile of each tumor focus using the Oncomine Comprehensive Panel (DNA sequencing) and a custom targeted RNAseq panel assessing PCa relevant genes. RESULTS: A total of 26 primary tumor foci from 10 patients were analyzed. The median number of PCa foci was 3. Of the 14 (54%)
Source of Funding: None
PD33-06 MCAM SUPPORTS THE AGGRESSIVE PHENOTYPE IN HUMAN PROSTATE CANCER Eugenio Zoni, Letizia Astrologo, Bern, Switzerland; Janine Melsen, Leiden, Netherlands; Irena Klima, Joel Grosjean, Bern, Switzerland; Gabri van der Pluijm, Leiden, Netherlands; Marco G. Cecchini, Marianna Kruithof-de Julio*, George N. Thalmann, Bern, Switzerland INTRODUCTION AND OBJECTIVES: Prostate Cancer (PCa) is the most common cancer in males and the second leading cause of death from cancer in men. When PCa progress from localized disease to castration resistance, the formation of incurable metastases, primarily in the bone, is almost inevitable. Therefore, understanding the factors that regulate homing and survival of metastatic cancer cells in the bone is important for the identification of new therapeutic targets. High MCAM expression has been detected in the stroma of lytic and blastic lesions in preclinical models of PCa bone metastasis. The objective of this study is to characterize the role of MCAM in the maintenance of the aggressive phenotype in human PCa.
THE JOURNAL OF UROLOGYâ
e596
METHODS: We used shRNAs to knockdown the expression of MCAM in the lytic PC-3M-Pro4Luc2_dTomato and in the blastic C4-2B_dTomato PCa cell lines. We validated the knockdown at protein level and tested the effect with functional assays such as migration, proliferation. RT-qPCR was used to test MCAM knockdown on EMT markers. The effect of the knockdown on the maintenance of cancer stem/progenitor-like cells was measured by ALDEFLUOR. RESULTS: MCAM knockdown reduced proliferation in PC3M-Pro4Luc2_dTomato PCa cells and resulted in increased ECadherin expression. Conversely, no effect on proliferation was measured on C4-2B_dTomato cells. It has been described that metastatic human PCa cells target the hematopoietic stem cell (HSC) niche in the bone marrow at the level of an »endosteal/ osteoblast« niche and a »vascular/perivascular« niche. We set-up an in vitro model of »osteoblast niche« to study the behavior of prostate cancer cells upon co-culture with osteoblasts and to measure the resulting effects on cancer stem/progenitor-like markers. We found that MCAM is required for the osteoblast-mediated induction of ALDH activity on PCa cells and MCAM knockdown prevented the increase in the size of the ALDHhigh subpopulation in PC-3M-Pro4Luc2_dTomato, mediated by human osteoblasts. Additionally, MCAM knockdown in PCa cells co-culture with osteoblast, prevented the induction of MCAM expression by osteoblasts compared to nontargeted control. Finally, we showed that MCAM is significantly increased in the highly metastatic ALDHhigh cells and identified a new subset of ALDHhigh / MCAMhigh cells which could be depleted upon MCAM knockdown. CONCLUSIONS: We detected a new subset of ALDHhigh/ MCAMhigh cells and demonstrated that MCAM influences the maintenance of an aggressive-mesenchymal phenotype in human PCa. Therefore, MCAM represent an interesting target molecule to modulate the behavior of aggressive PCa cells. Source of Funding: SNF Grant 310030_156933
PD33-07 CCRL2 REGULATES PROSTATE CANCER ORGAN SPECIFIC METASTASIS THROUGH THE INTERACTION WITH CCR5 Chia-Ling Hsieh, Taipei, Taiwan; Kuan-Chou Chen, New Taipei, Taiwan; Shian-Ying Sung*, Taipei, Taiwan INTRODUCTION AND OBJECTIVES: To evaluate the expression level of chemokine receptors in response to chemokines released by reactive stroma, quantitative PCR to evaluate the mRNA level of chemokine receptors was performed. METHODS: To check the expression level of CCRL2, we performed qRT-PCR and western blot analysis. Cell tracking assays were performed to analyze its role in chemoattraction. Proximity ligation assays were conducted to analyze the co-localization of CCRL2 and CCR5. To analyze the role of CCRL2 in regulation of cancer cell metastasis, we conducted in vivo analysis. Stromal cell overexpressed CCL5 were inoculated in renal capsule, followed by intra-peritoneal injection of prostate cancer cell overexpressed CCRL2 to determine the organ specific metastasis. To analyze the population of cells expression CCRL2, cell sorting assays was conducted. RESULTS: We noticed the significant increasing of CCRL2 (86fold) in androgen insensitive prostate cancer cells. Knockdown of CCRL2 declined 75% of migration activities induced by CCL5, suggests CCRL2 involve in CCL5 induce cancer migratory activities. IHC analysis of CCRL2 in paired prostate cancer patients was performed and revealed increasing of CCRL2 expression in malignant prostate cancer locus, whereas no CCRL2 can be detected in the benign region of same patient. Proximity ligation assays (PLAs) of benign, high grade tumor and tissues collected from patients less than 5-year survive demonstrated the PLA signals only in the lethal progression on patients. In vivo
Vol. 197, No. 4S, Supplement, Saturday, May 13, 2017
xenograft mice model studies demonstrated the organ specific cancer metastasis can be enhanced after overexpressed CCRL2 in cancer cells. Cell sorting assays indicated that CCRL2 only expressed in less than 10% population of prostate cancer cells. Molecular analysis of CCRL2 demonstrated that CCRL2 regulated EZH2 expression in prostate cancer cells. CONCLUSIONS: Our studies indicated the increased expression of CCRL2 play a central role in cancer cell migration induced by chemokine CCL5. CCL5, secreted by bone stromal cells after interaction with dormancy cancer cell, may induce directional migration and invasion of circulating cancer cells. Clinical analyses demonstrated increased of CCRL2 in malignant prostate cancer. Inhibition of these homing mechanisms might significantly decreased cancer cell metastatic activities of AIPC patients. Source of Funding: MOST103-2320-B-038-039-MY3, MOHW105-TDU-B-212-134001
PD33-08 EXPRESSION PROFILES OF ERG AND SPINK1 IN LATENT, INCIDENTAL, AND METASTATIC PROSTATE CANCER Takahiro Kimura*, Hiroyuki Inaba, Haruhisa koide, Shun Sato, Yasutoshi Yoshiyama, Toshihiro Yamamoto, Jun Miki, Hiroyuki Takahashi, Shin Egawa, Tokyo, Japan INTRODUCTION AND OBJECTIVES: TMPRSS2:ERG fusion is the most frequent genetic event in prostate cancer (PC), resulting in ERG overexpression. In Western populations, approximately 50% of PCs express fusion products; however, our previous study showed that ERG expression was less frequent in a cohort of Japanese patients with localized PC (15/92, 16.3%). The association between ERG overexpression and the clinical behavior of PC is controversial. SPINK1 overexpression is noted in approximately 10% of patients with localized PC, mutually exclusive of ERG overexpression. Although the association of SPINK1 overexpression with an aggressive PC phenotype has been reported, its prognostic significance is unclear. PC is occasionally diagnosed at autopsy and during cystoprostatectomy for bladder cancer; most of these cases are thought to represent the latent phase of the tumor. Thus, assessment of ERG and SPINK1 expression in latent, incidental, and metastatic PC (the most aggressive form) may be useful in evaluating the association between ERG and SPINK1 expression and the biological aggressiveness of the tumor. METHODS: In total, 151 autopsies among institutional autopsy records from 2009 to 2015 and 84 cystoprostatectomy specimens were included. Each prostate gland was fixed and sliced into step sections. Ninety-eight prostate biopsy specimens from a cohort of patients who received an initial diagnosis of metastatic PC between 2003 and 2012 were investigated. ERG and SPINK1 expression was assessed by immunohistochemistry and the expression patterns were compared to clinicopathological parameters. RESULTS: PC was identified in 53/151 autopsies and 20/84 cystoprostatectomy specimens. ERG and SPINK1 expression patterns were not significantly different [4/73 (5.5%) and 5/73 (8.3%) in the latent/incidental PC cohort and 14/98 (14.3%) and 12/98 (12.2%) in the metastatic PC cohort, respectively]. SPINK1 was almost exclusively expressed in ERG-negative tumors, except in one case. In the metastatic PC cohort, ERG and SPINK1 expression patterns were not associated with age, prostate-specific antigen level, and the Gleason score. SPINK1 expression was significantly associated with a shorter time to castration-resistant PC (P¼0.0151), although ERG expression was not associated with clinical outcomes. CONCLUSIONS: ERG and SPINK1 expression was not significantly different between latent/incidental PC and metastatic PC. SPINK1 expression may be a predictor of a shorter response to androgen deprivation therapy in metastatic PC. Source of Funding: none
Vol. 197, No. 4S, Supplement, Saturday, May 13, 2017
METHODS: Formalin-fixed paraffin embedded (FFPE) primary prostate cancer samples were obtained from the Welsh Cancer Bank. Targeted-NGS was performed using the Life Technologies Ion Torrent: Ion AmpliSeq Cancer Hotspot Panel v2 and the Ion Personal Genome Machine sequencer. The hotspot panel covers ~2800 COSMIC mutations of 50 oncogenes and tumour suppressor genes. Standard IHC techniques were also used concentrating on markers of the Wnt, PI3Kinase (PI3K) and MAP-Kinase (MAPK) oncogenic signalling pathways. RESULTS: 61 primary prostate cancer samples were sequenced, 58 from radical retropubic prostatectomy (RRP) specimens and 3 from transurethral resection of prostate (TURP) sections, with a range of Gleason Scores (GS). 21/61 (34.4%) samples harboured a mutation in a cell cycle pathway gene such as TP53 or RB1 and 3/61 (4.9%) in a DNA repair gene such as ATM. 10/61 (16.5%) of samples harboured a mutation in a gene associated with the Wnt pathway such as APC or CTNNB1. 14/61 (23.0%) of samples analysed had a mutation in a gene commonly associated with the PI3K pathway such as PTEN or AKT1. 5/61 (8.2%) had a mutation in a gene associated with the MAPK pathway such as KRAS. IHC profiles were analysed on 317 prostate samples: 73 normal and 244 cancers. There was greater expression of markers associated with Wnt, PI3K and MAPK signalling pathways in prostate cancer samples when compared to normal samples. There was greater expression in high-risk GSs with some markers associated with biochemical recurrence following RRP. Furthermore, we were able to separate low- and high-risk GS samples based on molecular profiles using markers of the Wnt, PI3K and MAPK and principle components analysis. CONCLUSIONS: Targeted NGS and IHC can identify recurrent mutations and signalling pathway aberrations within primary prostate cancer samples, which have potential to be targeted and used in routine clinical practice. In addition, the molecular signatures of low- and highrisk are different and can be separated using a combination of markers and IHC. This finding could explain the marked difference in the behaviours of these tumours types.
e595
invisible lesions on mpMRI, 5 (36%) were Gleason 3+4¼7 (Table 1). We detected high-confidence prioritized genetic mutations in 54% (14/ 26) of tumor foci, 43% (6/14) of which were in mpMRI-invisible lesions. Additionally, 64% (9/14) of lesions exhibiting prioritized mutations were Gleason 7. Notable point mutations were in APC, AR, ARID1B, ATM, ATRX, BRCA2, FAT1, MAP3K1, NF1, SPEN, SPOP, TP53, and a frameshift mutation was detected in SOX2. The expression profile of mpMRI visible and invisible lesions were similar (Figure 1). CONCLUSIONS: We found no significant difference in the molecular profile of visible and invisible cancer foci on mpMRI. However, 36% of mpMRI invisible lesions exhibited biologically significant mutations. More work is needed to further characterize the molecular basis for mpMRI prostate cancer visibility.
Source of Funding: The Urology Foundation
PD33-05 TARGETED NEXT GENERATION SEQUENCING TO CHARACTERIZE MAGNETIC RESONANCE IMAGING VISIBLE AND INVISIBLE PROSTATE CANCER: BIOLOGICAL INSIGHTS AND THERAPEUTIC IMPLICATIONS Simpa Salami, Daniel Hovelson, Aaron Udager, Matthew Lee*, Nicole Curci, Jeremy Kaplan, Arvin George, Matthew Davenport, Scott Tomlins, Ganesh Palapattu, Ann Arbor, MI INTRODUCTION AND OBJECTIVES: While multiparametric magnetic resonance imaging (mpMRI) of the prostate has improved disease detection, up to 20% of patients with negative mpMRI harbor high grade prostate cancer (PCa). In this study, we sought to characterize and compare the molecular profiles of mpMRI visible and invisible PCa. METHODS: Patients who underwent mpMRI prior to radical prostatectomy were identified for this IRB-approved study. mpMRI for each patient was reviewed by a radiologist with expertise in prostate mpMRI and histopathology reviewed by a genitourinary pathologist. Whole-mount histopathology was co-registered with axial mpMRI images. DNA and RNA were co-isolated from all tumor foci pre-identified on formalin-fixed paraffin-embedded specimens. High depth, targeted DNA and RNA next generation sequencing was performed to characterize the molecular profile of each tumor focus using the Oncomine Comprehensive Panel (DNA sequencing) and a custom targeted RNAseq panel assessing PCa relevant genes. RESULTS: A total of 26 primary tumor foci from 10 patients were analyzed. The median number of PCa foci was 3. Of the 14 (54%)
Source of Funding: None
PD33-06 MCAM SUPPORTS THE AGGRESSIVE PHENOTYPE IN HUMAN PROSTATE CANCER Eugenio Zoni, Letizia Astrologo, Bern, Switzerland; Janine Melsen, Leiden, Netherlands; Irena Klima, Joel Grosjean, Bern, Switzerland; Gabri van der Pluijm, Leiden, Netherlands; Marco G. Cecchini, Marianna Kruithof-de Julio*, George N. Thalmann, Bern, Switzerland INTRODUCTION AND OBJECTIVES: Prostate Cancer (PCa) is the most common cancer in males and the second leading cause of death from cancer in men. When PCa progress from localized disease to castration resistance, the formation of incurable metastases, primarily in the bone, is almost inevitable. Therefore, understanding the factors that regulate homing and survival of metastatic cancer cells in the bone is important for the identification of new therapeutic targets. High MCAM expression has been detected in the stroma of lytic and blastic lesions in preclinical models of PCa bone metastasis. The objective of this study is to characterize the role of MCAM in the maintenance of the aggressive phenotype in human PCa.
THE JOURNAL OF UROLOGYâ
e596
METHODS: We used shRNAs to knockdown the expression of MCAM in the lytic PC-3M-Pro4Luc2_dTomato and in the blastic C4-2B_dTomato PCa cell lines. We validated the knockdown at protein level and tested the effect with functional assays such as migration, proliferation. RT-qPCR was used to test MCAM knockdown on EMT markers. The effect of the knockdown on the maintenance of cancer stem/progenitor-like cells was measured by ALDEFLUOR. RESULTS: MCAM knockdown reduced proliferation in PC3M-Pro4Luc2_dTomato PCa cells and resulted in increased ECadherin expression. Conversely, no effect on proliferation was measured on C4-2B_dTomato cells. It has been described that metastatic human PCa cells target the hematopoietic stem cell (HSC) niche in the bone marrow at the level of an »endosteal/ osteoblast« niche and a »vascular/perivascular« niche. We set-up an in vitro model of »osteoblast niche« to study the behavior of prostate cancer cells upon co-culture with osteoblasts and to measure the resulting effects on cancer stem/progenitor-like markers. We found that MCAM is required for the osteoblast-mediated induction of ALDH activity on PCa cells and MCAM knockdown prevented the increase in the size of the ALDHhigh subpopulation in PC-3M-Pro4Luc2_dTomato, mediated by human osteoblasts. Additionally, MCAM knockdown in PCa cells co-culture with osteoblast, prevented the induction of MCAM expression by osteoblasts compared to nontargeted control. Finally, we showed that MCAM is significantly increased in the highly metastatic ALDHhigh cells and identified a new subset of ALDHhigh / MCAMhigh cells which could be depleted upon MCAM knockdown. CONCLUSIONS: We detected a new subset of ALDHhigh/ MCAMhigh cells and demonstrated that MCAM influences the maintenance of an aggressive-mesenchymal phenotype in human PCa. Therefore, MCAM represent an interesting target molecule to modulate the behavior of aggressive PCa cells. Source of Funding: SNF Grant 310030_156933
PD33-07 CCRL2 REGULATES PROSTATE CANCER ORGAN SPECIFIC METASTASIS THROUGH THE INTERACTION WITH CCR5 Chia-Ling Hsieh, Taipei, Taiwan; Kuan-Chou Chen, New Taipei, Taiwan; Shian-Ying Sung*, Taipei, Taiwan INTRODUCTION AND OBJECTIVES: To evaluate the expression level of chemokine receptors in response to chemokines released by reactive stroma, quantitative PCR to evaluate the mRNA level of chemokine receptors was performed. METHODS: To check the expression level of CCRL2, we performed qRT-PCR and western blot analysis. Cell tracking assays were performed to analyze its role in chemoattraction. Proximity ligation assays were conducted to analyze the co-localization of CCRL2 and CCR5. To analyze the role of CCRL2 in regulation of cancer cell metastasis, we conducted in vivo analysis. Stromal cell overexpressed CCL5 were inoculated in renal capsule, followed by intra-peritoneal injection of prostate cancer cell overexpressed CCRL2 to determine the organ specific metastasis. To analyze the population of cells expression CCRL2, cell sorting assays was conducted. RESULTS: We noticed the significant increasing of CCRL2 (86fold) in androgen insensitive prostate cancer cells. Knockdown of CCRL2 declined 75% of migration activities induced by CCL5, suggests CCRL2 involve in CCL5 induce cancer migratory activities. IHC analysis of CCRL2 in paired prostate cancer patients was performed and revealed increasing of CCRL2 expression in malignant prostate cancer locus, whereas no CCRL2 can be detected in the benign region of same patient. Proximity ligation assays (PLAs) of benign, high grade tumor and tissues collected from patients less than 5-year survive demonstrated the PLA signals only in the lethal progression on patients. In vivo
Vol. 197, No. 4S, Supplement, Saturday, May 13, 2017
xenograft mice model studies demonstrated the organ specific cancer metastasis can be enhanced after overexpressed CCRL2 in cancer cells. Cell sorting assays indicated that CCRL2 only expressed in less than 10% population of prostate cancer cells. Molecular analysis of CCRL2 demonstrated that CCRL2 regulated EZH2 expression in prostate cancer cells. CONCLUSIONS: Our studies indicated the increased expression of CCRL2 play a central role in cancer cell migration induced by chemokine CCL5. CCL5, secreted by bone stromal cells after interaction with dormancy cancer cell, may induce directional migration and invasion of circulating cancer cells. Clinical analyses demonstrated increased of CCRL2 in malignant prostate cancer. Inhibition of these homing mechanisms might significantly decreased cancer cell metastatic activities of AIPC patients. Source of Funding: MOST103-2320-B-038-039-MY3, MOHW105-TDU-B-212-134001
PD33-08 EXPRESSION PROFILES OF ERG AND SPINK1 IN LATENT, INCIDENTAL, AND METASTATIC PROSTATE CANCER Takahiro Kimura*, Hiroyuki Inaba, Haruhisa koide, Shun Sato, Yasutoshi Yoshiyama, Toshihiro Yamamoto, Jun Miki, Hiroyuki Takahashi, Shin Egawa, Tokyo, Japan INTRODUCTION AND OBJECTIVES: TMPRSS2:ERG fusion is the most frequent genetic event in prostate cancer (PC), resulting in ERG overexpression. In Western populations, approximately 50% of PCs express fusion products; however, our previous study showed that ERG expression was less frequent in a cohort of Japanese patients with localized PC (15/92, 16.3%). The association between ERG overexpression and the clinical behavior of PC is controversial. SPINK1 overexpression is noted in approximately 10% of patients with localized PC, mutually exclusive of ERG overexpression. Although the association of SPINK1 overexpression with an aggressive PC phenotype has been reported, its prognostic significance is unclear. PC is occasionally diagnosed at autopsy and during cystoprostatectomy for bladder cancer; most of these cases are thought to represent the latent phase of the tumor. Thus, assessment of ERG and SPINK1 expression in latent, incidental, and metastatic PC (the most aggressive form) may be useful in evaluating the association between ERG and SPINK1 expression and the biological aggressiveness of the tumor. METHODS: In total, 151 autopsies among institutional autopsy records from 2009 to 2015 and 84 cystoprostatectomy specimens were included. Each prostate gland was fixed and sliced into step sections. Ninety-eight prostate biopsy specimens from a cohort of patients who received an initial diagnosis of metastatic PC between 2003 and 2012 were investigated. ERG and SPINK1 expression was assessed by immunohistochemistry and the expression patterns were compared to clinicopathological parameters. RESULTS: PC was identified in 53/151 autopsies and 20/84 cystoprostatectomy specimens. ERG and SPINK1 expression patterns were not significantly different [4/73 (5.5%) and 5/73 (8.3%) in the latent/incidental PC cohort and 14/98 (14.3%) and 12/98 (12.2%) in the metastatic PC cohort, respectively]. SPINK1 was almost exclusively expressed in ERG-negative tumors, except in one case. In the metastatic PC cohort, ERG and SPINK1 expression patterns were not associated with age, prostate-specific antigen level, and the Gleason score. SPINK1 expression was significantly associated with a shorter time to castration-resistant PC (P¼0.0151), although ERG expression was not associated with clinical outcomes. CONCLUSIONS: ERG and SPINK1 expression was not significantly different between latent/incidental PC and metastatic PC. SPINK1 expression may be a predictor of a shorter response to androgen deprivation therapy in metastatic PC. Source of Funding: none