Chromosomal deletions, tumor phenotype, and prognosis in prostate cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 37-37
Author(s):  
S. Minner ◽  
A. Krohn ◽  
L. Burkhardt ◽  
P. Tennstedt ◽  
R. Simon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Array Cgh ◽  
Tumor Stage ◽  
Fish Analysis ◽  
Gleason Grade ◽  
Advanced Tumor Stage ◽  
Chromosomal Deletions ◽  
Advanced Tumor ◽  
Psa Recurrence ◽  
Tumor Phenotype

37 Background: Chromosomal deletions are frequent in prostate cancer (PCa) but target genes and potential clinical significance are often unknown. This project aimed at the identification of frequent and new deletions in PCa and to study their association with tumor phenotype and PSA recurrence. Methods: Array CGH was performed on 77 advanced PCa. Deletions of interest were subsequently analyzed on a tissue microarray containing more than 2000 PCa with clinical follow-up data using fluorescence in situ hybridization (FISH). The FISH probes used included a break-apart probe for TMPRSS2-ERG and dual-labeling probes for centromere 10/PTEN and centromere 3/3p14. Results: The most frequent circumscribed deletions found by array CGH were 3p14 (including FOXP1) in 18%, 5q31 in 16%, 5q21 in 14%, 6q13 in 21%, 6q21 in 19%, 6q26 in 14%, 8p11 in 17%, 10q23 (including PTEN) in 18%, 12p13 in 14%, 13q14 in 14%, 16q24 in 22% and 21q (representing TMPRSS2-ERG fusion) in 18%. TMPRSS2-ERG fusions, PTEN and FOXP1 deletions were selected for FISH analysis. A TMPRSS2-ERG fusion was observed in 394 of 947 interpretable cases (41.6%). TMPRSS2-ERG fusion was unrelated to tumor stage, Gleason grade, and PSA recurrence. PTEN deletions were observed in 8.9% of 1844 interpretable cases and were associated with advanced tumor stage (p<0.0001), high Gleason grade (p<0.0001), and early biochemical recurrence (p<0.0001). FOXP1 deletions were seen in 5.0% of 619 cases. FOXP1 deletions were not significantly linked to tumor phenotype and outcome. Both PTEN and FOXP1 deletions were strongly linked to TMPRSS2-ERG fusions. TMPRSS2-ERG fusion positive tumors had PTEN deletions in 15.4% and FOXP1 deletions in 10.7%, while TMPRSS2-ERG fusion negative cancers had PTEN deletions in only 5.8% and FOXP1 deletions in only 2.0% of cases (p<0.0001 each). Conclusions: The TMPRSS2-ERG fusion determines a genetically distinct subgroup of prostate cancers. Our data provide no evidence for a particular clinical behaviour of TMPRSS2-ERG fusion positive cancers in radically operated patients. PTEN and FOXP1 alterations are preferentially found in TMPRSS2-ERG fusion positive cancers. Both genes may potentially be involved in pathway dysregulation in these cancers. No significant financial relationships to disclose.

Association of nuclear accumulation of p53 with ERG fusion and poor prognosis in prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 124-124
Author(s):  
Sarah Minner ◽  
Antje Krohn ◽  
Hueseyin Sirma ◽  
Ronald Simon ◽  
Markus Graefen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Poor Prognosis ◽  
Statistical Power ◽  
Tumor Stage ◽  
Nuclear Accumulation ◽  
Cancer Tissue ◽  
Positive Staining ◽  
Advanced Tumor Stage ◽  
Advanced Tumor ◽  
Psa Recurrence

124 Background: We have previously shown that nuclear accumulation of p53 is rare in prostate cancer but strongly linked to early biochemical recurrence (Schlomm et al., Modern Pathology, 2008). The current study was designed to study the association between ERG fusion and p53 in a large series of prostate cancers. Methods: A prostate cancer tissue microarray (TMA) was constructed from 4,699 radical prostatectomie specimens with histological, pathological, and clinical follow-up data. Immunohistochemistry was applied to detect nuclear p53 accumulation as a marker for defective p53 and to detect ERG expression as a surrogate for ERG gene fusion. Results: Nuclear accumulation of p53 was detected in 62/3,667 (1.7%) analyzable tissue spots. Positive staining was significantly linked to advanced tumor stage (p<0.0001), high Gleason score (p<0.0001), presence of lymph node metastases (p=0.0005), and early PSA recurrence (p<0.0001) in all cancers. ERG expression was found in 1,990/4,266 (46.6%) analyzable cancers, but was unrelated to tumor phenotype or patient prognosis. Results of both p53 and ERG were available from 3,392 tumors. Presence of nuclear p53 staining was linked to ERG fusion positive cancers: 40 (2.7%) of 1,491 ERG-positive cancers, but only 20 (1.1%) of 1,901 ERG-negative tumors showed nuclear p53 staining (p=0.0004). A Kaplan-Meier survival analysis of p53 in the subsets of 1,699 ERG positive and 1,280 ERG negative cancers revealed that nuclear p53 accumulation was strongly linked to early PSA recurrence in both subsets (p<0.0001 each). Conclusions: These data demonstrate that the poor prognosis of prostate cancer patients with nuclear p53 accumulation is independently from the ERG fusion status, but suggest a distinct biological role of p53 inactivation in ERG fusion positive cancers. The very high number of prostate cancer samples included in the TMA used in this study allows for analysis of rare events such as p53 alterations with high statistical power.

scholarly journals The independent prognostic impact of the GATA2 pioneering factor is restricted to ERG-negative prostate cancer

Tumor Biology ◽  
2019 ◽  
Vol 41 (7) ◽  
pp. 101042831882481 ◽  
Author(s):  
Franziska Büscheck ◽  
Maciej Zub ◽  
Asmus Heumann ◽  
Claudia Hube-Magg ◽  
Ronald Simon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Progression ◽  
Receptor Expression ◽  
Androgen Receptor Expression ◽  
Prognostic Impact ◽  
Gleason Grade ◽  
Advanced Tumor Stage ◽  
Normal Prostate ◽  
Advanced Tumor

GATA2 is a pioneering transcription factor governing androgen receptor expression and signaling in prostate cells. To understand the prognostic potential of GATA2 assessment in prostate cancer, we analyzed nuclear GATA2 expression on an annotated tissue microarray with 12,427 prostate cancer samples. Normal prostate glands were negative to weakly positive. GATA2 staining was found in almost all prostate cancers (95%). Strong GATA2 staining was linked to advanced tumor stage, high classical and quantitative Gleason grade (p < 0.0001 each), positive nodal stage (p = 0.0116), and early biochemical recurrence (p < 0.0001). GATA2 was linked to ERG-fusion-type cancers, with strong GATA2 staining in 29% of ERG-negative and 53% of ERG-positive cancers (p < 0.0001). Separate calculations in 3854 cancers with and 4768 cancers without TMPRSS2:ERG fusion revealed that these associations with tumor phenotype and patient outcome were largely driven by the subset of ERG-negative tumors. GATA2 expression was further linked to androgen receptor expression: Only 8% of androgen receptor-negative, but 56% of strongly androgen receptor expressing cancers had strong GATA2 expression (p < 0.0001). In conclusion, the results of our study demonstrate that increasing GATA2 levels are linked to prostate cancer progression and aggressiveness. The prognostic value of GATA2 is remarkable in ERG-negative cancers. However, the upregulation of GATA2 in ERG-positive cancers makes it unsuitable as a prognostic marker in this patient subset.

scholarly journals Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Morton Freytag ◽  
Martina Kluth ◽  
Elena Bady ◽  
Claudia Hube-Magg ◽  
Georgia Makrypidi-Fraune ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Regulatory Protein ◽  
Tumor Stage ◽  
Molecular Data ◽  
Prognostic Impact ◽  
Advanced Tumor Stage ◽  
Nuclear Staining ◽  
Prognostic Features ◽  
Advanced Tumor ◽  
The Impact

Abstract Background Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) regulate alternative splicing events of various pre-mRNAs. Some of these targets play a role in cancer-associated processes, including cytoskeleton reorganization and DNA-repair processes. This study was undertaken to estimate the impact of ESRP1 and ESRP2 alterations on prostate cancer patient prognosis. Methods A tissue microarray made from 17,747 individual cancer samples with comprehensive, pathological, clinical and molecular data was analyzed by immunohistochemistry for ESRP1 and ESRP2. Results Nuclear staining for ESRP1 was seen in 38.6% (36.0% low, 2.6% high) of 12,140 interpretable cancers and in 41.9% (36.4% low, 5.3% high) of 12,962 interpretable cancers for ESRP2. Nuclear protein expression was linked to advanced tumor stage, high Gleason score, presence of lymph node metastasis, early biochemical recurrence, and ERG-positive cancers (p < 0.0001 each). Expression of ESRPs was significantly linked to 11 (ESRP1)/9 (ESRP2) of 11 analyzed deletions in all cancers and to 8 (ESRP1)/9 (ESRP2) of 11 deletions in ERG-negative cancers portending a link to genomic instability. Combined ESRPs expression analysis suggested an additive effect and showed the worst prognosis for cancers with high ESRP1 and ESRP2 expression. Multivariate analyses revealed that the prognostic impact of ESRP1, ESRP2 and combined ESRP1/ESRP2 expression was independent of all established pre- and postoperative prognostic features. Conclusions Our data show a striking link between nuclear ESRP expression and adverse features in prostate cancer and identifies expression of ESRP1 and/or ESRP2 as independent prognostic markers with a potential for routine application.

scholarly journals The Association between Plasma Levels of Intact and Cleaved uPAR Levels and the Risk of Biochemical Recurrence after Radical Prostatectomy for Prostate Cancer

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 877
Author(s):  
Hein Vincent Stroomberg ◽  
Gitte Kristensen ◽  
Kasper Drimer Berg ◽  
Solvej Lippert ◽  
Klaus Brasso ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Plasma Levels ◽  
Biochemical Recurrence ◽  
Specific Antigen ◽  
Predictive Biomarkers ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Urokinase Plasminogen Activator Receptor ◽  
Advanced Tumor

Radical prostatectomy (RP) is a curatively intended treatment option for clinically localized non-metastatic prostate cancer (PCa). Novel biomarkers could refine treatment choice based on a better identification of men at risk of biochemical recurrence (BCR) following therapy. The urokinase plasminogen activator receptor (uPAR) system is a promising biomarker of aggressiveness in many cancers. The predictive value of uPAR after curatively intended treatment for PCa remains to be elucidated. This was a prospective evaluation of uPAR analysis in men with prostate cancer (Copenhagen uPAR prostate cancer (CuPCA) database). Risk of BCR following RP was analyzed using cumulative incidences with competing risk and tested with Gray’s test. Associations between quartile groups of uPAR levels and BCR were assessed with uni- and multivariate Cox proportional hazards. In total, 532 men were included. With more advanced tumor stage, Gleason score (GS), and prostate-specific antigen (PSA) the uPAR I–III + II–III plasma levels increased. Quartile levels of plasma uPAR I–III, I–III + II–III showed no significant association between the risk of BCR and the plasma uPAR levels in uni- and multivariate analysis. Despite increased levels of uPAR I–III + II–III in advanced tumor stage, intact and cleaved uPAR levels were not associated with BCR and are not predictive biomarkers for BCR following curatively intended treatment of PCa. It is unlikely that further studies of uPAR in RP treated patients is needed.

scholarly journals 6q deletion is frequent but unrelated to patient prognosis in breast cancer

Breast Cancer ◽  
2021 ◽  
Author(s):  
Patrick Lebok ◽  
Hannah Bönte ◽  
Martina Kluth ◽  
Christina Möller-Koop ◽  
Isabell Witzel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Stage ◽  
Proliferation Index ◽  
Fish Analysis ◽  
Prognostic Impact ◽  
Advanced Tumor Stage ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Advanced Tumor ◽  
Frequent Event

Abstract Background Deletions involving the long arm of chromosome 6 have been reported to occur in breast cancer, but little is known about the clinical relevance of this alteration. Methods We made use of a pre-existing tissue microarray with 2197 breast cancers and employed a 6q15/centromere 6 dual-labeling probe for fluorescence in situ (FISH) analysis Results Heterozygous 6q15 deletions were found in 202 (18%) of 1099 interpretable cancers, including 19% of 804 cancers of no special type (NST), 3% of 29 lobular cancers, 7% of 41 cribriform cancers, and 28% of 18 cancers with papillary features. Homozygous deletions were not detected. In the largest subset of NST tumors, 6q15 deletions were significantly linked to advanced tumor stage and high grade (p < 0.0001 each). 6q deletions were also associated with estrogen receptor negativity (p = 0.0182), high Ki67 proliferation index (p < 0.0001), amplifications of HER2 (p = 0.0159), CCND1 (p = 0.0069), and cMYC (p = 0.0411), as well as deletions of PTEN (p = 0.0003), 8p21 (p < 0.0001), and 9p21 (p = 0.0179). However, 6q15 deletion was unrelated to patient survival in all cancers, in NST cancers, or in subsets of cancers defined by the presence or absence of lymph-node metastases. Conclusion Our data demonstrate that 6q deletion is a frequent event in breast cancer that is statistically linked to unfavorable tumor phenotype and features of genomic instability. The absence of any prognostic impact argues against a clinical applicability of 6q15 deletion testing in breast cancer patients.

Hypermethylation of MCAM gene is associated with advanced tumor stage in prostate cancer

The Prostate ◽  
2008 ◽  
Vol 68 (4) ◽  
pp. 418-426 ◽  
Author(s):  
Jun-Wei Liu ◽  
Jatin K. Nagpal ◽  
Carmen Jeronimo ◽  
Ji Eun Lee ◽  
Rui Henrique ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Advanced Tumor

scholarly journals Impact of Matrix Metalloproteinase-11 Gene Polymorphisms on Biochemical Recurrence and Clinicopathological Characteristics of Prostate Cancer

2020 ◽  
Vol 17 (22) ◽  
pp. 8603
Author(s):  
Chun-Yu Hsieh ◽  
Ying-Erh Chou ◽  
Chia-Yen Lin ◽  
Shian-Shiang Wang ◽  
Ming-Hsien Chien ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Matrix Metalloproteinase ◽  
Cancer Patients ◽  
Biochemical Recurrence ◽  
Specific Antigen ◽  
Clinicopathological Characteristics ◽  
Gleason Grade ◽  
Advanced Tumor Stage ◽  
Advanced Tumor

Prostate cancer is among the most common malignant tumors worldwide. Matrix metalloproteinase (MMP)-11 is involved in extracellular matrix degradation and remodeling and plays an essential role in cancer development and metastasis. This study investigated the association of MMP-11 polymorphisms with the clinicopathological characteristics and biochemical recurrence of prostate cancer. Five single-nucleotide polymorphisms (SNPs) of the MMP-11 were analyzed in 578 patients with prostate cancer through real-time polymerase chain reaction analysis. A prostate-specific antigen level of >10 ng/mL, Gleason grade groups 4 + 5, advanced tumor stage, lymph node metastasis, invasion, and high-risk D’Amico classification were significantly associated with biochemical recurrence in the patients (p < 0.001). MMP-11 rs131451 “TC + CC” polymorphic variants were associated with advanced clinical stage (T stage; p = 0.007) and high-risk D’Amico classification (p = 0.015) in patients with biochemical recurrence. These findings demonstrate that MMP-11 polymorphisms were not associated with prostate cancer susceptibility; however, the rs131451 polymorphic variant was associated with late-stage tumors and high-risk D’Amico classification in prostate cancer patients with biochemical recurrence. Thus, the MMP-11 SNP rs131451 may contribute to the tumor development in prostate cancer patients with biochemical recurrence.

Nuclear and Cytoplasmic Expression of ErbB-4 in Prostate Cancer

2007 ◽  
Vol 22 (3) ◽  
pp. 181-185
Author(s):  
R. Ben-Yosef ◽  
D. Sarid ◽  
A. Vexler ◽  
G. Lidawi ◽  
M. Inbar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Lymph Node Involvement ◽  
Advanced Tumor Stage ◽  
Nuclear Staining ◽  
Free Survival ◽  
Advanced Tumor ◽  
Disease Free

Purpose To evaluate cytoplasmic and nuclear ErbB-4 expression in prostate cancer specimens and its association with outcome. Basic procedures Specimens of 50 prostate cancer patients were investigated for ErbB-4 overexpression using immunohistochemistry staining. Cytoplasmic and nuclear staining was graded as 0–3 according to its intensity. The prognostic parameters were tumor stage, PSA level, Gleason score, probability of positive lymph nodes (Partin's tables and Roach equation), and 5-year disease free survival (Kattan nomogram). Main findings Overexpression of ErbB-4 (≥1) was detected in 30 (60%) patients and overexpression using cytoplasmic and nuclear staining was ≥2 in 19 (38%) and 17 (34%) patients, respectively. In only one third of the specimens was there any similarity between the 2 types of staining. Advanced tumor stage, high pretreatment PSA levels and high Gleason scores were evenly distributed among the patients with low (≤1) and intermediate/high (≥2) ErbB-4 expression. The probability of lymph node involvement and 5-year disease free survival were similar in both types of staining. Principal conclusions ErbB-4 was overexpressed (cytoplasmic and nuclear staining) in approximately one third of prostate cancer patients. The rate of similarity between the 2 staining types was only 33%: overexpression was evenly distributed among intermediate/high and low risk prostate cancer patients with both staining methods.

Sign in / Sign up

Export Citation Format

Share Document