Low RKIP expression associates with poor prognosis in bladder cancer patients

被引:17
作者
Afonso, Julieta [1 ,2 ]
Longatto-Filho, Adhemar [1 ,2 ,3 ]
Martinho, Olga [1 ,2 ]
Lobo, Francisco [4 ]
Amaro, Teresina [5 ]
Reis, Rui M. [1 ,2 ,6 ]
Santos, Lucio L. [7 ,8 ]
机构
[1] Univ Minho, Life & Hlth Sci Res Inst ICVS, Braga, Portugal
[2] ICVS 3Bs PT Govt Associate Lab, Braga, Portugal
[3] Sao Paulo State Univ, Fac Med, Lab Med Invest LIM 14, Sao Paulo, Brazil
[4] Portuguese Inst Oncol IPO, Dept Urol, P-4200072 Oporto, Portugal
[5] Portuguese Inst Oncol IPO, Expt Pathol & Therapeut Res Ctr, P-4200072 Oporto, Portugal
[6] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil
[7] Portuguese Inst Oncol IPO, Dept Surg Oncol, P-4200072 Oporto, Portugal
[8] Univ Fernando Pessoa UFP, Oporto, Portugal
关键词
Bladder cancer; Biomarkers; RKIP; Lymphovascular invasion; Prognosis; RAF KINASE INHIBITOR; NF-KAPPA-B; PROTEIN EXPRESSION; BRAF GENE; PROSTATE; METASTASIS; CARCINOMA; BREAST; INVASION; CELLS;
D O I
10.1007/s00428-013-1388-2
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Urothelial bladder cancer (UBC) is a heterogeneous type of disease. It is urgent to screen biomarkers of tumour aggressiveness in order to clarify the clinical behaviour and to personalize therapy in UBC patients. Raf kinase inhibitory protein (RKIP) is a metastasis suppressor, and its downregulation is associated with metastatic events in an increasing number of solid tumours. We evaluated the clinical and prognostic significance of RKIP expression in patients with high risk of progression UBC. Using immunohistochemistry, we determined RKIP expression levels in a series of 81 patients with high-grade pT1/pTis or muscle-invasive UBC. Staining of CD31 and D2-40 was used to assess blood and lymphatic vessels, in order to distinguish between blood and lymphatic vessel invasion (LVI). We found that 90 % of pT1/pTis tumours, 94 % of non-muscle invasive papillary tumours and 76 % of the cases without LVI occurrence expressed RKIP in > 10 % of cells. In this group, we observed a subgroup of tumours (42 %) in which the tumour centre was significantly more intensely stained than the invasion front. This heterogeneous pattern was observed in 63 % of the cases with LVI. Low RKIP expression was associated with poorer 5-year disease-free and overall survival rates, and remained as an independent prognostic factor for disease-free survival. Loss of RKIP expression may be an important prognostic factor for patients with high risk of progression bladder cancer.
引用
收藏
页码:445 / 453
页数:9
相关论文
共 62 条
[1]   The aggressiveness of urothelial carcinoma depends to a large extent on lymphovascular invasion - the prognostic contribution of related molecular markers [J].
Afonso, Julieta ;
Santos, Lucio Lara ;
Amaro, Teresina ;
Lobo, Francisco ;
Longatto-Filho, Adhemar .
HISTOPATHOLOGY, 2009, 55 (05) :514-524
[2]   Raf kinase inhibitor protein: mechanism of loss of expression and association with genomic instability [J].
Al-Mulla, F. ;
Hagan, S. ;
Al-Ali, W. ;
Jacob, S. P. ;
Behbehani, A. I. ;
Bitar, M. S. ;
Dallol, A. ;
Kolch, W. .
JOURNAL OF CLINICAL PATHOLOGY, 2008, 61 (04) :524-529
[3]   Raf kinase inhibitor protein expression in a survival analysis of colorectal cancer patients [J].
Al-Mulla, Fahd ;
Hagan, Suzanne ;
Behbehani, Abdulla I. ;
Bitar, Milad S. ;
George, Shirley S. ;
Going, James J. ;
Curto Garcia, Jorge J. ;
Scott, Lucy ;
Fyfe, Nicky ;
Murray, Graeme I. ;
Kolch, Walter .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (36) :5672-5679
[4]   RAF kinase inhibitory protein (RKIP) modulates cell cycle kinetics and motility [J].
al-Mulla, Fahd ;
Bitar, Milad S. ;
Taqi, Zainab ;
Rath, Oliver ;
Kolch, Walter .
MOLECULAR BIOSYSTEMS, 2011, 7 (03) :928-941
[5]   A New Model for Raf Kinase Inhibitory Protein Induced Chemotherapeutic Resistance [J].
Al-Mulla, Fahd ;
Bitar, Milad S. ;
Feng, Jingwei ;
Park, Sungdae ;
Yeung, Kam C. .
PLOS ONE, 2012, 7 (01)
[6]   Raf Kinase Inhibitor Protein RKIP Enhances Signaling by Glycogen Synthase Kinase-3β [J].
Al-Mulla, Fahd ;
Bitar, Milad S. ;
Al-Maghrebi, May ;
Behbehani, Abdulla I. ;
Al-Ali, Waleed ;
Rath, Oliver ;
Doyle, Brendan ;
Tan, Kit Yee ;
Pitt, Andrew ;
Kolch, Walter .
CANCER RESEARCH, 2011, 71 (04) :1334-1343
[7]  
Amin M., 2005, URINARY BLADDER CANC
[8]   Inhibition of epithelial to mesenchymal transition in metastatic prostate cancer cells by the novel proteasome inhibitor, NPI-0052: pivotal roles of Snail repression and RKIP induction [J].
Baritaki, S. ;
Chapman, A. ;
Yeung, K. ;
Spandidos, D. A. ;
Palladino, M. ;
Bonavida, B. .
ONCOGENE, 2009, 28 (40) :3573-3585
[9]   Snail is a repressor of RK1P transcription in metastatic prostate cancer cells [J].
Beach, S. ;
Tang, H. ;
Park, S. ;
Dhillon, A. S. ;
Keller, E. T. ;
Kolch, W. ;
Yeung, K. C. .
ONCOGENE, 2008, 27 (15) :2243-2248
[10]   Raf kinase inhibitor protein suppresses nuclear factor-κB-dependent cancer cell invasion through negative regulation of matrix metalloproteinase expression [J].
Beshir, Anwar B. ;
Ren, Gang ;
Magpusao, Anniefer N. ;
Barone, Lauren M. ;
Yeung, Kam C. ;
Fenteany, Gabriel .
CANCER LETTERS, 2010, 299 (02) :137-149