Cell cycle regulation
|
|
|
|
|
|
|
|
p53 |
High pT stage; high grade |
|
multivariate |
multivariate |
multivariate |
1414. Ku JH, Byun SS, Jeong H, Kwak C, Kim HH, Lee SE. The role of p53 on survival of upper urinary tract urothelial carcinoma: a systematic review and meta-analysis. Clin Genitourin Cancer. 2013;11:221-8.,1515. Rey A, Lara PC, Redondo E, Valdés E, Apolinario R. Overexpression of p53 in transitional cell carcinoma of the renal pelvis and ureter. Relation to tumor proliferation and survival. Cancer. 1997;79:2178-85.,1616. Mitchell S, Mayer E, Patel A. Expression of p53 in upper urinary tract urothelial carcinoma. Nat Rev Urol. 2011;8:516-22.
|
|
Cyclins |
|
|
univariate |
|
|
1818. Liang PI, Li WM, Wang YH, Wu TF, Wu WR, Liao AC, et al. HuR cytoplasmic expression is associated with increased cyclin A expression and poor outcome with upper urinary tract urothelial carcinoma. BMC Cancer. 2012;12:611.,1919. Bogdanovic Lj, Radojevic-Skodric S, Lazic M, Bogdanovic J, Spasic D, Milenkovic S, et al. Immunohistochemical detection of cyclin E in transitional cell carcinoma. J BUON. 2011;16:727-32.
|
|
p21 |
|
|
|
|
|
2222. Sarsik B, Doganavsargil B, Simsir A, Yazici A, Pehlivanoglu B, Cal C, et al. P21 and p27 Immunoexpression in Upper Urinary Tract Urothelial Carcinomas. Pathol Oncol Res. 2016;22:839-45.
|
|
p27 |
High pT stage; high grade |
|
|
|
multivariate |
2020. Nakanishi K, Kawai T, Aida S, Kasamatsu H, Aurues T, Ikeda T. Expression of p27(Kip1) protein in transitional cell carcinoma of the upper urinary tract. Mod Pathol. 2001;14:371-6.,2222. Sarsik B, Doganavsargil B, Simsir A, Yazici A, Pehlivanoglu B, Cal C, et al. P21 and p27 Immunoexpression in Upper Urinary Tract Urothelial Carcinomas. Pathol Oncol Res. 2016;22:839-45.
|
Cell growth, proliferation and signal transduction
|
|
|
|
|
|
|
|
Ki67 |
High pT stage; high grade; LVI; sessile tumor; tumor necrosis, Cis, LN+ |
multivariate |
multivariate |
multivariate |
|
2323. Kamijima S, Tobe T, Suyama T, Ueda T, Igarashi T, Ichikawa T, et al. The prognostic value of p53, Ki-67 and matrix metalloproteinases MMP-2 and MMP-9 in transitional cell carcinoma of the renal pelvis and ureter. Int J Urol. 2005;12:941-7.,2424. Jeon HG, Jeong IG, Bae J, Lee JW, Won JK, Paik JH, et al. Expression of Ki-67 and COX-2 in patients with upper urinary tract urothelial carcinoma. Urology. 2010;76:513.e7-12.,2525. Krabbe LM, Bagrodia A, Lotan Y, Gayed BA, Darwish OM, Youssef RF, et al. Prospective analysis of Ki-67 as an independent predictor of oncologic outcomes in patients with high grade upper tract urothelial carcinoma. J Urol. 2014;191:28-34.,2626. Joung JY, Yang SO, Jeong IG, Han KS, Seo HK, Chung J, et al. Identification of immunohistochemical factors that predict the synchronous or metachronous development of bladder tumors in patients with upper urinary tract tumors. Urol Int. 2008;81:306-11.,2727. Long X, Zu X, Li Y, He W, Hu X, Tong S, et al. Epidermal Growth Factor Receptor and Ki-67 as Predictive Biomarkers Identify Patients Who Will Be More Sensitive to Intravesical Instillations for the Prevention of Bladder Cancer Recurrence after Radical Nephroureterectomy. PLoS One. 2016;11:e0166884.,2828. Krabbe LM, Bagrodia A, Haddad AQ, Kapur P, Khalil D, Hynan LS, et al. Multi-institutional validation of the predictive value of Ki-67 in patients with high grade urothelial carcinoma of the upper urinary tract. J Urol. 2015;193:1486-93.
|
|
HER-2 |
High pT stage; high grade; LVI; tumor necrosis; LN+ |
multivariate |
multivariate |
multivariate |
multivariate |
3030. Vershasselt-Crinquette M, Colin P, Ouzzane A, Gnemmi V, Robin YM, Aubert S, et al. Assessment of human epidermal growth factor receptor 2 status in urothelial carcinoma of the upper urinary tract: a study using dualcolor in situ hybridization and immunohistochemistry. Appl Immunohistochem Mol Morphol. 2012;20:363-6.,3131. Langner C, Gross C, Rehak P, Ratschek M, Rüschoff J, Zigeuner R. HER2 protein overexpression and gene amplification in upper urinary tract transitional cell carcinoma: systematic analysis applying tissue microarray technique. Urology. 2005;65:176-80.,3232. Sasaki Y, Sasaki T, Kawai T, Morikawa T, Matsusaka K, Kunita A, et al. HER2 protein overexpression and gene amplification in upper urinary tract urothelial carcinomaan analysis of 171 patients. Int J Clin Exp Pathol. 2014;7:699-708.,3333. Soria F, Moschini M, Haitel A, Wirth GJ, Karam JA, Wood CG, et al. HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC). World J Urol. 2017;35:251-9.
|
|
EGFR |
High pT stage; high grade |
multivariate |
univariate |
|
|
2727. Long X, Zu X, Li Y, He W, Hu X, Tong S, et al. Epidermal Growth Factor Receptor and Ki-67 as Predictive Biomarkers Identify Patients Who Will Be More Sensitive to Intravesical Instillations for the Prevention of Bladder Cancer Recurrence after Radical Nephroureterectomy. PLoS One. 2016;11:e0166884.,3636. Leibl S, Zigeuner R, Hutterer G, Chromecki T, Rehak P, Langner C. EGFR expression in urothelial carcinoma of the upper urinary tract is associated with disease progression and metaplastic morphology. APMIS. 2008;116:27-32.
|
|
NF-κB |
|
|
|
multivariate |
multivariate |
3838. Yeh HC, Huang CH, Yang SF, Li CC, Chang LL, Lin HH, et al. Nuclear factor-κB activation predicts an unfavourable outcome in human upper urinary tract urothelial carcinoma. BJU Int. 2010;106:1223-9.
|
Angiogenesis
|
|
|
|
|
|
|
HIF-1α |
High grade; sessile tumor |
|
multivariate |
|
multivariate |
4040. Nakanishi K, Hiroi S, Tominaga S, Aida S, Kasamatsu H, Matsuyama S, et al. Expression of hypoxia-inducible factor-1alpha protein predicts survival in patients with transitional cell carcinoma of the upper urinary tract. Clin Cancer Res. 2005;11:2583-90.
|
Vasohibin-1 |
High pT stage; high grade |
|
multivariate |
multivariate |
|
4242. Miyazaki Y, Kosaka T, Mikami S, Kikuchi E, Tanaka N, Maeda T, et al. The prognostic significance of vasohibin-1 expression in patients with upper urinary tract urothelial carcinoma. Clin Cancer Res. 2012;18:4145-53.
|
Thrombospondin-1 |
High pT stage; high grade |
|
univariate |
univariate |
|
4646. Miyata Y, Watanabe S, Kanetake H, Sakai H. Thrombospondin-1-derived 4N1K peptide expression is negatively associated with malignant aggressiveness and prognosis in urothelial carcinoma of the upper urinary tract. BMC Cancer. 2012;12:372.
|
FGFR3 |
Low pTstage; low grade |
|
|
|
|
4949. van Oers JM, Zwarthoff EC, Rehman I, Azzouzi AR, Cussenot O, Meuth M, et al. FGFR3 mutations indicate better survival in invasive upper urinary tract and bladder tumours. Eur Urol. 2009;55:650-7.,5050. Burger M, Catto J, van Oers J, Zwarthoff E, Hamdy FC, Meuth M, et al. Mutation of the FGFR3 oncogene is an independent and favorable prognostic factor for tumorspecific survival in patients with urothelial carcinoma of the upper urinary tract. Verh Dtsch Ges Pathol. 2006;90:244-52.
|
Cell differentiation
|
|
|
|
|
|
|
Uroplakin |
High pT stage; high grade |
|
|
multivariate |
|
5252. Ohtsuka Y, Kawakami S, Fujii Y, Koga F, Saito K, Ando N, et al. Loss of uroplakin III expression is associated with a poor prognosis in patients with urothelial carcinoma of the upper urinary tract. BJU Int. 2006;97:1322-6.,5353. Smith SC, Mohanty SK, Kunju LP, Chang E, Chung F, Carvalho JC, et al. Uroplakin II outperforms uroplakin III in diagnostically challenging settings. Histopathology. 2014;65:132-8.
|
Cell adhesion/EMT
|
|
|
|
|
|
|
Snail |
High pT stage; high grade; LVI |
|
multivariate |
multivariate |
|
5656. Kosaka T, Kikuchi E, Mikami S, Miyajima A, Shirotake S, Ishida M, et al. Expression of snail in upper urinary tract urothelial carcinoma: prognostic significance and implications for tumor invasion. Clin Cancer Res. 2010;16:5814-23.
|
E-cadherin |
High pT stage; high grade; LVI, tumor necrosis; Cis; LN+; sessile tumor; multifocality |
|
univariate |
univariate |
|
5858. Nakanishi K, Kawai T, Torikata C, Aurues T, Ikeda T. E-cadherin expression in upper-urinary-tract carcinoma. Int J Cancer. 1997;74:446-9.,5959. Muramaki M, Miyake H, Terakawa T, Kusuda Y, Fujisawa M. Expression profile of E-cadherin and N-cadherin in urothelial carcinoma of the upper urinary tract is associated with disease recurrence in patients undergoing nephroureterectomy. Urology. 2011;78:1443.e7-12.,6060. Favaretto RL, Bahadori A, Mathieu R, Haitel A, Grubmüller B, Margulis V, et al. Prognostic role of decreased E-cadherin expression in patients with upper tract urothelial carcinoma: a multi-institutional study. World J Urol. 2017;35:113-120.
|
N-cadherin |
High pT stage; LN+; sessile tumor |
multivariate |
multivariate |
|
|
5959. Muramaki M, Miyake H, Terakawa T, Kusuda Y, Fujisawa M. Expression profile of E-cadherin and N-cadherin in urothelial carcinoma of the upper urinary tract is associated with disease recurrence in patients undergoing nephroureterectomy. Urology. 2011;78:1443.e7-12.,6161. Abufaraj M, Moschini M, Soria F, Gust K, Özsoy M, Mathieu R, et al. Prognostic role of expression of N-cadherin in patients with upper tract urothelial carcinoma: a multi-institutional study. World J Urol. 2017;35:1073-1080.
|
Catenins |
Larger tumors (>3cm) |
|
multivariate |
multivariate |
|
6363. Reis ST, Leite KR, Mosconi Neto A, Pontes Júnior J, Viana NI, Antunes AA, et al. Immune expression of E-cadherin and α, β and γ-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas. Int Braz J Urol. 2012;38:466-73.,6464. Izquierdo L, Truan D, Petit A, Gutiérrez R, Mallofré C, Alcaraz A. Adhesion molecules alpha, beta and gamma-catenin as prognostic factors of tumour progression in upper urinary tract urothelial tumours: the role of AKT-P/GSK-3beta/betacatenin pathway. BJU Int. 2009;104:100-6.
|
MMPs |
High pT stage; high grade; LVI; LN+ |
|
multivariate |
multivariate |
univariate |
6868. Nakanishi K, Kawai T, Sato H, Aida S, Kasamatsu H, Aurues T, et al. Expression of matrix metalloproteinase-2 (MMP-2) and of membrane-type-1-matrix metalloproteinase (MT1-MMP) in transitional cell carcinoma of the upper urinary tract. Hum Pathol. 2000;31:193-200.,6969. Miyata Y, Kanda S, Nomata K, Hayashida Y, Kanetake H. Expression of metalloproteinase-2, metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 in transitional cell carcinoma of upper urinary tract: correlation with tumor stage and survival. Urology. 2004;63:602-8.,7171. Li WM, Wei YC, Huang CN, Ke HL, Li CC, Yeh HC, et al. Matrix metalloproteinase-11 as a marker of metastasis and predictor of poor survival in urothelial carcinomas. J Surg Oncol. 2016;113:700-7.
|
Apoptosis
|
|
|
|
|
|
|
Survivin |
High pT stage; LN+; LVI; tumor necrosis; sessile tumor |
|
multivariate |
multivariate |
|
7474. Jeong IG, Kim SH, Jeon HG, Kim BH, Moon KC, Lee SE, et al. Prognostic value of apoptosis-related markers in urothelial cancer of the upper urinary tract. Hum Pathol. 2009;40:668-77.,7575. Mathieu R, Klatte T, Margulis V, Karam JA, Rouprêt M, Seitz C, et al. Survivin is not an independent prognostic factor for patients with upper tract urothelial carcinoma: a multi-institutional study. Urol Oncol. 2015;33:495. e15-22.
|
Bcl-2 |
|
|
|
multivariate |
|
7979. Yoshimine S, Kikuchi E, Kosaka T, Mikami S, Miyajima A, Okada Y, et al. Prognostic significance of Bcl-xL expression and efficacy of Bcl-xL targeting therapy in urothelial carcinoma. Br J Cancer. 2013;108:2312-20.
|
Caspase |
High pT stage; high grade |
|
univariate |
univariate |
|
7474. Jeong IG, Kim SH, Jeon HG, Kim BH, Moon KC, Lee SE, et al. Prognostic value of apoptosis-related markers in urothelial cancer of the upper urinary tract. Hum Pathol. 2009;40:668-77.
|