Expression of β-tubulin isotypes in urothelial carcinoma of the bladder

被引:17
作者
Choi, Jung-Woo [1 ]
Kim, Younghye [1 ]
Lee, Ju-Han [1 ]
Kim, Young-Sik [1 ]
机构
[1] Korea Univ, Ansan Hosp, Dept Pathol, Ansan 425707, Gyeonggi Do, South Korea
关键词
Bladder cancer; Immunohistochemistry; Tubulin; Chemotherapy; CELL LUNG-CANCER; PHASE-III TRIAL; MICROTUBULE DYNAMICS; CHEMOTHERAPY; RESISTANCE; METHOTREXATE; SENSITIVITY; VINBLASTINE; DOXORUBICIN; CISPLATIN;
D O I
10.1007/s00345-012-0993-z
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Our study aims to investigate the expressions of beta-tubulin isotypes and their significances in urothelial carcinoma of the bladder (UCB) as altered expression of a specific beta-tubulin isotype is associated with chemoresistance and poor prognosis in other malignancies. Expression of beta-tubulin isotypes was retrospectively examined in 342 UCB samples obtained from 1995 to 2010 by immunohistochemistry. TUBB1 (307/342, 89.8 %) was most frequently overexpressed in the cytoplasm of UCB cases, followed by TUBB4 (101/342, 29.5 %), TUBB2 (85/342, 24.9 %), and TUBB3 (60/342, 17.5 %). TUBB1 overexpression was associated with older age (p = 0.032), high WHO grade (p = 0.001), and advanced TNM stage (p = 0.006). High levels of TUBB2 expression were associated with high WHO grade (p < 0.001), advanced TNM stage (p < 0.001), and non-papillary growth pattern (p = 0.007). TUBB3 overexpression was related to high WHO grade (p = 0.029). In univariate and multivariate survival analyses, TUBB1 overexpression was associated with poor recurrence-free survival (RFS) rates of all cases (hazard ratio 1.98, p = 0.031) and of the patients with transurethral and/or partial resection (hazard ratio 2.12, p = 0.031). TUBB2 overexpression was correlated with a short RFS of the patients with T2-T4 stages (hazard ratio 3.48, p = 0.007). TUBB3 overexpression was related to a poor RFS of the patients undergoing radical cystectomy (hazard ratio 5.90, p = 0.002). High TUBB1, TUBB2, and TUBB3 expressions are associated with unfavorable clinicopathologic factors and are independent prognostic factors for recurrence-free survival of UCB.
引用
收藏
页码:347 / 352
页数:6
相关论文
共 29 条
[1]   Phase III Trial of Vinflunine Plus Best Supportive Care Compared With Best Supportive Care Alone After a Platinum-Containing Regimen in Patients With Advanced Transitional Cell Carcinoma of the Urothelial Tract [J].
Bellmunt, Joaquim ;
Theodore, Christine ;
Demkov, Tomasz ;
Komyakov, Boris ;
Sengelov, Lisa ;
Daugaard, Gedske ;
Caty, Armelle ;
Carles, Joan ;
Jagiello-Gruszfeld, Agnieszka ;
Karyakin, Oleg ;
Delgado, Francois-Michel ;
Hurteloup, Patrick ;
Morsli, Nassim ;
Salhi, Yacine ;
Culine, Stephane ;
von der Maase, Hans .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (27) :4454-4461
[2]   Do β-tubulin mutations have a role in resistance to chemotherapy? [J].
Berrieman, HK ;
Lind, MJ ;
Cawkwell, L .
LANCET ONCOLOGY, 2004, 5 (03) :158-164
[3]   β-Tubulin-II Expression Strongly Predicts Outcome in Patients Receiving Induction Chemotherapy for Locally Advanced Squamous Carcinoma of the Head and Neck: A Companion Analysis of the TAX 324 Trial [J].
Cullen, Kevin J. ;
Schumaker, Lisa ;
Nikitakis, Nikolaos ;
Goloubeva, Olga ;
Tan, Ming ;
Sarlis, Nicholas J. ;
Haddad, Robert I. ;
Posner, Marshall R. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (36) :6222-6228
[4]  
Eble J N., 2004, World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs, P90
[5]  
Edge SB, 2010, AJCC CANC STAGING MA, P497
[6]   Class III β-tubulin overexpression is a marker of poor clinical outcome in advanced ovarian cancer patients [J].
Ferrandina, G ;
Zannoni, GF ;
Martinelli, E ;
Paglia, A ;
Gallotta, V ;
Mozzetti, S ;
Scambia, G ;
Ferlini, C .
CLINICAL CANCER RESEARCH, 2006, 12 (09) :2774-2779
[7]   Identification and Characterization of an Intermediate Taxol Binding Site Within Microtubule Nanopores and a Mechanism for Tubulin Isotype Binding Selectivity [J].
Freedman, Holly ;
Huzil, J. Torin ;
Luchko, Tyler ;
Luduena, Richard F. ;
Tuszynski, Jack A. .
JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2009, 49 (02) :424-436
[8]   Tubulin-Targeted Drug Action: Functional Significance of Class II and Class IVb β-Tubulin in Vinca Alkaloid Sensitivity [J].
Gan, Pei Pei ;
Kavallaris, Maria .
CANCER RESEARCH, 2008, 68 (23) :9817-9824
[9]   Paclitaxel-resistant human ovarian cancer cells have mutant beta-tubulins that exhibit impaired paclitaxel-driven polymerization [J].
Giannakakou, P ;
Sackett, DL ;
Kang, YK ;
Zhan, ZR ;
Buters, JTM ;
Fojo, T ;
Poruchynsky, MS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (27) :17118-17125
[10]   Tubulin modifications and their cellular functions [J].
Hammond, Jennetta W. ;
Cai, Dawen ;
Verhey, Kristen J. .
CURRENT OPINION IN CELL BIOLOGY, 2008, 20 (01) :71-76