Immunohistochemical expression of c-Myc in patients with urinary bladder transitional cell carcinoma and correlation with tumor grade, stage and lymph node metastasis

Charalampos Fragkoulis, Georgios Ntoumas, Georgios Papadopoulos, Akrivi Kostopoulou, Theodosia Choreftaki, Konstantinos Ntoumas


Introduction: c-Myc is a proto-oncogene located on human
chromosome 8 and it is a member of the Myc family. It encodes
a transcriptional factor which regulates the expression of approximately
10-15% of human genes, having a crucial role in
cell growth, differentiation, cellular metabolism, apoptosis
and cell transformation. The aim of this study is to correlate the
expression of c-Myc in patients suffering from urinary bladder
transitional cell carcinoma (BCa) with tumor grade, stage and
lymph node metastasis.
Material and Methods: Formalin fixed, paraffin embedded
tissue samples were obtained from 54 consecutive patients
who underwent transurethral resection or radical cystectomy as
treatment for BCa. Immunohistochemistry was performed using
c-Myc monoclonal antibody and c-Myc expression was then
correlated to tumor stage, grade and lymph node metastasis.
Results: From a total of 54 patients, 42 (77.8%) presented with
c-Myc positive staining and 12 (22.2%) with c-Myc negative. In
the c-Myc positive group, 28 patients (66.7%) had low grade tumor and 33 (78.6%) presented with non-muscle invasive
disease (p<0,05). In the c-Myc negative group, 10 patients
(83.3%) had high grade disease and 8 (66.7%) presented with
muscle invasive disease (p<0,05). Lymph node metastasis was
evaluated in 17 patients who underwent radical cystectomy.
As a result, 5 had lymph node metastasis 4 of them presenting
with c-Myc negative staining (p<0,05).
Conclusion: In our study, c-Myc negative staining was associated
with higher grade and higher stage. On the contrary the
majority of c-Myc positive tumors were of low grade and non
-muscle invasive. In patients who underwent cystectomy c-Myc
negative staining was associated with lymph node disease.


urinary bladder;TCC;c-Myc;prognosis

Full Text:



Irani J, Motter N, Ribal Caparros J, et al. New trends in bladder

cancer management. Eur Urol 2007;6(4):388-395.

Abdollah F, Gandaglia G, Thuret R, et al. Incidence, survival and

mortality rates of stage-specific bladder cancer in United States:

a trend analysis. Cancer Epidemiol 2013;37(3):219-25.

Babjuk M, Burger M, Zigeuner R, et al; members of the EAU Guidelines

Panel on Non-muscle-invasive bladder cancer. Guidelines

on Non-muscle-invasive bladder cancer (Ta, T1 and CIS). Edition

presented at the EAU Annual Congress Madrid 2015. ISBN 978-


Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the

treatment of invasive bladder cancer: long-term results in 1,054

patients. J Clin Oncol 2001;19(3):666-75.

Stenzl A, Nagele U, Kuczyk M, et al. Cystectomy: technical considerations

in male and female patients. EAU Update Series 2005;3:138-46.

Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nat Rev Cancer

; 8(12):976-990.

Zachary E, Stine Z, Walton E, et al. MYC, Metabolism, and Cancer.

Cancer Discov 2015; 5(10):1024-1039.

Miller D, Thomas S, et al. c-Myc and Cancer Metabolism. Clin Cancer

Res 2012; 18(20): 5546-5553.

Kalkat M, De Melo J, et al. MYC Deregulation in Primary Human

Cancers. Genes (Basel) 2017; 8(6): 151.

Li Y, Liu H, Lai C, et al. The Lin28/let-7a/c-Myc pathway plays a

role in non-muscle invasive bladder cancer. Cell Tissue Res. 2013


Watters AD, Latif Z, Forsyth A, et al. Genetic aberrations of

c-myc and CCND1 in the development of invasive bladder cancer.

Br Jour of Canc 2002;87(6):654-658.

Sauter G, Carroll P, Moch H, et al. c-myc copy number gains in

bladder cancer detected by fluorescence in situ hybridization. Am

J Pathol 1995;146(5):1131-9.

Zaharieva B, Simon R, Ruiz C, Oeggerli M, et al. High-throughput

tissue microarray analysis of CMYC amplificationin urinary bladder

cancer. Int J Cancer. 2005;117(6):952-6.

Schmitz-Dräger BJ, Schulz WA, Jürgens B, et al. c-myc in bladder

cancer. Clinical findings and analysis of mechanism. Urol

Res. 1997;25 Suppl 1:S45-9.

Massari F, Bria E, Ciccarese C, et al. Prognostic Value of Beta-Tubulin-

and c-Myc in Muscle Invasive Urothelial Carcinoma of the

Bladder. PLoS One. 2015;10(6):e0127908.