Korean J Urol.  2011 Dec;52(12):815-818.

Pilot Study of the Clinical Significance of Serum and Urinary HER-2/neu Protein in Bladder Cancer Patients

• Kim TS
• Rhew HY
• Hwang HY

Abstract

PURPOSE
HER-2/neu overexpression is documented in some bladder cancers. To our knowledge, there are no current studies evaluating urine HER-2/neu levels. Therefore, we examined the clinical significance of serum and urine HER-2/neu protein in bladder cancer.
MATERIALS AND METHODS
Urothelial bladder carcinoma patients (n=38, including 31 men and 7 women) and healthy controls (n=25, including 20 men and 5 women) were included in the study. Urine cytology and serum and urine HER-2/neu levels were measured before the transurethral resection of bladder tumor procedure. Prognostic factors including tumor stage, histologic grade, tumor size, multiplicity, and preoperative urine cytology and their association with urinary HER-2/neu were analyzed by simple and multiple regression analyses.
RESULTS
There was no significant difference in serum HER-2/neu between the two groups (p=0.489). The mean urinary HER-2/neu was 7,586.82 relative luminescence unit (RLU) in bladder cancer patients and 4,245.84 RLU in healthy controls. The mean RLU values of urinary HER-2/neu in the bladder cancer patient group were significantly higher than in healthy controls (p=0.012). An receiver operating characteristic curve was generated, and using the cutoff value of > or =4,800 RLU of urinary HER-2/neu, 71.1% sensitivity and 84.0% specificity were obtained. Among the clinical factors, only positive preoperative urine cytology samples were associated with urinary HER-2/neu levels by both simple and multiple regression analyses.
CONCLUSIONS
Bladder cancer patients demonstrated significantly higher urinary HER-2/neu than did healthy controls. These findings suggest that urinary HER-2/neu may be valuable as a new urinary marker. The application of urinary HER-2/neu needs additional investigation.

Keyword

HER-2 protein; Sensitivity and specificity; Serum; Urinary bladder neoplasms

MeSH Terms

Humans
Luminescence
Male
Pilot Projects
ROC Curve
Sensitivity and Specificity
Urinary Bladder
Urinary Bladder Neoplasms

Figure

• 

  FIG. 1 ROC curve for urinary HER-2/neu. Using the cutoff value of ≥4,800 RLU of urinary HER-2/neu, 71.1% sensitivity and 84.0% specificity were obtained. ROC: receiver operating characteristic, RLU: relative luminescence unit.

Reference

1. Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, et al. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature. 1986. 319:230–234.

2. Coombs LM, Pigott DA, Sweeney E, Proctor AJ, Eydmann ME, Parkinson C, et al. Amplification and over-expression of c-erbB-2 in transitional cell carcinoma of the urinary bladder. Br J Cancer. 1991. 63:601–608.

3. Moriyama M, Akiyama T, Yamamoto T, Kawamoto T, Kato T, Sato K, et al. Expression of c-erbB-2 gene product in urinary bladder cancer. J Urol. 1991. 145:423–427.

4. Sato K, Moriyama M, Mori S, Saito M, Watanuki T, Terada K, et al. An immunohistological evaluation of C-erbB-2 gene product in patients with urinary bladder carcinoma. Cancer. 1992. 70:2493–2498.

5. Coogan CL, Estrada CR, Kapur S, Bloom KJ. HER-2/neu protein overexpression and gene amplification in human transitional cell carcinoma of the bladder. Urology. 2004. 63:786–790.

6. Kim SW, Chung HS, Lee SJ, Lee JY, Cho YH, Yoon MS, et al. Amplification and overexpression of c-erbB2/neu in bladder tumor using real-time quantitative PCR with TaqMan detection system. Korean J Urol. 2001. 42:924–933.

7. Shim HY, Woo YN. Immunohistochemical expression of ras p21 and HER-2/neu oncoprotein in transitional cell carcinoma of the bladder. Korean J Urol. 1995. 36:1315–1322.

8. Andersen TI, Paus E, Nesland JM, McKenzie SJ, Børresen AL. Detection of c-erbB-2 related protein in sera from breast cancer patients. Relationship to ERBB2 gene amplification and c-erbB-2 protein overexpression in tumour. Acta Oncol. 1995. 34:499–504.

9. Osaki T, Mitsudomi T, Oyama T, Nakanishi R, Yasumoto K. Serum level and tissue expression of c-erbB-2 protein in lung adenocarcinoma. Chest. 1995. 108:157–162.

10. Tsigris C, Karayiannakis AJ, Zbar A, Syrigos KN, Baibas N, Diamantis T, et al. Clinical significance of serum and urinary c-erbB-2 levels in colorectal cancer. Cancer Lett. 2002. 184:215–222.

11. Kono K, Naganuma H, Sekikawa T, Amemiya H, Takahashi A, Iizuka H, et al. Serum level of HER-2/neu in patients with gastric cancer: correlation with HER-2/neu overexpression in gastric carcinoma tissue. Tumour Biol. 2000. 21:139–144.

12. Tsigris C, Karayiannakis AJ, Syrigos KN, Zbar A, Diamantis T, Kalahanis N, et al. Clinical significance of soluble c-erbB-2 levels in the serum and urine of patients with gastric cancer. Anticancer Res. 2002. 22:3061–3065.

13. Tambo M, Higashihara E, Terado Y, Nutahara K, Okegawa T. Comparison of serum HER2/neu with immunohistochemical HER2/neu expression for the prediction of biochemical progression in metastatic prostate cancer. Int J Urol. 2009. 16:369–374.

14. Jalali Nadoushan MR, Taheri T, Jouian N, Zaeri F. Overexpression of HER-2/neu oncogene and transitional cell carcinoma of bladder. Urol J. 2007. 4:151–154.

15. Mori S, Mori Y, Mukaiyama T, Yamada Y, Sonobe Y, Matsushita H, et al. In vitro and in vivo release of soluble erbB-2 protein from human carcinoma cells. Jpn J Cancer Res. 1990. 81:489–494.

16. Pupa SM, Ménard S, Morelli D, Pozzi B, De Palo G, Colnaghi MI. The extracellular domain of the c-erbB-2 oncoprotein is released from tumor cells by proteolytic cleavage. Oncogene. 1993. 8:2917–2923.

17. Ecke TH, Schlechte HH, Schulze G, Lenk SV, Loening SA. Four tumour markers for urinary bladder cancer--tissue polypeptide antigen (TPA), HER-2/neu (ERB B2), urokinase-type plasminogen activator receptor (uPAR) and TP53 mutation. Anticancer Res. 2005. 25:635–641.

18. Tilki D, Burger M, Dalbagni G, Grossman HB, Hakenberg OW, Palou J, et al. Urine markers for detection and surveillance of non-muscle-invasive bladder cancer. Eur Urol. 2011. 60:484–492.