Evaluation of Urine NMP22 Point-of-Care Test for the Screening of Bladder Cancer

Chun Hwa Ihm; Ji Myung Kim; Yong-Hak Sohn

doi:10.3343/kjlm.2007.27.2.106

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Ihm, Kim, and Sohn: Evaluation of Urine NMP22 Point-of-Care Test for the Screening of Bladder Cancer

Original Article

Korean J Leg Med 2007;27(2):106-110.

Published online: 10 February 2007

DOI: https://doi.org/10.3343/kjlm.2007.27.2.106

Evaluation of Urine NMP22 Point-of-Care Test for the Screening of Bladder Cancer

Chun Hwa Ihm, M.D.¹, Ji Myung Kim, M.D.¹, Yong-Hak Sohn, M.D.²

¹Department of Laboratory Medicine, Eulji University School of Medicine, Daejeon, Korea

²The Armed Forces Health Services School, Daejeon, Korea

Received 24 October 2006 Revised 2 February 2007 Accepted 5 February 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Screening of high-risk patients using bladder tumor markers can offer an advantage of early detection and saving medical costs. For these purpose many tumor markers have been developed to supplement invasive cystoscopy. Our study evaluated the NMP22 point-of-care test (NMP22 POCT), which is one of the tumor makers, comparing with the standard urine cytology for the diagnosis of bladder cancer.

Methods

From January to September 2005, 232 patients who had undergone a cystoscopy due to bladder cancer associated symptoms including hematuria and dysuria were enrolled in this study. Urine specimens were collected for NMP22 POCT and cytology. NMP22 POCT and urine cytology were compared for sensitivity and specificity. In addition, we evaluated urine stick test and microscopy to explain some false-positive results in NMP22 POCT.

Results

Superficial transitional cell carcinoma was diagnosed in 10 patients. The sensitivity of NMP22 test was 60% (95% confidence interval [CI], 26.2–87.8%), whereas that of cytology was 33.3% (95% CI, 7.5–70.1%); however, the difference was not significant. The specificity of NMP22 test was 69.8% (95% CI, 63.3–75.8%), compared with 99.0% (95% CI, 96.5–99.9%) for cytology (P<0.001). The presence of microscopic RBCs in urine specimen was significantly associated with the lower specificity of NMP22 POCT (P=0.02).

Conclusions

NMP22 POCT was significantly less specific than urine cytology. To be useful as a bladder cancer screening test, the NMP22 test should have a higher specificity.

Keywords: Bladder cancer, Nuclear Matrix Protein 22 (NMP22), Tumor marker, Point-of-care test

References

1. Heney NM, Ahmed S, Flanagan MJ, Frable W, Corder MP, Hafermann MD, et al. Superficial bladder cancer: progression and recurrence. J Urol. 1983; 130:1083–6.

2. Hudson MA, Herr HW. Carcinoma in situ of the bladder. J Urol. 1995; 153:564–72.

3. Lokeshwar VB, Habuchi T, Grossman HB, Murphy WM, Hautmann SH, Hemstreet GP 3rd, et al. Bladder tumor markers beyond cytology: International Consensus Panel on bladder tumor markers. Urology. 2005; 66:35–63.

4. Malik SN, Murphy WM. Monitoring patients for bladder neoplasms: what can be expected of urinary cytology consultations in clinical practice. Urology. 1999; 54:62–6.

5. Bassi P, De Marco V, De Lisa A, Mancini M, Pinto F, Bertoloni R, et al. Non-invasive diagnostic tests for bladder cancer: a review of the literature. Urol Int. 2005; 75:193–200.

6. Quek ML, Sanderson K, Daneshmand S, Stein JP. New molecular markers for bladder cancer detection. Curr Opin Urol. 2004; 14:259–64.

7. Miyanaga N, Akaza H, Ishikawa S, Ohtani M, Noguchi R, Kawai K, et al. Clinical evaluation of nuclear matrix protein 22 (NMP22) in urine as a novel marker for urothelial cancer. Eur Urol. 1997; 31:163–8.

8. Glas AS, Roos D, Deutekom M, Zwinderman AH, Bossuyt PM, Kurth KH. Tumor markers in the diagnosis of primary bladder cancer. A systematic review. J Urol. 2003; 169:1975–82.

9. Grossman HB, Messing E, Soloway M, Tomera K, Katz G, Berger Y, et al. Detection of bladder cancer using a point-of-care proteomic assay. JAMA. 2005; 293:810–6.

10. Moonen PM, Kiemeney LA, Witjes JA. Urinary NMP22 BladderChek test in the disgnosis of superficial bladder cancer. Eur Urol. 2005; 48:951–6.

11. Fleming ID, Cooper JS, editors. AJCC Cancer Staging Manual. 5th ed.New York: Springer;1997.

12. Kim YH, Cho WJ, Hong KS, Koo HS, Shim BS, Kwon SW. Evaluation of the usefulness of immediate-cytospin wright-stained urine cytology in the screeing and monitoring of bladder cancer. Korean J Lab Med. 2003; 23:164–9.

13. Kwon DH, Hong SJ. The clinical utility of BTA TRAK, BTA stat, NMP22 and urine cytology in the diagnosis of bladder cancer: a comparative study. Korean J Urol. 2003; 44:721–6.

14. Park JO, Moon DG, Cheon J, Kim JJ, Yoon DK. Urinary NMP (nuclear matrix protein)22 in screening and post-treatment follow-up of bladder cancer. Korean J Urol. 1999; 40:551–6.

15. Atsu N, Ekici S, Oge O O, Ergen A, Hascelik G, Ozen H. False-positive results of the NMP22 test due to hematuria. J Urol. 2002; 167:555–8.

16. Ponsky LE, Sharma S, Pandrangi L, Kedia S, Nelson D, Agarwal A, et al. Screening and monitoring for bladder cancer: refining the use of NMP22. J Urol. 2001; 166:75–8.

17. Grossman HB, Soloway M, Messing E, Katz G, Stein B, Kassabian V, et al. Surveilance for recurrent bladder cancer using a point-of-care proteomic assay. JAMA. 2006; 295:299–305.

Table 1.

Baseline characteristics of the study patients

	Benign disease (n=222)	Urinary tract cancer (n=10)	Total (N=232)
Age, year
Mean (SD)	50.6 (11.6)	60.4 (15.5)	51.1 (11.9)
Range	20–84	27–78	20–84
Sex, No. (%) of patients
Male	114 (51.4)	9 (90.0)	123 (53.0)
Female	108 (48.6)	1 (10.0)	109 (47.0)

Table 2.

Comparison of NMP 22 POCT assay and urine cytology for sensitivity, specificity, and positive and negative predictive values

	NMP22 POCT	Cytology	P-value
Sensitivity, % (95% CI)	60.0 (26.2–87.8)	33.3 (7.5–70.1)	NS
According to the Stage
Ta	40.0 (2/5)^*	25.0 (1/4)^*
T1	80.0 (4/5)^*	40.0 (2/5)^*
According to the Grade
Low	25.0 (1/4)^*	0.0 (0/3)^*
Medium	66.7 (2/3)^*	33.3 (1/3)^*
High	100.0 (3/3)^*	66.7 (2/3)^*
Specificity, % (95% CI)	69.8 (63.3–75.8)	99.0 (96.5–99.9)	<0.001
Positive predictive value, % (95% CI)	8.3 (3.4–18.5)	60.0 (14.7–94.7)	NS
Negative predictive value, % (95% CI)	97.5 (93.7–99.3)	97.1 (93.8–98.9)	NS

^* No. with positive test result/Tested No. with Bladder Cancer.

Abbreviations: POCT, point-of-care test; CI, Confidence interval; NS, not significant.

Table 3.

Comparison of NMP22 POCT assay and urine cytology (K aggrement=0.07)

		Urine Cytology
		Positive result	Negative result
NMP22 POCT	Positive result	4 (3)^*	63 (3)^*
	Negative result	1 (0)^*	143 (3)^*

^* The number of true cancer patients confirmed by tissue biopsy.

Table 4.

Evaluation of factors influencing the specificity of NMP22 POCT assay in non-bladder cancer patients

	No. Patients with NMP 22 POCT negaitive/No. Patients tested with urine strip	Specificity (%)	P-value
Urine Strip analysis^*
Occult Blood
Negative	14/16	87.5	0.09
Positive	90/140	64.3
Glucose
Negative	100/149	67.1	0.58
Positive	4/7	57.1
Protein
Negative	100/147	68.0	0.16
Positive	4/9	44.4
Leukocyte
Negative	83/119	69.7	0.14
Positive	21/37	56.8
Microscopic analysis
Microscopic RBC
≤4/HPF	42/53	79.2	0.02
>4/HPF	62/103	60.2
Microscopic WBC
≤4/HPF	97/142	68.3	0.17
>4/HPF	7/14	50.0
Epithelial cell
<4/HPF	97/144	67.4	0.52
≥4/HPF	7/12	58.3
Overall	104/156	66.7

^* Urobilinogen, nitrite, bilirubin, and ketone were not involved in this analysis because of less than 5 positive results.

Abbreviations: POCT, point-of-care test; HPF, high power field.

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