Clinical Significance of Cytokeratin 19 and Cytokeratin 20 in

Clinical Significance of Cytokeratin 19 and Cytokeratin 20 in

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Unformatted text preview: The Chinese-German Journal of Clinical Oncology DOI 10.1007/s10330-004-0353-6 Apr. 2006, Vol. 5, No. 2 P132–P134 Clinical Significance of Cytokeratin 19 and Cytokeratin 20 in Predicting Recurrence of Bladder Transitional Cell Carcinoma ZHANG Huiping, YANG Weimin, YE Zhangqun, CHEN Chunlian, and YU Xiao Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China Received: 31 December 2004 / Revised: 10 May 2005 / Accepted: 17 November 2005 Abstract Objective: To investigate the expressions of cytokeratin 19 (CK19) and cytokeratin 20 (CK20) in bladder transitional cell carcinoma (TCC) and their clinical significance. Methods: The expression of CK19 and CK20 was detected in 54 cases of TCC by immunohistochemical methods and image processing techniques. Results: The expression of CK19 and CK20 was significantly stronger in the recurrent group than in the non-recurrent group (P <0.01, P <0.001, respectively). Conclusion: The expression of CK19 and CK20 was obviously related with biological behaviors of TCC, suggesting that CK19 and CK20 could be used to predict the recurrence of TCC. Key words: cytokeratin 19; cytokeratin 20; bladder transitional cell carcinoma; tumor marker Bladder transitional cell carcinoma (TCC) represents a spectrum of disease defined by different recurrence and progression rates. Although the prognosis of low-grade superficial carcinoma is usually good, high-grade papillary or invasive urothelial carcinoma has much higher risk of progression. Further study of biologic markers might allow a better estimation of biologic behaviors of different tumors. Cystoscopy remains the standard method for detecting the majority of cases. However, for its invasiveness, new diagnostic methods have been considered[1] . As is well known, the coordinated expression of the cytokeratins was specific to cells or tissues. In many disease states, these expression modes can vary with differentiation or proliferation of the cells[2] . In this study, the expression of cytokeratin 19 (CK19) and CK20 was detected in order to explore their relations with bladder transitional cell carcinoma (TCC), searching for a new non-invasive technique for preoperative prediction and postoperative monitoring. follow-up of 16–26 months. Normal mucosa and stroma of bladder was obtained from 8 cases as control when receiving suprapubic prostatectomy. All samples were fixed with 10% formaldehyde solution and routinely embedded in paraffin for later use. Methods The samples were first subjected to Envision system staining. The slices were treated with antibody CK19 (M0342, 1:100, Antibody Diagnostica, USA) and CK20 (M0343, 1:50, Antibody Diagnostica, USA) at 37 ◦C for 30 min. After treatment with DAKO Envision TM kit at 37 ◦ C for 30 min and DAB, the slices were counterstained with haematine, dehydrated, and treated with xylene, and sealed. Criteria The average absorbency (A) of the cells positive for CK19 and CK20 staining in TCC and control group was determined by analyzing 5 visual fields randomly (×40 hp), using real colorful pathologic image analysis system of CMIAS (Beijing University of Aeronautics and Astronautics, China). A values indicated the number of the positive cells (large value representing the strong expression). Statistical analysis SPSS11.5 software was employed to analyze all data. Materials and methods Study objects Surgically removed and pathologically confirmed samples from 54 TCC patients were collected. Among them, 15 had no recurrence and 39 had recurrence during a Correspondence to : ZHANG Huiping. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Email: Results The relation between CK19 expression and tumor recurrence was shown in Fig. 1. ZHANG Huiping et al.: Clinical Significance of Cytokeratin 19 and Cytokeratin 20 in Predicting 133 Fig. 1 The relation between CK19 expression and tumor recurrence Fig. 2 The relation between CK20 expression and tumor recurrence The relation between CK20 expression and tumor recurrence was shown in Fig. 2. There was significant difference in the CK19 or CK20 expression between normal, non-recurrent group and recurrent group (P <0.01, P <0.001, respectively). The expression of CK19 and CK20 was significantly stronger in the recurrent group than in the normal and non-recurrent group. It was concluded that the abnormal expression of CK19 and CK20 was closely associated with recurrence of TCC. Discussion CK is the mark of epithelium differentiation and part of the intermediate filament of cell framework of all mammals. CK19 is a minimum member of CK family. In malignant epithelial cell cancer, the activated protease that accelerates cell degradation makes a great of cytokeratins fragment release into the blood. In our research, the CK19 expression was weaker in the normal and non-recurrent group than in recurrent group (P <0.01), indicating that the CK19 expression was closely related with tumor recurrence. Therefore we considered that CK19 might be an effective biological marker, and CK19 expression together with patients’ condition could help us choose suitable treatments: radical surgery, transurethral electroresection, or adjuvant intravesical chemotherapy. Benjamin et al had analyzed CK19 concentrations in 325 urine samples, including 152 patients presenting with hematuria or irritative voiding symptoms (group 1), 107 patients who were under surveillance after undergoing transurethral resection of bladder carcinoma (group 2), 46 patients with urinary tract pathological changes other than bladder carcinoma (group 3), and 20 healthy participants (group 4). The authors concluded that the urinary CYFRA 21–1 assay was a useful test for non-invasive detection of bladder carcinoma and for surveillance of patients who had been treated with BCG previously[3] . Eman et al thought CK 19 might be used as additional markers for assessment of bladder cancer patients[4] . CK20 was first isolated and identified by Moll et al in 1990[5]. Our research indicated that CK20 expression was weaker in specimens of normal bladder mucosa and nonrecurrent group than in recurrent group (P <0.001), indicating that CK20 expression was closely related to TCC recurrence. David et al performed a retrospective study 134 ZHANG Huiping et al.: Clinical Significance of Cytokeratin 19 and Cytokeratin 20 in Predicting on 120 patients with low-grade papillary bladder tumors (45 neoplasms of low malignant potential and 75 G1 carcinoma) totally, and the mean follow-up was 76.6 months (ranging from 36 to 168 months). CK20 showed an obvious statistical correlation (P <0.001) by univariate studies with both the predication of disease recurrence and recurrence-free interval over the patients treated merely with adjuvant intravesical chemotherapy[6]. In the study of Rotem et al, RT-PCR was performed with specific primers for the amplification of CK20 in urine sample. The data indicated that CK20 expression was correlated with recurrence of TCC[7] . In Christoph’s research, the author presumed that CK 20 might be an excellent and sensitive marker for tumor monitoring and routine follow-up in patients with transitional cell carcinoma[8]. As we know, the course of TCC is long, and recurrence rate is high, and the prognosis is closely related with TCC recurrence, so it is very important to find a proper tumor mark to foresee the recurrence of TCC. With the help of tumor markers, we can decide to choose partial resection, adjuvant intravesical chemotherapy or total cystectomy and finally improve patients’ living quality. In the study, we concluded that the biologic feature of TCC was reflected by different expression of CK19 and CK20. CK19 and CK20 had theoretical evidence to the application in the clinics of TCC. Hereby, the measurements of CK19 and CK20 in urine provide a more objective and direct help for choice of treatment plan, postoperative monitoring, and prognosis forecast for patients. They can also be an independent marker that indicates tumor recurrence. However, so for, no tumor marker can completely replace cystoscopy and biopsy. Whether independent application of CK19 and CK20, or CK19 and CK20 combined with bladder ultrasound or urinary cytology can replace cystoscopye and biopsy is not known, maybe this needs a great deal of cases to study in the future. References 1. Ramazan Sekeroglu M, Aydin S, Dulger H, et al. Diagnostic value of cytokeratin-18 as a tumor marker in bladder cancer. Clin Biochem, 2002, 35: 327–331. 2. Chandler JS, Calnek D, Quaroni A. Identification and characterization of rat intestinal keratins. Molecular cloning of cDNAs encoding cytokeratins 8, 19, and a new 49-kDa type I cytokeratin (cytokeratin 21) expressed by differentiated intestinal epithelial cell. J Biol Chem, 1991, 266: 11932–11938. 3. Nisman B, Barak V, Shapiro A, et al. Evaluation of urine cyfra 21-1 for the detection of primary and recurrent bladder carcinoma.Cancer, 2004, 94: 2914–2912. 4. El-Salahy EM. Evaluation of cytokeratin-19 & cytokeratin-20 and interleukin-6 in Egyptian bladder cancer patients. Clinical Biochemistry, 2002, 35: 607–613. 5. Moll R, Schiller DL, Franke WW, et al. Identification of protein IT of the intestinal cytoskeleton as a novel type I cytokeratin with unusual properties and expression patterns. J Cell Biol, 1990, 111: 567–580. 6. Ramos D, Navarro S, Villamon R, et al. Cytokeratin expression patterns in low-grade papillary urothelial neoplasms of the urinary bladder. Cancer, 2003, 97: 1876– 1883. 7. Rotem D, Cassel A, Lindenfeld N, et al. Urinary cytokeratin 20 as a marker for transitional cell carcinoma. Eur urol, 2000, 37: 601–604. 8. Christoph F, Muller M, Schostak M, et al. Quantitative detection of cytokeratin 20 mRNA expression in bladder carcinoma by real-time reverse transcriptase-polymerase chain reaction. Urology, 2004, 64: 157–161. ...
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