2.2. CK20 and Bladder Cancer

Bladder tumors were the most common tumors of the urinary system, accounting for more than 95% of epithelial tumors, and the vast majority were urinary tract transitional cell carcinoma. The early symptoms of bladder cancer were unobvious, and the recurrence rate was high, so early diagnosis and treatment were very important to improve its efficacy. In recent years, new diagnosis of bladder cancer was emerging, significantly improved the diagnosis and prognosis prediction level of bladder tumor. Markers detection of bladder tumor had become a new method for the diagnosis of bladder tumors, which had important clinical significance. It was found that cytokeratin 20 (CK20) was one of the members of the family of intermediate filaments, which specifically expressed in umbrella cells of normal bladder tissue as well as bladder transitional cell carcinoma. It had high specificity and sensitivity of diagnosis of bladder cancer, and was closely related to the clinical grade, pathologic stage and metastasis of bladder tumor. So, it could be used as a marker for the diagnosis and prediction of prognosis of bladder tumor.

In normal urothelium, expression of CK20 is limited to umbrella cells. The dysregulation of CK20 expression can be used as an early event in the epithelial differentiation of Ta-stage bladder cancer. The vast majority of bladder tumor markers can appear in the urine, while CK20 is hardly expressed in normal human exfoliated cells. Since CK20 is a sensitive, rapid and specific method for detecting free cancer cells in urine, it can be widely used in the diagnosis and evaluation of bladder cancer.

In normal tissues, the expression of CK20 is restricted to cytoplasm and is often fibrous. In cancer cells, the cytokeratin polarity is lost, the arrangement is disordered, and the distribution is dispersed. CK20 may accumulate in the cell membrane or nuclear membrane, which is dotted or blocky. Strong staining of CK20 indicates that the synthesis of intermediate filaments is active, and tumor cells are highly motility, invasive and metastatic, and prone to metastasis. Studies have suggested that p53 is the main indicator of tumor cell proliferation, and CK20 is the main indicator of tumor cell micrometastasis. The high expression of p53 and CK20 promotes the proliferation and division of cancer cells and accelerates the micrometastasis of bladder tumor cells, which together lead to the invasion and metastasis of bladder cancer. Because CK20 is expressed in primary and metastatic urinary tract cell carcinoma, CK20 is not expressed in normal human peripheral blood and bone marrow. Therefore, it can be diagnosed by detecting the expression of CK20 in peripheral blood. Metastasis has certain clinical value for judging prognosis and guiding treatment. CK20 positive in peripheral blood suggests early dissemination of urinary tract transitional cell carcinoma, indicating a poor prognosis. Detection of lymph node metastasis is also an important prognostic factor in the assessment of progression-free survival in patients with bladder cancer. The use of RT-PCR to detect CK20 to determine lymph node metastasis is a highly sensitive and specific method that differs from classical pathology. More than one-third of CK20 expression is positive in metastatic lymph nodes outside the standard lymph node dissection area; in prostate and breast cancer, CK20 can be used to determine the source of the primary tumor and whether bone metastasis occurs. CK20 has positive implications for early detection of bladder cancer metastases. The expression of CK20 is associated with tumor recurrence and disease-specific survival. The urinary tract tumor with normal CK20 expression has a lower recurrence rate than CK20 staining abnormality. The abnormal staining status of CK20 may indicate bladder cancer recurrence. Therefore, CK20 can be used as a prognostic factor for bladder cancer, and combined with pathological grade and clinical stage to improve the accuracy of prognosis in patients with bladder cancer.  

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