AB114. The expression and significance of W E E 1 in renal clear cell carcinoma

Objective: To investigate the expression and significance of W E E 1 protein in renal clear cell carcinoma (RCCC), as well as the relationship between W E E 1 and biology behaviors (clinical stages, pathological grades and lymphatic metastases) of RCCC, providing evidence for diagnosis, therapy and prognosis of RCCC.

Methods: Immunohistochemical analysis (SP method), real time PCR and Western blot were used to determine the W E E 1 expression in 32 RCCCs and 25 normal renal tissues. Then the relationships between clinical stage, pathological grade, lymphatic metastases and W E E 1 expressions of RCCC were analyzed. All statistical analyses were carried out with SPSS 14.0 software. The probability of less than 5% was assumed to be statistically significant (P<0.05).

Results: The positive rate of W E E 1 expression in RCCC was 87.5% (28/32), compared with 8% (2/25) in normal tissues. W E E 1 expressions in RCCC were significantly higher than those in normal renal tissues (P<0.01). The CT value of W E E 1 mRNA expression in the renal cell carcinoma was 13.7±3.7, compared with 4.5±2.0 in normal tissues. There is significant difference between the two groups (P<0.01). Western Blot analysis indicates a significant higher expression of W E E 1 (5.2±1.5) in RCCC as compared with that (0.6±0.37) in normal tissues. In stage I, II and III-IV, the expressions of W E E 1 were 3.1±0.7, 4.7±0.9 and 6.7±0.9 respectively. The expressions of W E E 1 in stage II and III-IV were 1.5 times and 2.2 times compared with those in stage I (P<0.05). The W E E 1 expression was also closely related with pathological grade. The W E E 1 expressions in well differentiated group, moderately differentiated group and poorly differentiated group were 3.1±0.5, 4.4±0.5, and 6.4±0.9 respectively. The W E E 1 expression in moderately and poorly differentiated group were 1.75 times and 1.8 times compared with the other one (P<0.05). The W E E 1 expression was 4.3±1.1 in patients without lymph node metastasis while 6.8±0.6 in those with lymph node metastasis; The W E E 1 expression in metastasis group was 1.6 times as the other group (P<0.05). There was positive correlation between expression of W E E 1 protein and metastasis. The correlation coefficient is 0.805, (P<0.01).

Conclusions: W E E 1 expression in RCCCs higher than those in normal renal tissues, the expression of W E E 1 was much lower in the normal kidney tissue. WEE1 expression in RCCC was closely related to pathological grades, clinical stage and lymph node metastases. The W E E 1 expression in III, IV group was higher than the phase I and II. The expression in the differentiation of low and moderately differentiated groups was higher than the high group. In addition, the expression of lymph node metastasis group was higher than other groups. W E E 1 is expected to become an important biological index to evaluate RCCC metastasis and prognosis and may be a novel therapeutic target of RCCC.

Keywords: Renal clear cell carcinoma (RCCC); W E E 1; immunohistochemical; real time PCR; cell cycle; G2 arrest