A comprehensive analysis of CDC20 overexpression in common malignant tumors from multiple organs: its correlation with tumor grade and stage.

High expression of cell division cycle 20 homolog (CDC20), a key component of the spindle assembly checkpoint (SAC), has been reported in various malignancies and plays a vital role in tumorigenesis and progression. The goal of this study was to evaluate the utility of CDC20 immunostaining in a wide range of malignant tumors. CDC20 immunohistochemistry was evaluated in normal tissues and compared to the most frequently occurring malignant tumors in these tissues (bladder, breast, cervical, colonic, endometrial, gastric, head and neck, liver, lung, ovarian, pancreatic, prostatic, renal, thyroid carcinomas, and testicular seminoma). Normal/non-neoplastic tissues showed positive CDC20 expression in 19.44 % of all examined cases. CDC20 staining was negative in normal and non-neoplastic tissues from the bladder, cervix, liver, stomach, and thyroid. From the all malignant tumors examined 55.7 % showed high CDC20 expression while low expression was found in 44.3 %. High expression of CDC20 was associated with high tumor grade in the bladder (p = 0.027), cervical (p = 0.032), colonic (p = 0.026), endometrial (p = 0.016), gastric (p = 0.033), liver (p = 0.028), ovarian (p = 0.044), prostatic (p = 0.040), and renal (p = 0.048) carcinomas. There was a significant correlation between high CDC20 expression and advanced tumor stage in carcinoma of the breast, colon, endometrium, and prostate (p = 0.021, p = 0.040, p = 0.047, p = 0.031, respectively). CDC20 expression may be useful as a biomarker of tumor prognosis and as a therapeutic target of human cancer.

Correlation of NQO1 and Nrf2 in Female Genital Tract Cancer and Their Precancerous Lesions (Cervix, Endometrium and Ovary).

BACKGROUND: NAD (P) H/quinone oxidoreductase 1 (NQO1) is a metabolizing enzyme that detoxifies chemical stressors and antioxidants. Nuclear factor erythroid 2-related factor 2 (NrF2) is an important transcriptional activator involved in the cellular defense mechanisms against oxidative stress. METHODS: The immunohistochemical expression of NQO1 and Nrf2 in 80 cervical, 80 endometrial and 100 ovarian specimens with different lesions was studied. Then we study the relation of both NQO1 and Nrf2 expression and clinicopathological features of carcinoma cases. RESULTS: Immunohistochemical stain showed that NQO1 and Nrf2 were highly expressed in carcinoma compared with normal and precancerous lesions. Significant positive correlations were found between the mean expression of NQO1 and Nrf2 in different lesions. Moreover, there was significant correlation between the high level of NQO1 and Nrf2 expression and high tumor grade in cervical and endometrial carcinoma cases. Nrf2 expression was significant with advanced stage in endometrial and ovarian carcinomas. CONCLUSIONS: NQO1 and Nrf2 might be new biomarkers for early diagnosis and prognostic evaluation as well as being targets for therapy in patients with tumors in female genital tract.

Activated eosinophils upregulate the metastasis suppressor molecule E-cadherin on prostate tumor cells.

Cell adhesion molecules (CAMs) play an important role in cancer metastasis by facilitating attachment to vascular endothelia, invasion and spread into secondary tissue sites. We have shown that activated eosinophils (EosA) inhibited the growth of prostate cancer (Pca) cells in vitro. In the present study, we examined the ability of EosA 24 hr conditioned supernatants (EosAcs) to modulate the expression of ICAM-1, VCAM-1, ELAM-1, E-cadherin and N-cadherin expression on human Pca cell lines, Du-145 and PC-3 by flow cytometry. TNF-alpha, IL-10 and IL-12 were also evaluated. ICAM-1, expressed on PC-3 and DU 145 cells, was enhanced by TNF-alpha and IL-10. ELAM-1 was present on DU 145 cells but absent on PC-3. TNF-alpha and IL-10 enhanced ELAM-1 on DU 145, but EosA 24 hr supematants failed to do so. All three cytokines, namely IL-10, IL-12 and TNF-alpha-induced ELAM-1 on PC-3 tumor cells. Although VCAM-1 was absent on DU 145 and PC-3 cells, it was expressed on DU-145 cells after exposure to EosA: tumor cell co-cultures, and was expressed on PC-3 following exposure to IL-10 and IL-12. N-cadherin and E-cadherin were both expressed on DU-145. While N-cadherin was expressed on PC-3 cells, E-cadherin was not. N-cadherin was enhanced on DU-145 and PC-3 cells following exposure to EosA co-culture and upregulated on PC-3 by IL-10 and EosA 24 hr supernatants, but decreased by IL-12. E-cadherin was up-regulated on DU 145 cells following co-culture with EosA and was induced on PC-3 by IL-10 and IL-12, but not by EosA co-culture and 24 hr supematants. In conclusion, inflammatory and non-inflammatory cytokines modulate CAM expression on Pca cells; EosA and EosA 24 hr supernatants also exerted modulatory activity of CAM expression. Most significantly, the metastasis suppressor molecule, E-cadherin was enhanced on DU 145 cells by EosA and induced on PC-3 by IL-10 and IL-12 both of which are produced by EosA. This suggests potential use of these cytokines in immunotherapeutic strategies for prostate cancer and its metastasis.