[Expression of COX-2 and MMP-9 in cervical carcinoma and their clinical significance].

OBJECTIVE: To investigate the expressions of COX-2 and MMP-9 in cervical carcinoma and their clinical significance. METHODS: Immunohistochemical SP method was used to detect the expressions of COX-2 and MMP-9 in 72 cases of invasive carcinoma of cervix (ICC) and 16 cases of normal cervical epithelium remote from tumor (NCE), and the relationship between the expressions of COX-2 and MMP-9 in ICC and some factors relating to clinical pathology of cervical carcinoma such as histopathological grading, lymph node metastasis, stroma involvement and FIGO staging were analyzed statistically. RESULTS: The rates of positive expression of COX-2 and MMP-9 in ICC were significantly higher than those in NCE. COX-2: 88.9% in group ICC and 12.5% in group NCE, P = 0.000. MMP-9: 94.4% in group ICC and 43.8% in group NCE, P = 0.000. The expression of COX-2 was positively correlated with lymph node metastasis and stroma involvement (r = 0.296, P = 0.012 in group ICC and r = 0.257, P = 0.029 in group NCE, respectively). The expression of MMP-9 was positively correlated with FIGO staging (r = 0.329, P = 0.005) and histopathological grading (r = 0.351, P = 0.003). The expression of COX-2 was positively correlated with the expression of MMP-9 in ICC (r = 0.297, P = 0.011). CONCLUSION: The overexpressions of COX-2 and MMP-9 are closely related to the invasion and growth of cervical carcinoma. The tissue with overexpression of COX-2 has strong invasion ability. COX-2 and MMP-9 have synergistic effect on proliferation, invasion and metastasis of cancer cells. Detecting the expression of both COX-2 and MMP-9 may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.

[Expression and mutation of Fas-associated death domain (FADD) gene in non-small cell lung cancer].

BACKGROUND & OBJECTIVE: Abnormal expression of Fas-associated death domain (FADD) protein, an important adapter in cell apoptosis signal conduction, may closely relate with tumorigenesis. This study was to detect expression and mutation of FADD gene in non-small cell lung cancer (NSCLC), evaluate its effect on development of NSCLC, and explore the mechanism. METHODS: Polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) was used to detect FADD gene mutation in 62 specimens of NSCLC tissues and 13 specimens of adjacent non-cancerous lung tissues. Immunohistochemistry was used to detect its protein expression. In situ hybridization (ISH) was used to detect FADD mRNA expression in 30 of the 62 specimens of NSCLC tissues. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick labeling (TUNEL) was used to detect apoptotic cells in NSCLC tissues. RESULTS: Of the 62 specimens of NSCLC tissues, 4 cases of stage N2 showed FADD gene mutation. Positive rate of FADD protein in NSCLC tissues was 80.6% (50/62), its protein level positively correlated with differentiation of NSCLC (rs=0.411, P<0.01). Protein level of FADD in NSCLC tissue was significantly higher than that in non-cancerous tissue (P<0.05). Positive rate of FADD mRNA in NSCLC tissue was 80.0%, its concordant rate with positive rate of FADD protein was 88.6% (P>0.05). Apoptotic cells were observed in all specimens of NSCLC, apoptosis indexes of the 4 cases with FADD gene mutation were lower than the mean level, although they showed positive expression of FADD protein. Protein level of FADD was positively related with cell apoptosis of NSCLC (rs=0.599, P<0.001). CONCLUSIONS: FADD gene mutation exists in NSCLC, its mutation and abnormal expression might play a crucial role in carcinogenesis of NSCLC. Protein level of FADD closely correlates with cell apoptosis of NSCLC.

[Expression of apoptosis and proliferation related genes in carcinogenesis of lung squamous cell carcinoma in rats].

BACKGROUND & OBJECTIVE: The activation of caspase-3 protein, located the downstream of apoptosis, is the key of cell apoptosis signal conduction. Caspase-3 is the most important performer in accelerating apoptosis in the caspase family. Much progress has been achieved in the study of caspase-3 and human non-small cell lung cancer. This study was designed to investigate the effect of cellular proliferation and apoptosis related genes caspase-3 and proliferating cell nuclear antigen (PCNA), and to seek whether they could be chosen as molecular biology markers for lung cancer. METHODS: 3-Methylcholanthrene (MCA) and diethyinitrosamine (DEN) were used to induce lung squamous cell carcinoma by intra-left lobar-bronchial instillation in 50 Wistar rats. The other 10 rats instilled with iodized oil were regarded as control group. The expression of caspase-3 and PCNA were evaluated by SP immunohistochemistry during carcinogenesis. TUNEL(TDT-mediated dUTP nick end labeling) method was used to examine apoptotic cells. RESULTS: For the rat bronchial epithelium cells in control group, precancerous lesions, and lung squamous cell carcinoma, positive coefficient values of caspase-3 protein were 3.10+/-0.99, 2.25+/-1.13, and 1.38+/-0.95 on average, respectively; the means of PCNA-labeling index (PCNA-LI)were 14.10+/-5.02, 28.13+/-8.72, and 41.88+/-14.24, respectively; the means of apoptotic index(AI) were 0.60+/-0.52, 2.06+/-0.85, and 2.26+/-1.14, respectively.Significant differences in caspase-3 protein expression were observed between bronchial epithelium in control group and lung squamous cell carcinoma (P< 0.01). Caspase-3 expression was showed stronger in precancerous lesions than that in lung cancer (P< 0.05). Low proliferation index and low AI were detected in rat bronchial epithelium region in control group,which were significant differences in precancerous lesions and lung cancer, respectively (P< 0.01). In 34 rats with lung squamous cell carcinoma, there was negative relationship between caspase-3 and PCNA-LI (r=-0.7306, P< 0.01), so did it in AI and PCNA-LI(r=-0.8127,P< 0.01), but there was no relationship between caspase-3 expression and AI(P >0.05). CONCLUSION: Loss of caspase-3 expression may be associated with the development of lung squamous cell carcinoma in Wistar rats, but it is not associated with AI. PCNA-LI is an important marker for malignant progression of lung cancer.