Study Of C-erbB-2,P16,nm23-H1 In Non-melanoma Skin Cancer

Malignant tumor transformation is a multistage, progressive process. Present studies indicate that multiple molecular changes, such as those found in oncogenes, tumor suppressor genes , tumor-metastatic suppressor genes and apoptosis. Non-melanoma skin cancer (NMSC), included basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is one of the malignant diseases and a serious threat to human health. The causes of NMSC are complicated because many genes mutation might contribute to its development and touch on external causes. Furthermore, the molecular mechanisms that cause mutation accumulation and development of carcinomas are not yet clear.Oncogene c-erbB-2 is one of epidermal growth factor genes and it's product may come into being standing stimulating-signal, then transduction processes can be initiated. Further, it may determine the potency and diversity of intracellular signals leading to malignant transformation and proliferation of malignant tissue; Tumor suppressor gene P16, a recognized tumor suppressor, induces G1 cell-cycle arrest by binding to CDK4, and inhibiting its ability to interact with cyclinD and stimulate passage through the G1/S phase of the cell cycle. In addition, P16 controls cell-cycle and induces apoptosis and participate in tumorigenesis;Tumor-metastatic suppressor gene nm23-H1 is a heterodimeric protein that acts as a nucleoside diphosphate (NDP) kinase. The products of these genes encode polypeptide chains of the nucleoside diphosphate kinase. NDP kinases are involved in the synthesis of nucleoside triphosphates, and the nm23-H1 protein may act in the regulation of signal transduction by complexing with G proteins, causingactivation/inactivation of developmental pathways and participate in tumorigenesis and metastatic. Whereas, the relationship of c-erbB-2, P16 and nm23-Hl in NMSC have received little attention in domestic and foreign literatures. Moreover, the views are not agree with each other. In the current study, the expression of c-erbB-2, P16 and nm23-Hl protein in 42 samples of NMSC were analyzed and investigated how their expression relates to NMSC using an immunohistochemical method. It will provide theoretic basis for tumorigenesis mechanism and gene therapy.Materials and methods:The samples of NMSC were obtained from 42 patients who were underwent surgery; carcinoma tissue were collected from scalp, face, back and perineum. There were 27 males and 15 females. The age of patients from 36 to 91years old (mean: 61.5 years old). To elucidate the involvement of c-erbB-2, P16 and nm23-Hlin NMSC, expression of the protein by immunohistochemistry using monoclonal antibodies to c-erbB-2^ P16 and nm23-Hl were examined. Statistical analysis was performed by the SPSS 10.0 software package. Values were calculated as means±standard deviation (x +s). Differences among groups were analyzed by using analysis of variance, the Chi-squared test and Q test. All of the P values resulted from two-sided statistical test. Statistically significant level was considered as "alpha equals 0.05"( a = 0.05).Results:1. Expression of c-erbB-2 protein: c-erbB-2 immunostaining was detectable in cytoplasm or/and membrane of basal cell > glandular cell and squamous cell. The positive immunostaining rates of c-erbB-2 are 47.4%(9/19) in BCC. 56.5%(13/23) in SCC and 13.3%(2/15) in normal skin, and respectively. Comparing the staining rate and intensity of NMSC and normal skin respectively, there were significant differences (P< 0.05).2. Expression of P16 protein: P16 immunostaining was detectable in nucleus or/and cytoplasm of basal cell and squamous cell. The positive immunostaining rates ofP16 are 63.2%(12/19) in BCC, 52.2%(12/23) in SCC and 100%(15/15) in normal skin respectively. Comparing the staining rate and intensity of NMSC and normal skin respectively, there were significant differences (P< 0.05).3. Expression of nm23-Hl protein: nm23-Hl immunostaining was detectable in cytoplasm or/and nucleus of basal celk glandular cell and squamous cell. The positive immunostaining rates of nm23-Hl 68.4%(13/19) in BCC> 47.8%(ll/23) SCC and 100%(15/15) normal skin respectively. Comparing the staining rate and intensity of NMSC and normal skin respectively, there were significant differences (P< 0.05).4. In the 42 cases of NMSC, there were 11 cases with positive staining of c-erbB-2 and negative staining of PI6, 13 cases with negative staining of c-erbB-2 and positive staining of P16, 11 cases with positive staining of both c-erbB-2 and P16, and 7 cases with negative staining of both c-erbB-2 and P16. There was no correlationship between the expression of c-erbB-2 and that of P16 (P> 0.05).5. In the 42 cases of NMSC, there were 13 cases with positive staining of c-erbB-2 and negative staining of nm23-Hl, 15 cases with negative staining of c-erbB-2 and positive staining of nm23-Hl, 9 cases with positive staining of both c-erbB-2 and nm23-Hl, and 5 cases with negative staining of both c-erbB-2 and nm23-Hl. There was negative correlationship between the expression of c-erbB-2 and that of nm23-Hl (rs = 0.325, P< 0.05).6. In the 42 cases NMSC, there were 6 cases with positive staining of P16 and negative staining of nm23-Hl, 6 cases with negative staining of P16 and positive staining of nm23-Hl, 18 cases with positive staining of both P16 and nm23-Hl, and 12 cases with negative staining of both P16 and nm23-Hl. There was positive correlationship between the expression of P16 and that of nm23-Hl (rs = 0.385, P< 0.05).Conclusions:l.In NMSC, overexpression of c-erbB-2 indicated that there was positive correlationship, between c-erbB-2 and the degree of malignant progress, tumorinvasiveness, biological behavior and prognosis.2. In NMSC, underexpression of P16 and nm23-Hl suggested that there was negative correlationship, between PI6, nm23-Hl overexpression and the degree of malignant progress, tumor invasiveness, biological behavior and prognosis.3. Positive correlation between P16 and nm23-Hl indicated P16 might increase nm23-Hl during the progression of NMSC.4. Overexpression of P16 and nm23-Hl in BCC indicated which correlated with lower malignance and non-metastatic of biological behavior.