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Expression And Significance Of NF-κB/p65, P-IκBα And IκKα In Cutaneous SCC And BCC

Posted on:2008-07-19Degree:MasterType:Thesis
Country:ChinaCandidate:M M LiFull Text:PDF
GTID:2144360215460288Subject:Surgery
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Background and objectiveCutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) which are common skin malignant tumors all belong to the non-melanoma skin carcinoma (NMSC). Like other malignant tumors, their transformation is also a multistage, progressive process. Traditionally, it is regarded as a result with multimutation of genes, including such as mutation of oncogenes, inactivation of tumor suppressor genes and unbalance of apoptosis. However, once tissue cells transform into malignant cells, their bio-behaviour also change into continuous and unlimited proliferation, and finally form a tumor. In any case, development of carcinoma need signal pathway at last.Nuclear factor-kappaB (NF-κB) signal pathway play an important role in formation of carcinoma. The pathway includes inhibitor of nuclear factor kappaB kinase (IκK), inhibitor of nuclear factor kappaB (IκB), nuclear factor-kappaB (NF-κB) and so on. At rest, NF-κB combines IκB that is in an inactive form in the cytoplasm. Be stimulated by some factors, IκK is activated, which phosphorylate IκB, and then, IκB leaves from NF-κB-IκBαcomplex by the function of ubiquitination. NF-κB begin play its action such as antiapoptosis, promoting proliferation of cells, activating oncogene and so on.We screened IκKα, p-IκBα, NF-κB/p65 expression by immunohistochemistry in SCC, BCC and normal skin tissue to investigate the relationship between expression of these proteins and formation, growth of SCC and BCC.Materials and methods53 skin carcinoma tissue specimens (SCC 27, BCC 26) were obtained by surgical exision of leisions from scalp, face, back and limbs. There were 26 males and 27 famales. 20 human skin tissue samples of normal skin were from scalp, face, upper arm, abdomen and thigh of non-carcinoma patients or cosmesisors. The pathology classifies of SCC: grade I includes 21 cases, grade II and III include 6 cases. No case accepted radiotherapy, chemotherapy etc in preoperative. Immunohistochemical SP method was used in this study. The data was analysed by SPSS11.0 software package. The level of signifmant difference was a=0.05.Results1. The positive expression of IκKαwas mainly in the cytoplasm of tumor cells and parts of vascular endothelial cells in cutaneous carcinoma. 20 normal skin tissue showed 3 positive staining for IκKα. The positive rate of IκKαwas 77.80%(21/27) in SCC, 46.20%(12/26) in BCC and 15.00%(3/20) in normal skin respectively. There was significant difference between SCC (or BCC) and normal skin (P<0.05). There also was significant difference between SCC and BCC (P<0.05). The expression of IκKαin SCC was no significant relationship with pathological grade (P>0.05).2. The positive expression of p-IκBαwas localized in the cytoplasm of tumor cells. The positive rates of p-IκBαwas 70.40%(19/27) in SCC, 42.31%(11/26) in BCC respectively. 17 normal skin tissues were negative. There was significant difference between SCC(or BCC) and normal skin (P<0.05). There also was significant difference between SCC and BCC (P<0.05).3. The positive expression of NF-κB/p65 was mainly localized in the cytoplasm of tumor cells and occasionally express in nucleus of tumor cells. Within tumors, major cancer cells are positive putting colour, in diffusion being distributed in cancer organization, and few part cancer cells assume the cluster scattering in cancer organization. The positive rates of NF-κB/p65 was 74.10%(20/27) in SCC, 42.31%(11/26) in BCC respectively. 18 normal skin tissues were negative. There was significant difference between SCC (or BCC) and normal skin (P< 0.05). There also was significant difference between SCC and BCC (P<0.05). The expression of NF-κB/p65 in SCC was no significant relationship with pathological grade (P>0.05).4. Correlative analysis showed the expression of IκKαand p-IκBa had a positive relationship(P<0.05); expression of NF-κB/p65 and p-IκBαhad a positive relationship(P<0.05).Conclusions1. Comparing with the nomal skin, overexpression of NF-κB/p65, p-IκBαand IκKαin SCC, BCC suggest that the NF-kB signal transduction pathway may play an important role in carcinogenesis of SCC and BCC.2. The expression of NF-KB/p65, p-IκBαand IκKαin BCC is significantly lower than in SCC may be related to the slower growth and rare metastasis of BCC.3. The expression of p-IκBαis significantly correlated with IκKαin SCC and BCC; the expression of NF-κB/p65 is significantly correlated with p-IκBαin SCC and BCC. Above those suggest that the three factors consisting in the NF-κB signal transduction pathway induces the formation and growth of SCC and BCC by cooperating with each other.4. NF-κB/p65 may become a new target to cure SCC and BCC because it's the key point in the NF-κB signal transduction pathway.
Keywords/Search Tags:Squamous cell carcinoma (SCC), Basal cell carcinoma (BCC), NF-kB, IκBα, IκKα
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