Expression Of STAT3、p27and CyclinD1in Cutaneous Malignant Melanoma

Background and PurposeCutaneous malignant melanoma (CMM),as one of familiar malignant tumors of skin,is derived from melanocytes. It is the fastest growing skin malignant tumors. As well as other human tumors, its growth and development are very complicated process, combined action of multiple factors and multiple steps and stages. Mainly include the activation of oncogenes, reducing or disappear of the activity of tumor-suppressor genes, resulting in the changes of cell cycle, cause cancer cells to grow out of control.Signal transducers and activators of transcription3(STAT3) is an important members of signal transducers and activators (STATS) of transcriptions. Generally, STAT3resides in the cytoplasm, when upstream signaling pathways activated (such as EGFR, c-Met, il-6receptor activation, etc.), STAT3phosphorylated to form dimers or form a heterodimer with other members of the STAT family. Activated STAT3complex translocate to nucleus, the transcription of its target genes(include CyclinDl、Bcl-xL、c-myc、and VEGF,etc.)will begin. STAT3promote cancerous tissue cells by promoting the expression of cell CyclinDl and Unlimited cell proliferation.The change of the cell cycle will lead the cancer cells to grow out of control.CDKI can inhibit the compound formation cyclin and CDK, the inactivation of CDKI leads to cell proliferation.As a CDKI,p27can inhibit the activation of CyclinDl/CDK4and CyclinE/CDK2,thus made the cell cycle stagnate in G1and interfere with the cells of infinite proliferation, thus inhibiting tissue cells become cancerous. To understand the role of STAT3、p27and CyclinDl in the pathogenesis of CMM, this study tested the expression of STAT3, p27, CyclinD1in54cases CMM,22case mole skin junction,20cases normal skin, and analyze the correlation of the three factors.Materials and methods54case CMM and22case mole skin junction were selected from the department of pathology in the first affiliated hospital of Zhengzhou University which archived from September2008to May2012. All patients had no therapy before,for example, freezing,laser, biotherapy and so on.They had no skin disorder connective tissue disease, immune disorders and other important organs diseases.20cases of normal skin which came from full thick skin grafts of plastic surgery were chosen as control groups.The SP immunohistochemical technique was used to detect the expression of STAT3, p27, CyclinD1in the development of CMM. The statistics data were processed by SPSS17.0, using Chi. square test and correlation analysis. The test standard is0.05and the standard of X2division is0.0167.Results1. STAT3expressed mainly on the cytoplasm of melanoma cells. There was a high expression in CMM, their positive expression is77.8%(42/54). There were low expression in mole skin junction or normal skin, their positive expression were45.5%(10/22、35.0%(7/20). There was a statistical significance between the CMM and mole skin junction or normal skin(P<0.0167).There is no statistical significance between mole skin junction and normal skin(p>0.0167).2. p27expressed mainly on the nucleus of melanoma cells. There was a low expression in CMM, their positive expression is16.7%(9/54). There were low expression in mole skin junction or normal skin, their positive expression were86.4%(19/22)、95.0%(19/20).There was a statistical significance between the CMM and mole skin junction or normal skin (p<0.0167). There is no statistical significance between mole skin junction and normal skin (p>0.0167).3. CyclinDl expressed mainly on the nucleus of melanoma cells. There was a high expression in CMM, their positive expression is81.5%(44/54). There were low expression in mole skin junction or normal skin, their positive expression were45.0%(10/22、30.0%(6/20). There was a statistical significance between the CMM and mole skin junction or normal skin(p<0.0167).There is no statistical significance between mole skin junction and normal skin(p>0.0167).4. The correlation analysis showed that there was a significant negative correlation between STAT3and p27(r=-0.478,p<0.05). There was a significant negative correlation between CyclinDl and p27(r=-0.426,p<0.05). There was a significant positive correlation between STAT3and CyclinDl (r=0.663,p<0.05).Conclusion1. Both the expressions of STAT3protein and CyclinD1protein in CMM are higher than in mole skin junction and normal skin. Their high expression may promote the growth of the melanocytes, thus cause the happening of the CMM. Prompt that the two factors may play a positive role in the occurrence of the CMM.2. The expression of p27in CMM is lower than in mole skin junction and normal skin. Its low expression may promote the proliferation of the melanocytes, thus cause the happening of the CMM. P27might play a tumor suppressor role in CMM for their low expressions.3. The constitutive activation of STAT3signal transduction pathways eventually promote cell proliferation, CyclinD1is its an important downstream factors, and its protein expression in the CMM can promote the operation of cell cycle to participate in the occurrence and development of CMM.4.STAT3、p27、CyclinD1may be new targets for cancer therapy, and provide the theory basis of STAT3inhibitors used in the treatment of CMM.