The Expressions Of KLF6and Ki67Proteins In Patients With Cutaneous Malignant Melanoma

BackgroundMalignant melanoma originates from naevus cells and melanocytes; it isassociated with poor prognosis and high mortality due to its high degree ofmalignancy, early blood and lymphatic metastasis and resistance to chemotherapy andradiotherapy.Except for the cases of the early detection and treatmented, cutaneousmalignant melanoma (CMM) is still a progression rapidly and treatment resistance ofthe malignant tumor,the early discovery and resection of operation is still themainstream therapy perspectives. But for the incidence of invasion, metastasis oroccur after operation,the patient’s prognosis and survival time depends on themselves’condition,biological marker types and tumor characteristics. However,the prognosisalmostly depends on limited clinical data and analysis of histological characteristicsnowdays, while there is some reference value to the overall prognosis of thisdisease,there is no direct impact on the personalized treatment for MM moremeaningful.In recent years, using molecular markers of tumor tissue to predict the prognosisof the study is being recognized and valued by the people, and has madepreliminary findings that it is identified initially the most prognostic value ofmolecular markers of patients with malignant melanoma,which are MCAM/MUC18,MMP-2and Ki67, PCNA and p16/INK4A. KLF6gene, encoding Krüppel-like factor6(Krüppel-like factor6, KLF6), is anuclear transcription factor,which located on chromosome10P15chromosomeregion,is the second tumor suppressor gene found in this region,the importantfunctions is regulate cell growth,differentiation and proliferation,acceleratingapoptosis and participate in the regulation of cellular senescence.As a tumorsuppressor gene, KLF6gene functional inactivation is confirmed in astrocytomas,prostate cancer, stomach cancer, liver cancer and colon cancer, but its expression inmalignant melanoma tissues and prognostic value of literature is rarely.At present,foreign related malignant melanoma KLF-6and Ki67expression studies is only a fewreported, and our country has not been reported.In this paper, usingimmunohistochemical SP method for cutaneous malignant melanoma and intradermalnevus tissue expression of KLF-6and Ki67is conducted preliminary studies, toinvestigate malignant melanoma pathogenesis and its role in cell proliferation,formalignant melanoma prevention, prognosis analysis and the choice of therapeutictargets provide the basis.ObjectiveThe aims of this study is to investigate the expression of Kruppel-like factor6(KLF6) and Ki-67in the patients with cutaneous malignant melanoma or nevocyticnevus,and explores its role and significance in the pathogenesis of cutaneousmalignant melanoma and tumor cell proliferation.Materials and Methods1. The tissue samples of28primary cutaneous malignant melanoma(PCMM),17metastatic cutaneous malignant melanoma(MCMM) and30nevocytic nevus werecollected. All specimens were from, our hospital dermatology clinic, inpatients ordepartment of plastic surgery after confirmation and surgery during January,2008toJuly,2013. Inclusion criteria:①All patients recruited had been confirmed by skin biopsy in our hospital;②All patients recruited have no the medical history of othermalignancy;③Any form of chemotherapy and radiation therapy were not given atleast4weeks before drawing materials and any form of topical agent were also notgiven within2weeks, otherwise, the patient was the first visit;④All patients recruitedhad been told the objective, methods and keeping their condition secret and thewritten permission were asked.2. The tissue was stained by HE conventionally, and then, the expression of KLF6andKi-67in the tissues of28primary cutaneous malignant melanoma,17metastaticcutaneous malignant melanoma and30nevocytic nevus were detected viaimmunohistochemical SP method.3. Statistics analysis: All the data of this test were analyzed by the SPSS17.0statistical software and the measurement data are expressed withX±S, The overalldifference were analysed using Kruskal-Wallis rank test and the pairwise comparisonbetween data are performed by the Bonferroni method. The overall inspection level isα=0.05.Results1.The expression of KLF6in tissues of cutaneous malignant melanoma and nevocyticnevus.The positive rate of KLF6stained in the skin tissues of primary cutaneousmalignant melanoma, metastatic cutaneous malignant melanoma and nevocytic nevusare21.43%、17.64%、100%.The positive expression in the cytoplasm and nucleus isyellowish and brown fine particles or homogeneous. Furthermore, the expressionlevel of KLF6in cutaneous malignant melanoma is mostly lower, which is mostlyhigher in nevocytic nevus. Compared with cutaneous malignant melanomaintradermal nevi group, the difference is statistically significant (P<0.05). PCMMgroup compared with MCMM group, the difference is not statistically significant (P>0.05). The average rate of positive cells compared with cutaneous malignant melanoma intradermal nevus group difference is statistically significant (P<0.05), butPCMM group compared with MCMM group, the difference is not statisticallysignificant (P>0.05).2. The expression of Ki-67in tissues of cutaneous malignant melanoma and nevocyticnevus.The positive rate of Ki-67stained in the skin tissues of primary cutaneousmalignant melanoma, metastatic cutaneous malignant melanoma and nevocytic nevusare100%、100%、6.67%.The positive expression in the nucleus is brownparticles.Ki-67protein is highly expressed in cutaneous malignant melanoma group,low or no expression in intradermal nevi group, cutaneous malignant melanoma groupand intradermal nevi group, the difference is statistically significant (P<0.01).PCMM group and MCMM group, the difference is not statistically significant (P>0.05). The average rate of positive cells compared with cutaneous malignantmelanoma intradermal nevus group difference is statistically significant (P <0.05),PCMM group compared with MCMM group, the difference is not statisticallysignificant (P>0.05).3.The correlation between the3KLF6and Ki-67protein expressionThe expression level of KLF6in cutaneous malignant melanoma is mostly lower, which ismostly higher in nevocytic nevus.Ki-67protein expression is contrast,and shows a significantnegative correlation (r=-0.368, P <0.01).ConclusionThe positive rate of KLF6protein in cutaneous malignant melanoma tissues decreasessignificantly compared with intradermal nevus tissue,there is no significant difference between theprimary CMM and metastatic CMM; KLF6protein and Ki-67protein expression negativelycorrelated;which suggestes that the lower positive rate of KLF6protein may be relevant to Theformation of cutaneous malignant melanoma.