Expression Of PRAME In Cutaneous Malignant Melanoma And Its Clinical Significance

Background and ObjectivesMalignant melanoma(MM)is a tumor that originates from the melanocytes of the neural crest.It often occurs in the skin,mucous membranes,lymph nodes,etc.It is of extreme malignancy and prone to metastasize by blood,lymphatic system,and even to distant organs in an early stage.Cutaneous malignant melanoma(CMM)is the most malignant tumor among skin tumors,accounting for more than 75%of deaths by skin cancer.The incidence has rapidly increased globally in recent years.There are more than 8,000 new cutaneous melanoma patients in China each year,so early and accurate diagnosis of the disease is of vital importance to improve the prognosis.Histopathological examination is the gold standard for the diagnosis of malignant melanoma.The exploration and discovery of new biomarkers will help diagnose the disease more accurately,and may help develop new targeted therapies or immunotherapy drugs.PRAME(Preferentially expressed antigen in melanoma)gene plays an important role in the occurrence and development of a variety of malignant tumors and is correlated with the skin melanoma of human.Some scholars abroad have studied the expression and significance of PRAME in cutaneous melanoma in Caucasian.However,there was no domestic research on that aspect.This study was based on the patients of cutaneous melanoma among Chinese Han population,and explored the expression and its clinical significance of PRAME in cutaneous melanoma tissues.MethodsThe expressions of PRAME,S100,and MART-1(melanoma antigen recognized by T cells 1)in 43 cases of cutaneous melanoma tissue and the expression of PRAME in 15 cases of melanocytic nevi tissue were detected by immunohistochemistry(IHC)SP staining.Chi-square test and Fisher exact test were used to analyze statistically the experimental data by Graphpad Prism 8.0 and SPSS 21.0,showing by percentage(%)or numbers of case(n),and P<0.05 was considered statistically significant.Results1.The positive expression rate of PRAME in human cutaneous melanoma tissue was higher than that in skin melanocyte nevi,and the difference is statistically significant(P<0.05).Among the 43 cases of human tissues of cutaneous malignant melanoma in this experiment,PRAME was diffusely expressed in 18 cases,positively expressed in 37 cases,and negatively expressed in 6 cases.Among the 15 cases of human tissues of cutaneous melanocytic nevi,PRAME was positively expressed in 1 case and negatively expressed in 14 cases.The Yates corrected chi-square value was χ2=27.60,P<0.0001,and the difference in expression of PRAME in human cutaneous melanoma and human cutaneous melanocyte nevi was statistically significant(P<0.05).2.The positive expression rate of PRAME in human cutaneous melanoma tissue was not significantly different from that of S100 and MART-1(P>0.05).Among the 43 cases of human cutaneous malignant melanoma tissues in this experiment,11 cases in S100 group showed diffuse expression,41 cases showed positive expression,and 2 cases showed negative expression.The positive rate was 95.35%;MART-1 was diffusely expressed in 17 cases,positively expressed in 35 cases,negatively expressed in 8 cases.The positive rate was 81.40%.The comparison among three groups:x2=3.996,P=0.136;the comparison between PRAME and S100:χ2=1.240,P=0.265;the comparison between PRAME and MART-1:χ2=0.085,P=0.770;the comparison between S100 and MART-1:χ2=2.829,P=0.093.P were all greater than 0.05,so there was no statistically significant difference in the positive rates of the three biomarkers(P>0.05).3.The positive expression rate of PRAME in human cutaneous melanoma tissue was not statistically significant in different ages,genders,or Clark grades(P>0.05).There were 43 patients in the cutaneous melanoma group,17 of whom were younger than 60 years old,of which 14 were positive in PRAME IHC and 3 were negative;there were 26 patients in the 60 years and older group,of whom 23 were positive and 3 were negative in PRAME IHC.To compare the difference in the positive rate of PRAME between the two groups,the Yates corrected chi-square value was χ2=0.013,P=0.908,the difference was not statistically significant(P>0.05).Among the 43 patients,18 were males,of whom 16 were positive and 2 were negative in PRAME IHC;there were 25 females,of whom 21 were positive and 4 were negative in PRAME IHC.To compare the difference in the positive rate of PRAME between the two groups,the Yates corrected chi-square value was χ2=0.000,P=0.992,the difference was not statistically significant(P>0.05).Among the 43 patients,there were 17 patients at Clark I,15 of whom were positive for PRAME and 2 were negative;9 patients were at Clark Ⅱ,of whom 7 were positive for PRAME,and 2 were negative;10 patients were at Clark Ⅲ,of whom 9 were positive for PRAME and 1 was negative;5 patients were at Clark IV,of whom 4 were positive for PRAME and 1 was negative;2 persons were at Clark V level and were wholly positive for PRAME.Fisher exact test was used for comparison between the groups,χ2=1.683,P=0.859,the difference was not statistically significant(P>0.05).Conclusions1.PRAME can be used as a biomarker for the diagnosis of cutaneous malignant melanoma.2.PRAME is a valuable biomarker for the distinction of cutaneous malignant melanoma from melanocytic nevi.3.For the patients suffering from CMM whose pathological tissue are positive for PRAME,it may help to improve the prognosis through PRAME-targeted therapy or immunotherapy.