Relationship of Ras,MAPK and CyclinD1 Pathway in Carcinogenesis of Cutaneous Pathologic Scar

Abstract

Objective To detect the function of Ras/Raf/MAPK pathway and the downstream target gene CyclinD1 in the carcinogenesis of cutaneous pathologic scar.Methods(1) We adopted immunofluorescence dual staining for K-ras,H-ras and N-ras in the pathologic scar and carcinoma of scar,respectively,and observed under laser confocal microscopy;(2) Immunohistochemistry(IHC) for MAPK and CyclinD1 were used for normal skin,pathologic scar and carcinoma of scar,respectively;(3) In situ hybridization(ISH) was used for mRNA detection of MAPK and CyclinD1;(4) The 12th and 13th codon mutations of K-ras,H-ras and N-ras were detected by genetic sequencing.Results(1) The dual labeling of immunofluorescence of K-ras,H-ras and N-ras showed weak positive in pathologic scar,while the carcinoma of scar were strong positive.(2) ISH for mRNA of MAPK and CyclinD1 showed negative or weak positive in the normal epidermis and pathological scar,but strong positive in the carcinoma of scar.The expression level(positive area) and intensity(average optical density) between the carcinoma group and normal skin group or pathologic scar group were statistical different(P0.01);but without statistical difference between normal skin group and pathologic scar group(P0.05).(3) Genetic sequencing did not show mutation on the 12th or 13th codon.Conclusion(1) Ras,MAPK and CyclinD1 were not early signals for carcinogenesis of pathologic scar.(2) The 12th or 13th codon mutation of K-ras,H-ras and N-ras was not related with the carcinogenesis of pathologic scar.