Expression Of MITF, S-100 Protein And HMB45 In Patients With MM And Pigmented Nevus

Originated from melanocyte of neural crest,malignant melanoma(MM) progresses rapidly,has a relatively higher grade of malignancy,and results in a high death rate.On the other hand,the incidence of MM continued to increase recently.Thus,early detect and correct diagnosis of MM is of great importance.Histopathology of MM varies a lot.Particularly,it is difficult to distinguish spindle-cell MM and fibrogenic MM from malignant tumor originated from mesenchymal tissue.Therefore,immunostaining of MM is of great significance.Markers to melanocytes employed frequently nowadays are S-100 protein and HMB45.S-100 protein,a subgroup of acid Ca²⁺-binding protein of low molecular weight,is mainly found in cytoplasm of CNS glial cells.Being a Ca²⁺-binding protein,S-100 plays a role in cell development,figure and function,as well as intracellular and intercellular signal transduction.Since melanocytes originated from neural crest,they can also be positively stained by S-100.Therefore,S-100 immunostaining is a sensitive marker of MM and pigmental nevus.Besides melanocytes,S-100 is also expressed in glial cells,Schwann cells,muscle cells,lipocytes and fibroblasts.Thus,tumor related to these cells can also be stained by S-100. Being a sensitive but non-special marker,clinical application of S-100 is restricted.HMB45 antibody stains a 10KDa cytoplasmic glycoprotein thought to be part of the premelanosome complex.Normal adult melanocytes can not be stained by HMB45,while melanocytes of both primary and metastasis MM can be labelled with exclusions of spindle-cell MM and fibrogenic MM.Thus, HMB45 is marker of high specificity but low sensitivity.MITF,a nuclear transcription factor located in nuclear of melanocyte,plays a crucial role in the development and function of melanocyte.Lies at the heart of multi-signal transduction pathways related to differentiation of melanocytes,MITF regulates morphology,differentiation and survival of melanocyte-originated cells,including primary melanocytes,melanocytes and MM cells.Stain model of MITF is different from other markers.For one thing,MITF stains nuclears but not cytoplasm;Secondly,necrosis tumor tissue can not be labelled. Therefore,MITF is a hotspot of worldwide researchers.To study the expression of MITF,S-100 and HMB45 in MM and pigmented nevus,specimens of 32 MM,2 Spitz nevus,4 pigmental nevus and 2 blue nevus were stained by S-100 protein,HMB45 antigen and MITF-Ncl.Out of 32 MM stained by S-100,1 was negative,13 were + positive,7 were ++ positive,11 were +++ positive.Positive rate was 96.7%.Besides MM cells,normal melanocytes,myo-epithelial cells and some fibroblasts were also positively stained.Four pigmental nevus,2 blue nevus and 2 spitz nevus were also positive for S-100.As to results of HMB45 staining for 32 MM,6 were negative,16 were + positive,3 ++ positive and 7 +++ positive.Positive rate was 81.2%.Among the 6 negative MM,2 cases were primary MM, another 2 cases were lymph node metastasis,still 2 were spindle cell MM. When comes to other diseases stained by HMB45,1 junctional-nevus and 2 spitz nevus were positive while other 3 pigmental nevus and 2 blue nevus were negative.Normal melanocytes did not express HMB45.Compared to S-100 protein,positive rate of HMB45 staining was statistically different.As for results for MITF staining,only one case out of 32 MM was negative,while other 31 cases were positive.Positive rate was 96.7%.Four pigmental nevus,2 blue nevus and 2 spitz nevus were all positive.Positive reaction was detected exclusively in melanocytes,nevus cells and MM cells.Metastasis MM was also positively stained by MITF.Statistical analysis showed that sensitivity of MITF was higher than HMB45.In short,results revealed that positive rate of MM and pigmented disorders was high after stained by S-100 protein(96.7%and 100% repectively),yet the specificity was relatively low.Fibroblasts,myo-epithelial cells,histocytes and Langerhans cells in normal skin also positively expressed S-100.On the contrary,specificity of HMB45 was high,only MM cells and junction nevus cells were stained,whereas melanocytes in normal tissue and benign intradermal nevus can not be labelled.Expressed in nuclears of melanocytes,MM cells and nevus cells,MITF showed both high specificity and high sensitivity.MITF was also well expressed in metastasis MM and spindle-cell MM.It can be concluded that MITF is a specific marker for diagnosis and differential diagnosis of MM.