Altered expression of the DNA mismatch repair proteins hMLH1 and hMSH2 in cutaneous dysplastic nevi and malignant melanoma.
Molecular alterations in the mismatch repair system suggest that this mechanism may be important in the evolution of cutaneous melanoma. Our current study evaluated the expression of two mismatch repair proteins, hMLH1 and hMSH2, in dysplastic nevi (DN) and cutaneous melanoma (CM). Immunohistochemical staining of these proteins was performed on 55 CM and 30 DN specimens. The staining results were divided into three groups: negative, partially positive and strongly positive. Normal adjacent skin cells served as an internal control for positive immunostaining. Altered immunoreactivity of one of the proteins was found in four (13.4%) DN and seven (12.7%) CM. Lack of staining for hMLH1 was observed in two (6.7%) cases of DN and five (9.1%) cases of CM; staining for hMSH2 was absent in two (6.7%) of the DN and two (3.6%) of the CM specimens. Partially positive staining was found in 33.3% and 53.3% for hMLH1 and hMSH2, respectively, in DN, and in 54.5% and 69.1%, respectively, in CMM. Our study shows that complete or partial loss of MMR protein expression occurs in a subset of both DN and CM and may represent a distinct pathway in the development of some DN and CM.
Shpitz
B
B
Department of Surgery, Laboratory of Oncogenetics, Sapir Medical Center, Meir General Hospital, Kfar Sava, Israel. shpitzca@post.tau.ac.lt
Klein
E
E
Malinger
P
P
Osmolovsky
G
G
Gochberg
S
S
Bomstein
Y
Y
Bernheim
J
J
D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch / Q000235:genetics; D002352:Carrier Proteins; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004416:Dysplastic Nevus Syndrome / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein