title: Differential expression of proliferation- and apoptosis-related markers in lentigo maligna and solar keratosis keratinocytes.
abstract: Keratinocytes influence the number, morphology, and proliferation of melanocytes. An interference in the melanocyte-keratinocyte relationship may contribute to melanoma development. This study examined the expression of apoptotic and proliferative markers in keratinocytes in lentigo maligna to characterize the epidermis permissive to these lesions. Formalin-fixed and paraffin-embedded tissues from 25 samples of lentigo maligna, 20 samples of solar keratoses, and 5 samples each of normal sun-exposed and non-sun-exposed skin (controls) were immunostained with antibodies directed against the proapoptotic markers bax and p53, the antiapoptotic marker bcl-2, and the proliferation marker ki-67. Eight percent of the lentigo maligna samples were positive for keratinocyte expression of bcl-2, 24% were positive for p53, and 76% were positive for bax; respective findings for solar keratoses were 35%, 85%, and 90%. Comparison with normal sun-exposed skin yielded lower rates of keratinocyte proliferation in 56% of the lentigo maligna samples, similar rates in 36%, and higher rates in 8%; for solar keratoses, proliferation was higher than controls in 60% of samples, similar in 35%, and lower in 5%. All these differences were statistically significant. These findings indicate that there are variable patterns of epidermal reaction to chronic sun exposure. The epidermis in lentigo maligna shows overall low proliferation and an apparently low apoptotic tendency. The dysfunctional epidermis may be permissive to aberrant melanocyte proliferation in the early stages of melanoma development.
authors.affiliation: Department of Pathology, Rabin Medical Center, Beilinson Campus of the Sackler School of Medicine, Tel Aviv University, Petah Tivka, Israel.
authors.forename: Meora
authors.initials: M
authors.lastname: Feinmesser
authors.forename: Cohava
authors.initials: C
authors.lastname: Tsabari
authors.forename: Suzana
authors.initials: S
authors.lastname: Fichman
authors.forename: Emmilia
authors.initials: E
authors.lastname: Hodak
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Sulkes
authors.forename: Elimelech
authors.initials: E
authors.lastname: Okon
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers / Q000032:analysis; D002455:Cell Division; D006801:Humans; D018327:Hutchinson's Melanotic Freckle / Q000378:metabolism* / Q000473:pathology; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D007642:Keratosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D011230:Precancerous Conditions / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D013472:Sunlight / Q000009:adverse effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D015415:Biomarkers; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein