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.

Correlation between Bcl‐2 and Bax in atrophic and hypertrophic type of actinic keratosis

“…and one performed by Feinmesser et al 46 . Feinmesser analysed Bcl‐2 expression in 20 AK and revealed positivity in only 35% of cases 46 . In our study, all investigated AK showed Bcl‐2 expression but the majority was weakly positive, and only 41.7% of investigated AK had stronger immunoreaction than unaffected perilesional skin that is consistent with results in the literature 36,37,46 .…”

Contiguous lesions in lentigo maligna

“…20 Mutations in the keratinocyte p53 molecule, because of the effects of chronic UV exposure, causes a cascade of events leading to an epidermis that is fertile ground for mutated junctional melanocytes that could evolve into malignant melanoma in situ. 19 Although we view the presence of an associated solar lentigo to be primarily a diagnostic pitfall in the diagnosis of LM, the possibility that they could represent a precursor lesion deserves further study. Pigmented lesions suspicious for LM are typically mottled rather than homogeneous.…”

“…[17][18][19] Interference in keratinocyte and melanocyte contact and communication via the adhesion molecule Mel-CAM has been found to contribute to melanoma development. 20 Mutations in the keratinocyte p53 molecule, because of the effects of chronic UV exposure, causes a cascade of events leading to an epidermis that is fertile ground for mutated junctional melanocytes that could evolve into malignant melanoma in situ.…”

Expression of apoptotic and cell proliferation regulatory proteins in actinic cheilitis

“…It has been recognized that UV radiation induces the formation of sunburn cells, which are apoptotic cells with increased expression of proapoptotic proteins, such as p53 and bax, and decreased expression of anti‐apoptotic proteins such as bcl‐2. Ki‐67 expression is also increased in sunburn cells (22–27).…”