Our findings also show that progression from naevi to malignant melanoma may be driven by the acquisition of additional genetic alterations, including CDKN2A homozygous deletions.
This article highlights the importance of considering CDKN2A mutations in patients with dysplastic naevi, melanoma and multiple nerve sheath tumours, specifically those with histological features of both neurofibromas and schwannomas.
The results suggest that strong p16 expression in the villous mesenchyme may be responsible in part of the morbidity of the moles, and the key of cancer progression in the choriocarcinomas would be a fast cell-cycle turnover.
All the childhood melanoma cases were associated with loss of p16 without any correlation with their Breslow thickness whereas all the Spitz nevi and benign melanocytic nevi had strong positive nuclear and cytoplasmic expression of p16 staining.
Also, inactivation of the p16 gene (CDKN2A) was absent in naevi and present at steadily increasing rates moving from primary melanomas (7% early lesions to 17% advanced lesions) to melanoma metastases (62%) (P=0.004).
Here we show that HDAC1 is prominently detected in p16(INK4a)-positive, senescent intradermal melanocytic nevi but not in proliferating, recurrent nevus cells that localize to the epidermal/dermal junction.
Penetrance of CDKN2A gene was found to be significantly influenced by host factors (nevus phenotypes and sunburn) on one hand and by variants of MC1R gene (RHC variants consistently associated with red hair and fair skin) on the other hand.
We determined mutations in the BRAF, N-ras, and CDKN2A genes in 27 histologically diverse melanocytic nevi and corresponding surrounding tissues from 17 individuals.
Five markers in the CDKN2A region were genotyped in 115 dizygotic twin pairs, and one marker (D9S942) was genotyped in 103 monozygotic twin pairs, all of whom had been phenotyped for nevus density.
In summary, we demonstrated a significant inverse correlation between p14ARF protein expression and progression of melanocytic tumors since the amount of p14ARF protein staining decreased from benign melanocytic nevi to metastatic melanoma in situ.
The previously described Met53IleCDKN2A mutation located in exon 2 was detected in a female patient with melanoma metastatic to the regional lymph nodes, multiple primary cutaneous lesions, atypical naevi and a first-degree relative with melanoma.
Here we evaluate 21 melanocytic lesions at various stages of malignant progression from common melanocytic nevi to metastatic melanomas and examine these lesions for Id1 and p16/Ink4a expression.
To further test its role in sporadic melanoma, the expression of p16INK4-protein and -mRNA was characterized in melanomas and melanocytic nevi by immunocytochemistry and in situ reverse transcriptase-polymerase chain reaction.