Beclin 1 and LC3 autophagic genes are altered in several human
cancer types. This study was designed to assess the expression of
Beclin 1 and LC3 in cutaneous melanocytic lesions, in which they have not yet been investigated. In
melanoma, we correlated their expression with conventional histopathologic prognostic factors. In 149 lesions, including benign
nevi, dysplastic nevi, radial growth phase
melanomas, vertical growth phase
melanomas, and
melanoma metastases,
proteins were evaluated by immunohistochemistry, and, in representative cases of benign
nevi, vertical growth phase
melanomas and
melanoma metastases were evaluated by Western blotting. In most lesions,
messenger RNA level was also assessed by real-time
reverse transcriptase polymerase chain reaction. Both genes were expressed in all the investigated conditions.
Beclin 1 cytoplasmic
protein and
messenger RNA, as well as LC3
messenger RNA, significantly decreased with
tumor progression (P < .05). The percentage of cases with high cytoplasmic expression of
beclin 1 from 100% in benign
nevi declined to 86.4% in
dysplastic nevi, 54.5% in radial growth phase
melanomas, 54.3% in vertical growth phase
melanomas, and 26.7% in
melanoma metastases. The lowest expression of LC3 II
protein was observed in
melanoma metastases (53.3% of cases) (P < .05); LC3 II
protein overexpression was, however, found in several nonbenign lesions, with the highest percentage (45.5%) in radial growth phase
melanomas. LC3 II
protein expression was inversely correlated to thickness, ulceration, and mitotic rate. In a multivariate analysis, messenger RNAs for both genes discriminated between nonmalignant (benign and
dysplastic nevi) and malignant (radial, vertical growth phase
melanomas, and
melanoma metastases) lesions. Our results, therefore, indicate that
beclin 1 and LC3 II autophagic gene expression is altered also in melanocytic
neoplasms.