Beclin 1 and LC3 autophagic gene expression in cutaneous melanocytic lesions.
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.
Miracco
Clelia
C
Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy. miracco@unisi.it
Cevenini
Gabriele
G
Franchi
Alessandro
A
Luzi
Pietro
P
Cosci
Elena
E
Mourmouras
Vasileios
V
Monciatti
Irene
I
Mannucci
Susanna
S
Biagioli
Maurizio
M
Toscano
Marzia
M
Moretti
Daniele
D
Lio
Roberto
R
Massi
Daniela
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D001343:Autophagy; D000071186:Beclin-1; D004416:Dysplastic Nevus Syndrome / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009508:Nevus, Pigmented / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins