Poly(adenosine diphosphate-ribose) polymerase 1 expression in malignant melanomas from photoexposed areas of the head and neck region

• Published in: Human pathology 2005-07, Vol.36 (7), p.724-731
• Main Authors: Staibano, Stefania, Pepe, Stefano, Muzio, Lorenzo Lo, Somma, Pasquale, Mascolo, Massimo, Argenziano, Giuseppe, Scalvenzi, Massimiliano, Salvatore, Gaetano, Fabbrocini, Gabriella, Molea, Guido, Bianco, Angelo Raffaele, Carlomagno, Chiara, De Rosa, Gaetano
• Format: Article
• Language: English
• Subjects: Adenosine; Adolescent; Adult; Aged; Apoptosis; Biological and medical sciences; Blotting, Western; Cancer therapies; Carcinogens; Cutaneous melanoma; Deoxyribonucleic acid; Dermatology; Disease Progression; DNA; DNA damage; DNA repair; Drug resistance; Female; Head and Neck Neoplasms - enzymology; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - pathology; Humans; Immunoenzyme Techniques; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Melanoma - enzymology; Melanoma - mortality; Melanoma - secondary; Middle Aged; Neoplasms, Radiation-Induced - enzymology; Neoplasms, Radiation-Induced - mortality; Neoplasms, Radiation-Induced - pathology; PARP-1; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases - metabolism; Prognosis; Proteins; Risk factors; Skin cancer; Skin Neoplasms - enzymology; Skin Neoplasms - mortality; Skin Neoplasms - pathology; Survival Rate; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Ultraviolet Rays
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2005.04.017

The family of the poly(adenosine diphosphate-ribose) polymerase (PARP) proteins is directly involved in genomic stability, DNA repair, and apoptosis by DNA damage. In this study, we evaluated the role of PARP-1 in melanoma and its prognostic importance. We studied by immunohistochemistry and Western blot analysis PARP-1 expression in a selected series of 80 primary melanoma of the head and neck region. The results were correlated with tumor thickness and patient's outcome. A follow-up of at least 3 years was available. Fifteen cases of benign melanocytic nevi were used as controls. Normal melanocytes showed only scattered, focal nuclear positivity and were considered as negative for PARP-1 expression by immunohistochemistry (score, 0). Thirty cases of melanoma (37.5%) showed nuclear expression of PARP-1 in both radial and vertical growth phases. Western blot analysis showed the presence of a high signal for full-length PARP-1 only in the cases with high immunohistochemical (nuclear) expression of protein (score, ++/+++) in both radial and vertical growth phase. A significant correlation was present between PARP-1 expression in vertical growth phase and the thickness of tumor lesion ( P = .014); all but one tumor measuring less than 0.75 mm showed no or low PARP-1 expression. No correlation was found between PARP-1 expression in radial growth phase and tumor thickness ( P = .38, data not shown). These data suggest that PARP-1 overexpression is a potential novel molecular marker of aggressive cutaneous malignant melanoma and a direct correlation between PARP-1–mediated inhibition of the apoptosis and biologic behavior of cutaneous malignant melanoma.