Cutaneous malignant melanoma (CMM) incidence rate and related deaths are increasing faster than most of other skin malignancies with an incidence which has tripled during the last 40 years and continues to grow. Solar damage is the major environmental causal factor in all skin cancers, and intermittent intense exposure to sunlight and/or severe sunburn is also the most important risk factors for CMM. Basic research into UVR showed that DNA-repair via different pathways causes a cascade of cellular phenomena ranging from induction of pigmentation, to immunomodulation, acid radical defence, apoptosis, and oncogenes expression. The members of the poly (ADP-ribose) polymerase (PARP) family proteins are directly involved in genomic stability, DNA repair and cell death triggered by DNA damage. However, their potential role in carcinogenesis has not been well evaluated. We investigated the immunohistochemical expression of PARP-1 nuclear enzyme in a selected series of 80 cases of primary CMM from photo exposed areas, comparing the findings with the tumour thickness and with the follow-up data. Western-blot analysis was also performed on available tissue stored at -80°C from selected cases to confirm the immunohistochemical data. Data analysis showed a positive correlation between immunohistochemical PARP-1 nuclear over expression in both radial and vertical growt phases of CMM and a worse outcome of patients (P<0.05), irrespectively to the Breslow value. The Western-blot analysis showed that PARP-1 over expression was due only to the non-cleaved form of the enzyme. On the contrary, the overexpression of PARP-1 restricted to the vertical growth phase CMM did not showed any statistical correlation with the clinical behaviour of the tumours. Absence of PARP-1 overexpression in both radial and vertical growth phase was instead associated with a good prognosis of CMM. The analysis of PARP-1 expression may allow the detection of a subset of CMM with a more aggressive phenotype, which may benefit of closer follow-up and represents also a possible target for a more aggressive therapy.

POLY (ADP-RIBOSE) POLYMERASE (PARP-1) EXPRESSION IN MALIGNANT MELANOMAS FROM PHOTO EXPOSED AREAS OF THE HEAD AND NECK REGION / Staibano, Stefania; Pepe, Stefano; LO MUZIO, Lorenzo; Somma, P; Argenziano, Giuseppe; Soyer, P; Fabbrocini, Gabriella; Gaetano, S; Mezza, Ernesto; Molea, Guido; Laus, Gianluca; Bianco, Ar; DE ROSA, Gaetano. - (2003). (Intervento presentato al convegno 3th research meeting on melanoma tenutosi a Milan - Italy nel 26-27 Maggio 2003).

POLY (ADP-RIBOSE) POLYMERASE (PARP-1) EXPRESSION IN MALIGNANT MELANOMAS FROM PHOTO EXPOSED AREAS OF THE HEAD AND NECK REGION

STAIBANO, STEFANIA;PEPE, STEFANO;LO MUZIO, LORENZO;ARGENZIANO, GIUSEPPE;FABBROCINI, GABRIELLA;MEZZA, ERNESTO;MOLEA, GUIDO;LAUS, GIANLUCA;DE ROSA, GAETANO
2003

Abstract

Cutaneous malignant melanoma (CMM) incidence rate and related deaths are increasing faster than most of other skin malignancies with an incidence which has tripled during the last 40 years and continues to grow. Solar damage is the major environmental causal factor in all skin cancers, and intermittent intense exposure to sunlight and/or severe sunburn is also the most important risk factors for CMM. Basic research into UVR showed that DNA-repair via different pathways causes a cascade of cellular phenomena ranging from induction of pigmentation, to immunomodulation, acid radical defence, apoptosis, and oncogenes expression. The members of the poly (ADP-ribose) polymerase (PARP) family proteins are directly involved in genomic stability, DNA repair and cell death triggered by DNA damage. However, their potential role in carcinogenesis has not been well evaluated. We investigated the immunohistochemical expression of PARP-1 nuclear enzyme in a selected series of 80 cases of primary CMM from photo exposed areas, comparing the findings with the tumour thickness and with the follow-up data. Western-blot analysis was also performed on available tissue stored at -80°C from selected cases to confirm the immunohistochemical data. Data analysis showed a positive correlation between immunohistochemical PARP-1 nuclear over expression in both radial and vertical growt phases of CMM and a worse outcome of patients (P<0.05), irrespectively to the Breslow value. The Western-blot analysis showed that PARP-1 over expression was due only to the non-cleaved form of the enzyme. On the contrary, the overexpression of PARP-1 restricted to the vertical growth phase CMM did not showed any statistical correlation with the clinical behaviour of the tumours. Absence of PARP-1 overexpression in both radial and vertical growth phase was instead associated with a good prognosis of CMM. The analysis of PARP-1 expression may allow the detection of a subset of CMM with a more aggressive phenotype, which may benefit of closer follow-up and represents also a possible target for a more aggressive therapy.
2003
POLY (ADP-RIBOSE) POLYMERASE (PARP-1) EXPRESSION IN MALIGNANT MELANOMAS FROM PHOTO EXPOSED AREAS OF THE HEAD AND NECK REGION / Staibano, Stefania; Pepe, Stefano; LO MUZIO, Lorenzo; Somma, P; Argenziano, Giuseppe; Soyer, P; Fabbrocini, Gabriella; Gaetano, S; Mezza, Ernesto; Molea, Guido; Laus, Gianluca; Bianco, Ar; DE ROSA, Gaetano. - (2003). (Intervento presentato al convegno 3th research meeting on melanoma tenutosi a Milan - Italy nel 26-27 Maggio 2003).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/493410
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