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In situ assessment of PI3K and PTEN alterations in mycosis fungoides: correlation with clinicopathological features

Experimental Dermatology2014Vol. 23(12), pp. 931–933

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Evangelia Papadavid, Penelope Korkolopoulou, Georgia Levidou, Angelica A. Saetta, Theodora Papadaki, Marina P. Siakantaris, Vassiliki Nikolaou, A. Oikonomidi, Ilenia Chatziandreou, Leonidas Marinos, Aggeliki Kοlialexi, Alexandros Stratigos, Dimitrios Rigopoulos, A. Psyrri, Eftratios Patsouris, Christina Antoniou

Abstract

Abstract Deregulated signalling through phosphatidylinositol 3‐kinase ( PI 3K) pathway plays a critical role in tumour initiation and progression. We have already shown that AKT is activated in skin lesions in Mycosis Fungoides ( MF ) and we herein further investigate the frequency and clinical significance of PTEN and PI 3K at the protein and at the DNA level as well as the presence of AKT 1 mutations in skin lesions from 50 patients with MF clinical stages I‐ IV in relation to clinicopathological features. Increased p‐ AKT expression correlated with poor prognosis in plaques ( P = 0.0198), whereas p‐ AKT was an independent predictor of poor survival in the entire cohort ( P = 0.017, HR = 1.012). PTEN cytoplasmic expression was found low or absent in all 77.3% of cases and inversely correlated with advanced clinical stages ( P = 0.0744). Molecular analysis showed no AKT 1 mutation, no PI 3 KCA copy number gain, only 1 case with PI 3 KCA mutation in exon 9 and 3 cases with PTEN mutations (7%) in exons 7, 8 and 5. The latter correlated with disease ( P = 0.0253) and progression ( P < 0.0001) free survival in tumour stage. Although activation of PI 3K/ AKT signalling pathway due to PTEN alterations is rarely attributed to abnormalities in PTEN , PI 3K, and AKT 1 genes, PTEN mutations exert a negative effect on patients’ prognosis with tumours.

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Abstract

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