In situ assessment of PI3K and PTEN alterations in mycosis fungoides: correlation with clinicopathological features.
Deregulated signalling through phosphatidylinositol 3-kinase (PI3K) 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 PI3K at the protein and at the DNA level as well as the presence of AKT1 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 AKT1 mutation, no PI3KCA copy number gain, only 1 case with PI3KCA 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 PI3K/AKT signalling pathway due to PTEN alterations is rarely attributed to abnormalities in PTEN, PI3K, and AKT1 genes, PTEN mutations exert a negative effect on patients' prognosis with tumours.
['Papadavid|Evangelia|E|', 'Korkolopoulou|Penelope|P|', 'Levidou|Georgia|G|', 'Saetta|Angelica A|AA|', 'Papadaki|Theodora|T|', 'Siakantaris|Marina|M|', 'Nikolaou|Vassiliki|V|', 'Oikonomidi|Afroditi|A|', 'Chatziandreou|Ilenia|I|', 'Marinos|Leonidas|L|', 'Kolialexi|Aggeliki|A|', 'Stratigos|Alexandros|A|', 'Rigopoulos|Dimitrios|D|', 'Psyrri|Amanta|A|', 'Patsouris|Eftratios|E|', 'Antoniou|Christina|C|']
D004252:DNA Mutational Analysis D006801:Humans D007150:Immunohistochemistry D009154:Mutation D009182:Mycosis Fungoides D009687:Nuclear Proteins D051059:PTEN Phosphohydrolase D058539:Phosphatidylinositol 3-Kinase D051057:Proto-Oncogene Proteins c-akt D015398:Signal Transduction D012878:Skin Neoplasms D014157:Transcription Factors
PI3K PTEN mycosis fungoides molecular analysis immunohistochemistry