B Bellei1, C Cota, A Amantea, L Muscardin, M Picardo. 1. Laboratory of Cutaneous Physiopathology, San Gallicano Dermatological Institute IRCCS, Via di San Gallicano 25A, Rome, Italy. citolab@ifo.it
Abstract
BACKGROUND: Aberrant activation of beta-catenin contributes to the onset of a variety of tumours. There are many tumours that display beta-catenin accumulation in the absence of mutations in its gene. Recently, abnormal accumulation of wild-type beta-catenin has been associated with mutational inactivation of the p53 tumour suppressor. OBJECTIVES: To investigate the potential role of p53 and its homologue p63 in beta-catenin deregulation and to correlate this with disease outcome. METHODS: We analysed a panel of 24 samples of mycosis fungoides (MF), the most frequent manifestation of cutaneous T-cell lymphoma (CTCL), for beta-catenin, p53 and p63 protein expression by immunohistochemistry. Based on the immunostaining results for beta-catenin protein, 11 positive cases were selected for laser microdissection, genomic DNA isolation and subsequent mutation analysis of beta-catenin exon 3 and p53 exons 4-8. RESULTS: Our findings revealed overexpression of beta-catenin, p53 and p63 in 46%, 38% and 17% of cases, respectively. The number of p53-positive cases of MF was significantly higher (P < 0.05) in the beta-catenin-positive group (73%). Sequence analysis demonstrated that wild-type beta-catenin accumulation in MF is not associated with mutational inactivation of the p53 gene and, more importantly, our data provide evidence that a common polymorphic form of p53 (Arg72Pro) is significantly associated with beta-catenin overexpression (P < 0.05). No significant differences in the three genotypes were observed between the CTCL cases and the control group, demonstrating that Arg72Pro polymorphism of the p53 gene is not associated with the risk of developing cutaneous lymphomas (P > 0.05). CONCLUSIONS: We found an association of beta-catenin and p53 overexpression without detection of structural alteration in the genes, suggesting that p53 mutation is not an important mechanism for beta-catenin activation in primary CTCL. Additionally, we speculate that the p53 codon 72 polymorphism may influence negative feedback control involving beta-catenin and p53.
BACKGROUND: Aberrant activation of beta-catenin contributes to the onset of a variety of tumours. There are many tumours that display beta-catenin accumulation in the absence of mutations in its gene. Recently, abnormal accumulation of wild-type beta-catenin has been associated with mutational inactivation of the p53tumour suppressor. OBJECTIVES: To investigate the potential role of p53 and its homologue p63 in beta-catenin deregulation and to correlate this with disease outcome. METHODS: We analysed a panel of 24 samples of mycosis fungoides (MF), the most frequent manifestation of cutaneous T-cell lymphoma (CTCL), for beta-catenin, p53 and p63 protein expression by immunohistochemistry. Based on the immunostaining results for beta-catenin protein, 11 positive cases were selected for laser microdissection, genomic DNA isolation and subsequent mutation analysis of beta-catenin exon 3 and p53 exons 4-8. RESULTS: Our findings revealed overexpression of beta-catenin, p53 and p63 in 46%, 38% and 17% of cases, respectively. The number of p53-positive cases of MF was significantly higher (P < 0.05) in the beta-catenin-positive group (73%). Sequence analysis demonstrated that wild-type beta-catenin accumulation in MF is not associated with mutational inactivation of the p53 gene and, more importantly, our data provide evidence that a common polymorphic form of p53 (Arg72Pro) is significantly associated with beta-catenin overexpression (P < 0.05). No significant differences in the three genotypes were observed between the CTCL cases and the control group, demonstrating that Arg72Pro polymorphism of the p53 gene is not associated with the risk of developing cutaneous lymphomas (P > 0.05). CONCLUSIONS: We found an association of beta-catenin and p53 overexpression without detection of structural alteration in the genes, suggesting that p53 mutation is not an important mechanism for beta-catenin activation in primary CTCL. Additionally, we speculate that the p53 codon 72 polymorphism may influence negative feedback control involving beta-catenin and p53.
Authors: Laura Y McGirt; Peilin Jia; Devin A Baerenwald; Robert J Duszynski; Kimberly B Dahlman; John A Zic; Jeffrey P Zwerner; Donald Hucks; Utpal Dave; Zhongming Zhao; Christine M Eischen Journal: Blood Date: 2015-06-16 Impact factor: 22.113
Authors: Briseis Aschebrook-Kilfoy; Pierluigi Cocco; Carlo La Vecchia; Ellen T Chang; Claire M Vajdic; Marshall E Kadin; John J Spinelli; Lindsay M Morton; Eleanor V Kane; Joshua N Sampson; Carol Kasten; Andrew L Feldman; Sophia S Wang; Yawei Zhang Journal: J Natl Cancer Inst Monogr Date: 2014-08
Authors: Fernando Gallardo; Joan Bertran; Erika López-Arribillaga; Jéssica González; Silvia Menéndez; Ignacio Sánchez; Luis Colomo; Mar Iglesias; Marta Garrido; Luis Francisco Santamaría-Babí; Ferran Torres; Ramon M Pujol; Anna Bigas; Lluís Espinosa Journal: Leukemia Date: 2018-02-22 Impact factor: 11.528