Nuclear Reactivity Relationship Among p53 and Some of its Downstream Proteins is Predictive of p53 Functional State

Our knowledges and opinions on p53 have radically changed since its identification. It is becoming clear that its oncogenic properties are linked to its lost of activity as transcription factor. Recent observation on hot spot mutations of P53 have laid stress that mutations outside functional regions do not inhibit its physiological role. This suggest that the down stream proteins induced by activated p53 could be indirect indicators of p53 state. To solve the issue a group of primary cutaneous T cell lymphomas were studied for the phenotypical expression of p21 and mdm-2 (two nuclear proteins preferentially transcripted by wild type P53), relating their expression to nuclear P53. Our results, beyond low frequency of p53 mutation in CTCL, show the high heterogeneity of nuclear expression of these proteins, but also that constant and quite similar espression of p53 and p2i, though this letter protein has been observed down-regulated in bcl-2 positive disorders, with an intermediate mdm-2 staining could be indicative of a wild type P53. In conclusion, immunohistochemical evaluation of p53 and the relationship with its down-stream proteins (p21 and mdm-2) might be used as a screening method to detect neoplasia with high suspicious of p53 mutation.