The p53 homologue p73 is overexpressed in many tumors, including lung cancer. We 
have evaluated the differential expression and subcellular localization of the 
functionally distinct apoptotic (TA) and anti-apoptotic (DeltaN) isoforms of p73 
in non-small cell lung cancer (NSCLC), their possible association with p53 
expression and determined the methylation status of the two p73 gene promoters 
(P1 and P2) in this tumor type. Immunohistochemical analysis showed that both 
isoforms are expressed in the majority of cases. However, the oncogenic DeltaN 
variant, derived from the transcripts DeltaN'p73 (from P1) and/or DeltaNp73 
(from P2), is localized mainly in the nucleus, while the anti-oncogenic TAp73 
isoform (derived from a P1 transcript) is sequestered in the cytoplasm in almost 
all cases analyzed. Significant correlation was found between p53 and DeltaNp73 
expression (p=0.041). Methylation analysis conducted on 41 tumor samples showed 
that the P1 promoter is almost invariably unmethylated (39/41 cases) whereas P2 
was found completely methylated in 17 cases and partially or totally 
unmethylated in 24 samples. No correlation was found between the methylation 
status of P1 and P2 and p73 expression. Our results demonstrate that both 
isoforms contribute to p73 overexpression in NSCLC and suggest that their 
different intracellular localization may reflect an alteration of the functional 
p53-p73 network that might contribute to lung cancer development.