Different Prevalence of Transactivating (TA) p63 and Non-TAp63 Isoforms in Pulmonary Adenocarcinomas: A Useful Diagnostic Tool
G Pelosi, A Sonzogni, M Papotti, L Righi, G Rossi, G Viale. European Institute of Oncology and University of Milan School of Medicine, Milan, Italy; University of Turin, Orbassano Hospital, Turin, Italy; Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy
Background: p63 protein, a member of the p53 family of nuclear transcription factors, is a fundamental player in the development of pulmonary squamous cell carcinomas (PSSCs), but little is known about the prevalence of different p63 isoforms in pulmonary adenocarcinomas (PACs).
Design: We assessed twenty PACs for p63 by using immunohistochemistry on paraffin sections with 1A4 clone, recognizing all p63 isoforms, and p40 polyclonal antibody recognizing all non-TA p63 isoforms. Moreover, paired frozen samples of the same tumors were analyzed by real-time PCR assay for the 10 different p63 isoforms thus far recognized (α, β, γ, δ, ε), of either TA or non-TA type. A few PSCCs were used as controls for assays.
Results: p63 immunoreactivity with clone 1A4 was found in 15% of PACs (range 10-70% tumor cells), independent of growth patterns, whereas none exhibited p40 immunostain, revealing a strong prevalence of TA isoforms. PSCCs were always diffusely positive for both 1A4 and p40 antibodies. Real-time PCR analysis confirmed that TA isoforms prevailed by far on non-TA isoforms in PACs (with a prevalence of α over β), whereas the reverse held true for PSCCs (with a prevalence of α over β, γ and δ, in that order). In turn, ε isoform was never found in either PACs or PSCCs.
Conclusions: The absence of p40 immunoreactivity in PACs, paralleling a strong prevalence of TA isoforms, may be a useful diagnostic clue when the distinction from PSCCs is crucial for neoadjuvant therapy, for example in the setting of poorly differentiated tumors and/or small biopsies.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 241, Wednesday Morning