TY - JOUR
T1 - The transactivating isoforms of p63 are overexpressed in high-grade follicular lymphomas independent of the occurence of p63 gene amplification
AU - Pruneri, Giancarlo
AU - Fabris, Sonia
AU - Dell'Orto, Patrizia
AU - Biasi, Maria Olivia
AU - Valentini, Stefano
AU - Del Curto, Barbara
AU - Laszlo, Daniele
AU - Cattaneo, Laura
AU - Fasani, Roberta
AU - Rossini, Laura
AU - Manzotti, Michela
AU - Bertolini, Francesco
AU - Martinelli, Giovanni
AU - Neri, Antonio
AU - Viale, Giuseppe
PY - 2005/7
Y1 - 2005/7
N2 - p63 is a p53-related gene mapping to 3q28 that codes for multiple mRNA transcripts with (TA-p63) or without (ΔN-p63) transactivating effects on genes that promote cell differentiation and apoptosis. We analysed p63 alterations by immunohistochemistry, quantitative real-time RT-PCR and FISH in a series of 45 follicular lymphomas (FL). None of the tumours showed immunoreactivity for the p40 antibody, which recognizes only the truncated isoforms of p63, or ΔN-p63 mRNA expression. Immunoreactivity for the 4A4 antibody, which recognizes both the transactivating and the truncated p63 isoforms, was found in 5 ± 5.5%, 6.85 ± 4.88% and 33.2 ± 22.31% of grade I, II and III FL cells, respectively (p <0.0001). Quantitative RT-PCR analysis showed that all cases but one had TA-p63 mRNA levels higher than non-neoplastic lymphocytes, and that TA-p63 mRNA expression correlated significantly (r = 0.9194, p <0.0001) with the prevalence of p63 immunoreactivity. FISH extra signals for the p63 gene were found in seven (23.3%) of the 30 cases analysed (0/6 grade I, 2/15 grade II and 5/9 grade III; p = 0.01937). Further hybridizations showed a pattern highly suggestive of chromosome 3 polysomy in six cases. One of these cases also bore extra copies of the p63 and bcl-6 genes. Co-localization of p63 and IgH signals was found in one case. No association between the prevalence of p63 immunoreactivity and extra p63 gene signals was detectable when the cases were dichotomized according to a p63 immunoreactivity threshold of 10%. Our data suggest that TA-p63 is overexpressed in high-grade FL, possibly independent of the occurrence of gene abnormalities, and that it may be involved in the highly complex mechanism of regulation of apoptosis of FL cells.
AB - p63 is a p53-related gene mapping to 3q28 that codes for multiple mRNA transcripts with (TA-p63) or without (ΔN-p63) transactivating effects on genes that promote cell differentiation and apoptosis. We analysed p63 alterations by immunohistochemistry, quantitative real-time RT-PCR and FISH in a series of 45 follicular lymphomas (FL). None of the tumours showed immunoreactivity for the p40 antibody, which recognizes only the truncated isoforms of p63, or ΔN-p63 mRNA expression. Immunoreactivity for the 4A4 antibody, which recognizes both the transactivating and the truncated p63 isoforms, was found in 5 ± 5.5%, 6.85 ± 4.88% and 33.2 ± 22.31% of grade I, II and III FL cells, respectively (p <0.0001). Quantitative RT-PCR analysis showed that all cases but one had TA-p63 mRNA levels higher than non-neoplastic lymphocytes, and that TA-p63 mRNA expression correlated significantly (r = 0.9194, p <0.0001) with the prevalence of p63 immunoreactivity. FISH extra signals for the p63 gene were found in seven (23.3%) of the 30 cases analysed (0/6 grade I, 2/15 grade II and 5/9 grade III; p = 0.01937). Further hybridizations showed a pattern highly suggestive of chromosome 3 polysomy in six cases. One of these cases also bore extra copies of the p63 and bcl-6 genes. Co-localization of p63 and IgH signals was found in one case. No association between the prevalence of p63 immunoreactivity and extra p63 gene signals was detectable when the cases were dichotomized according to a p63 immunoreactivity threshold of 10%. Our data suggest that TA-p63 is overexpressed in high-grade FL, possibly independent of the occurrence of gene abnormalities, and that it may be involved in the highly complex mechanism of regulation of apoptosis of FL cells.
KW - FISH
KW - Follicular lymphomas
KW - Immunohistochemistry
KW - p63
KW - RT-PCR
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U2 - 10.1002/path.1787
DO - 10.1002/path.1787
M3 - Article
C2 - 15887287
AN - SCOPUS:21344449113
VL - 206
SP - 337
EP - 345
JO - Journal of Pathology
JF - Journal of Pathology
SN - 0022-3417
IS - 3
ER -