Chilosi Marco, Zamò Alberto, Brighenti Antonietta, Malpeli Giorgio, Montagna Licia, Piccoli Paola, Pedron Serena, Lestani Maurizio, Inghirami Giorgio, Scarpa Aldo, Doglioni Claudio, Menestrina Fabio
Department of Pathology, University of Verona, Policlinico G.B.Rossi, 37134 Verona, Italy.
Virchows Arch. 2003 Aug;443(2):175-83. doi: 10.1007/s00428-003-0857-4. Epub 2003 Jul 8.
p63, a member of the p53 family, is involved in the survival and differentiation of reserve/stem cells in different epithelia. To unveil the possible role of p63 in thymic physiology and pathology, we investigated the expression of p63 isoforms in normal thymus, thymomas and other mediastinal tumours. All samples were analysed using immunohistochemistry with three different antibodies: 4A4 antibody recognising all p63 isoforms, p40 antibody reacting only with truncated dominant-negative isoforms (DeltaN-p63) and H-129 antibody recognising all alpha-isoforms. Reverse-transcription polymerase chain reaction (RT-PCR), and real-time PCR analyses were performed on RNA extracted from frozen samples of four thymomas and two primary-mediastinal large-B-cell lymphoma (PMLBCL). In normal thymus, DeltaN-p63alpha was expressed in all cortical and medullary epithelial cells, with decreasing intensity in Hassall's corpuscles. This phenotype was conserved in neoplastic transformation since all 54 investigated thymomas (World Health Organization types A, AB, B1, B2, B3, C) expressed DeltaN-p63alpha (virtually 100% cells). The predominance of DeltaN-p63alpha isoform mRNA was confirmed by real-time PCR. Among other mediastinal tumours, DeltaN-p63alpha was only expressed in those displaying either a stratified epithelial component (teratomas) or epidermoid differentiation (lung carcinoma). Among lymphomas, T-cell-precursor lymphomas did not express p63, whereas most PMLBCL expressed TA-p63alpha (7/8).
p63是p53家族的成员之一，参与不同上皮组织中储备/干细胞的存活和分化。为了揭示p63在胸腺生理和病理中的可能作用，我们研究了p63异构体在正常胸腺、胸腺瘤和其他纵隔肿瘤中的表达。所有样本均使用三种不同抗体进行免疫组织化学分析：4A4抗体可识别所有p63异构体，p40抗体仅与截短的显性负性异构体（DeltaN-p63）反应，H-129抗体可识别所有α异构体。对从四个胸腺瘤和两个原发性纵隔大B细胞淋巴瘤（PMLBCL）的冷冻样本中提取的RNA进行逆转录聚合酶链反应（RT-PCR）和实时PCR分析。在正常胸腺中，DeltaN-p63α在所有皮质和髓质上皮细胞中均有表达，在哈氏小体中的表达强度逐渐降低。这种表型在肿瘤转化中得以保留，因为所有54例研究的胸腺瘤（世界卫生组织A、AB、B1、B2、B3、C型）均表达DeltaN-p63α（几乎100%的细胞）。实时PCR证实了DeltaN-p63α异构体mRNA的优势。在其他纵隔肿瘤中，DeltaN-p63α仅在那些具有分层上皮成分（畸胎瘤）或表皮样分化（肺癌）的肿瘤中表达。在淋巴瘤中，T细胞前体淋巴瘤不表达p63，而大多数PMLBCL表达TA-p63α（7/8）。
