p63 in Laryngeal Squamous Cell Carcinoma: Evidence for a Role of TA-p63 Down-Regulation in Tumorigenesis and Lack of Prognostic Implications of p63 Immunoreactivity
p63 in Laryngeal Squamous Cell Carcinoma: Evidence for a Role of TA-p63 Down-Regulation in Tumorigenesis and Lack of Prognostic Implications of p63 Immunoreactivity
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p63 在喉鳞状细胞癌中的作用：TA-p63 下调在肿瘤发生中作用的证据以及 p63 免疫反应性缺乏预后意义
作者：
G. Pruneri;L. Pignataro;M. Manzotti;N. Carboni;D. Ronchetti;A. Neri;B. Cesana;G. Viale
P63是一种与P53相关的基因，其编码的多个转录产物具有(TA-P63)或不具有(ΔN-P63)反式激活P53反应基因的特性。我们首次评估了喉鳞状细胞癌(LSCCs)中p63免疫反应(IR)和mRNA表达的患病率及其临床意义。此外，我们还评估了P63的表达与P53基因状态的关系。P63IR在非肿瘤性上皮的基底层和异型上皮的全层均有表达。其中28例(18.7%)≤中有50%的肿瘤细胞表达p63-IR。ΔN-p63mRNA转录本在23例肿瘤中均有表达，而TA-p63mRNA转录本缺失5例(21.7%)。82例中有24例(29.2%)有p53基因突变，108例中有58例(53.7%)有p53基因突变，两者均与p63-IR无关。未发现p63IR与患者生存期显著相关。有趣的是，TA-p63mRNA水平下调在T3-T4肿瘤和临床晚期患者中更为普遍。尽管这些患者的癌症死亡风险较高(40%对16.6%)，但这种差异并未达到统计学意义。我们的结果提示，P63的异常表达可能参与了喉癌发生的早期阶段，而与P53基因状态无关，而TA-P63mRNA表达下调可能与喉鳞癌患者的临床相关。
p63 is a p53-related gene that encodes for multiple mRNA transcripts with (TA-p63) or without (ΔN-p63) transactivating properties on p53-responsive genes. We evaluated for the first time the prevalence and clinical implications of p63 immunoreactivity (IR) and mRNA expression in laryngeal squamous cell carcinomas (LSCCs). Moreover, we also assessed the relationships between p63 expression and p53 gene status. p63 IR was detectable in the basal cell layers of non-neoplastic epithelium and in the whole thickness of dysplastic epithelium. All the 150 LSCCs analyzed were immunoreactive for p63, with 28 (18.7%) cases showing p63 IR in ≤50% of neoplastic cells. ΔN-p63 mRNA transcripts were detected in all the 23 tumors analyzed, whereas TA-p63 mRNA transcripts were absent in 5 (21.7%) cases. p53 gene mutations were found in 24 (29.2%) of the 82 cases analyzed and p53 IR was found in 58 (53.7%) of the 108 cases analyzed; neither was associated with p63 IR. No significant association was found between p63 IR and patients' survival. Interestingly, down-regulation of TA-p63 mRNA levels was more prevalent in patients with T3-T4 tumors and advanced clinical stage. Although the risk of death for cancer was higher in these patients (40% versus 16.6%), this difference did not reach statistical significance. Our results suggest that abnormal expression of p63 may be involved in the early phases of laryngeal tumorigenesis irrespective of p53 gene status and that TA-p63 mRNA down-regulation, but not p63 IR, may be clinically relevant in patients with LSCC.
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乳腺癌中 β(1C) 整合素的下调与高增殖分数、高组织学分级和较大尺寸相关。
DOI：
10.1016/s0002-9440(10)64716-5
发表时间：
2000
期刊：
The American journal of pathology
影响因子：
--
作者：
Manzotti,M;Dell'Orto,P;Maisonneuve,P;Fornaro,M;Languino,LR;Viale,G
通讯作者：
Viale,G
影响因子：
4
作者：
M. Levrero;V. Laurenzi;A. Costanzo;J. Gong;J. Wang;G. Melino
通讯作者：
M. Levrero;V. Laurenzi;A. Costanzo;J. Gong;J. Wang;G. Melino
影响因子：
11.2
作者：
Y. Suliman;Oliver G. Opitz;Anjali Narayan Avadhani;Timothy C. Burns;W. El-Deiry;David T.W. Wong;Anil K. Rustgi
通讯作者：
Y. Suliman;Oliver G. Opitz;Anjali Narayan Avadhani;Timothy C. Burns;W. El-Deiry;David T.W. Wong;Anil K. Rustgi
影响因子：
3.3
作者：
Wang, TY;Chen, BF;Crum, CP
通讯作者：
Crum, CP