Basolo F, Pinchera A, Fugazzola L, Fontanini G, Elisei R, Romei C, Pacini F
Istituto di Anatomia Patologica, University of Pisa, Italy.
Eur J Cancer. 1994;30A(2):171-4. doi: 10.1016/0959-8049(94)90081-7.
We studied the expression of p21, the ras encoded protein, in primary tumour of 45 patients with papillary thyroid cancer (PTC). Patients were grouped according to outcome so that one group (31 patients) had a good outcome and the other (14 patients) a fatal outcome, after a follow-up of at least 5 years. The presence of p21 ras protein was assessed by immunohistochemistry with a specific monoclonal antibody (MAb Y-13259). The results were correlated with the outcome, with the expression of proliferating cell nuclear antigen (PCNA)/cyclin (as a marker of cell proliferation) and with other well established prognostic factors for PTC (age, grading, extension and tumour size; Endocrinol Metab Clin North Am 1990, 19, 545-576). p21 staining in tumours of living patients was negative in 15, weakly positive (1+) in 10 and strongly positive (2+ or more) in 6 patients. In tumours from deceased patients, p21 staining was negative in 1, weakly positive in 2 and strongly positive in the remaining 11 patients (P < 0.001, chi 2). PCNA immunostaining was increased in 63.6% (7/11) of the tumours from deceased patients compared to 17.8% (5/28) of the tumours of living patients, but no direct correlation was found between p21 and PCNA expression. Among the other prognostic factors studied, only age > or = 40 years was a significant predictor of poor outcome. The survival curve of patients with strongly positive p21 staining was similar to that of patients aged > or = 40 years at the time of diagnosis. The combination of p21 > or = 2+ and age > or = 40 was superior to age alone (P < 0.05) as a prognostic indicator of poor outcome. In conclusion, our results indicate that the p21 product of the ras (proto)oncogene is differently expressed in PTC, in relation to the degree of aggressiveness. Regardless of the pathogenetic role of the ras oncogene in thyroid tumorigenesis, our data indicate that the expression of the p21 ras protein may be regarded as a prognostic indicator in PTC. Furthermore, overexpression of p21 ras protein is associated with patients in the older age groups, and might contribute to the poor prognosis of elderly patients.
我们研究了45例甲状腺乳头状癌（PTC）患者原发肿瘤中p21（一种由ras基因编码的蛋白质）的表达情况。根据预后情况将患者分组，在至少5年的随访后，一组（31例患者）预后良好，另一组（14例患者）预后不良。采用特异性单克隆抗体（MAb Y - 13259）通过免疫组织化学法评估p21 ras蛋白的存在情况。将结果与预后、增殖细胞核抗原（PCNA）/细胞周期蛋白的表达（作为细胞增殖的标志物）以及其他已确定的PTC预后因素（年龄、分级、肿瘤范围和肿瘤大小；《北美内分泌代谢临床》1990年，第19卷，545 - 576页）进行关联分析。存活患者肿瘤中的p21染色，15例为阴性，10例为弱阳性（1 +），6例为强阳性（2 +或更强）。在死亡患者的肿瘤中，1例p21染色为阴性，2例为弱阳性，其余11例为强阳性（P < 0.001，卡方检验）。与存活患者肿瘤中17.8%（5/28）相比，死亡患者肿瘤中有63.6%（7/11）的PCNA免疫染色增加，但未发现p21与PCNA表达之间存在直接关联。在所研究的其他预后因素中，只有年龄≥40岁是预后不良的显著预测指标。p21染色强阳性患者的生存曲线与诊断时年龄≥40岁患者的生存曲线相似。p21≥2 +且年龄≥40岁作为预后不良的预测指标优于单独的年龄因素（P < 0.05）。总之，我们的结果表明，ras（原）癌基因的p21产物在PTC中的表达与侵袭程度有关。无论ras癌基因在甲状腺肿瘤发生中的致病作用如何，我们的数据表明p21 ras蛋白的表达可被视为PTC的预后指标。此外，p21 ras蛋白的过表达与老年患者相关，可能导致老年患者预后不良。
