Simms W W, Ordóñez N G, Johnston D, Ayala A G, Czerniak B
Department of Pathology, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Cancer. 1995 Jul 15;76(2):223-7. doi: 10.1002/1097-0142(19950715)76:2<223::aid-cncr2820760210>3.0.co;2-4.
p53 acts as a tumor suppressor gene because of to its negative control of the cell cycle and its central role in programmed cell death. It frequently is mutated, as observed in a variety of human neoplasms. The mutations inhibit tumor-suppressor activities of p53, which may gain a new function of tumor promotion. In this study, p53 was investigated in various components of dedifferentiated chondrosarcoma and correlated with their proliferative activities.
Immunohistochemical assays for p53, Ki-67, and proliferating cell nuclear antigen (PCNA) were used in a series of eight dedifferentiated chondrosarcomas of bone. The cartilaginous component was low grade (Grade I-II) in five cases. It was predominantly low grade with foci of a high grade (Grade III) chondrosarcoma in the remaining three cases. The noncartilaginous (dedifferentiated) high grade component consisted of malignant fibrous histiocytoma in five cases and osteosarcoma in three.
Regardless of the histological type, diffuse strong nuclear staining for p53 occurred in the high grade noncartilaginous component of all eight of the tumors. The low grade cartilaginous component of six cases was negative for p53, with focal weak staining in the two remaining cases. The high grade cartilaginous component showed strong positive staining for this protein in all three cases. Ki-67 and PCNA expression were similar to that of p53.
The percentage of p53 positive staining roughly was parallel to the proliferating fraction of cells in various components of dedifferentiated chondrosarcoma. Moreover, p53 overexpression was consistently present in the high grade noncartilaginous (dedifferentiated) component of the tumor and was accompanied by increased proliferative activity.
p53作为一种肿瘤抑制基因,因其对细胞周期的负调控作用以及在程序性细胞死亡中的核心作用。在多种人类肿瘤中经常观察到它发生突变。这些突变抑制了p53的肿瘤抑制活性,p53可能获得促进肿瘤的新功能。在本研究中,对去分化软骨肉瘤的各个成分进行了p53检测,并将其与它们的增殖活性相关联。
对一系列8例骨去分化软骨肉瘤进行p53、Ki-67和增殖细胞核抗原(PCNA)的免疫组织化学检测。5例软骨成分属于低级别(I-II级)。其余3例主要为低级别软骨肉瘤,伴有高级别(III级)软骨肉瘤灶。非软骨(去分化)高级别成分中,5例为恶性纤维组织细胞瘤,3例为骨肉瘤。
无论组织学类型如何,所有8例肿瘤的高级别非软骨成分中均出现p53弥漫性强核染色。6例低级别软骨成分p53呈阴性,其余2例有局灶性弱阳性染色。所有3例高级别软骨成分中该蛋白均呈强阳性染色。Ki-67和PCNA表达与p53相似。
p53阳性染色百分比大致与去分化软骨肉瘤各成分中的细胞增殖分数平行。此外,p53过表达始终存在于肿瘤的高级别非软骨(去分化)成分中,并伴有增殖活性增加。