Zhang S Y, Ruggeri B, Agarwal P, Sorling A F, Obara T, Ura H, Namiki M, Klein-Szanto A J
Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pa. 19111.
Arch Pathol Lab Med. 1994 Feb;118(2):150-4.
Alterations in the p53 tumor suppressor gene are involved in the pathogenesis of diverse human cancers. Immunohistochemical detection of the p53 protein has been strongly correlated with mutations in the p53 gene. Fifty-four human exocrine pancreatic tumors of American, Japanese, and Senegalese origin and six xenotransplanted human pancreatic carcinoma cell lines were investigated immunohistochemically with monoclonal anti-p53 antibodies pAb 1801 and BP53-12. Positive nuclear p53 immunoreactivity was detected in 37% of paraffin-embedded primary tumors (21.8% in the Japanese group, 52.6% in the American group) and in 50% of xenotransplanted carcinoma cell lines. Since several intraductal papillary adenocarcinomas exhibited positive p53 immunostain, it seems probable that alterations in this tumor suppressor gene occur relatively early in the process of pancreatic carcinogenesis. No clear correlation was established between p53-positive immunohistochemical staining and tumor stage and histologic appearance, nor with patient age, sex, or survival time. In contrast to ductal carcinomas and intraductal papillary adenocarcinomas, none of the mucinous or adenosquamous pancreatic carcinomas exhibited positive nuclear staining for p53. The fact that more than half of the ethanol-fixed fine-needle aspirates were positive for p53 suggests that this type of immunostain may be of potential diagnostic significance. An investigation of a large series of pancreatic tumors is needed to further evaluate the relationship between p53 alterations and clinicopathologic features in human pancreatic cancer.
p53肿瘤抑制基因的改变参与了多种人类癌症的发病机制。p53蛋白的免疫组化检测与p53基因突变密切相关。我们用单克隆抗p53抗体pAb 1801和BP53-12对54例源于美国、日本和塞内加尔的人类外分泌性胰腺肿瘤以及6株异种移植的人类胰腺癌细胞系进行了免疫组化研究。在37%的石蜡包埋原发性肿瘤中检测到p53核阳性免疫反应(日本组为21.8%,美国组为52.6%),在50%的异种移植癌细胞系中也检测到。由于一些导管内乳头状腺癌表现出p53免疫染色阳性,看来这种肿瘤抑制基因的改变可能在胰腺癌发生过程中相对较早出现。p53免疫组化阳性染色与肿瘤分期、组织学表现之间未建立明确的相关性,与患者年龄、性别或生存时间也无相关性。与导管癌和导管内乳头状腺癌不同,黏液性或腺鳞癌性胰腺癌均未表现出p53核染色阳性。超过一半的乙醇固定细针穿刺抽吸物p53呈阳性这一事实表明,这种免疫染色类型可能具有潜在的诊断意义。需要对大量胰腺肿瘤进行研究,以进一步评估p53改变与人类胰腺癌临床病理特征之间的关系。