Stretch J R, Gatter K C, Ralfkiaer E, Lane D P, Harris A L
Nuffield Department of Surgery, University of Oxford, Radcliffe Infirmary, UK.
Cancer Res. 1991 Nov 1;51(21):5976-9.
Mutant p53 has been noted in a variety of human malignancies including carcinomas of lung, breast, and colon, which have also been reported to have frequent karyotype anomalies involving the locus of the p53 gene (17p13). Whereas chromosomal abnormalities of chromosomes 1, 6, and 7 have been noted previously in melanoma, frequent aberrations in chromosome 17 have not been reported previously. Due to the common mutation of this locus in so many types of neoplasms, a range of melanomas from different stages of tumor progression were examined immunohistochemically for expression of mutant p53, in order to assess its prevalence and consider the role of this oncogene in the biological progression of melanoma. Forty-five of 53 (85%) specimens from a range of primary and metastatic melanomas were found to have detectable evidence of p53 gene mutation, by virtue of the immunohistochemical detection of mutant p53 protein. Significantly increased prevalence of mutant p53 was found in metastatic melanoma, compared with primary tumors (P less than 0.05). These findings represent one of the highest incidences of this oncogenic mutation yet recorded in a human malignancy and support the concept that p53 may have a functional role in development of the metastatic tumor phenotype.
在包括肺癌、乳腺癌和结肠癌在内的多种人类恶性肿瘤中均已发现突变型p53,这些肿瘤也被报道经常出现涉及p53基因位点(17p13)的核型异常。虽然先前在黑色素瘤中已发现1号、6号和7号染色体的染色体异常,但先前尚未报道17号染色体频繁出现畸变。由于该位点在多种肿瘤类型中普遍发生突变,因此对一系列处于肿瘤进展不同阶段的黑色素瘤进行免疫组织化学检查,以检测突变型p53的表达,从而评估其普遍性,并探讨该癌基因在黑色素瘤生物学进展中的作用。通过免疫组织化学检测突变型p53蛋白,发现53例原发性和转移性黑色素瘤标本中有45例(85%)存在可检测到的p53基因突变证据。与原发性肿瘤相比,转移性黑色素瘤中突变型p53的发生率显著增加(P<0.05)。这些发现代表了这种致癌突变在人类恶性肿瘤中迄今所记录的最高发生率之一,并支持p53可能在转移性肿瘤表型的发展中发挥功能性作用这一概念。