Ren Z P, Pontén F, Nistér M, Pontén J
Department of Pathology, University Hospital, University of Uppsala, Sweden.
Int J Cancer. 1996 Jun 21;69(3):174-9. doi: 10.1002/(SICI)1097-0215(19960621)69:3<174::AID-IJC4>3.0.CO;2-X.
Specimens of squamous-cell neoplasms (81 invasive cancers, 36 in situ cancers, 70 dysplasias, 5 keratoacanthomas, 19 papillomas) and normal skin were immunostained with p53 antibody. Nuclear accumulation of p53 was visualized as following 2 distinct patterns: dispersed or compact. The former is interpreted as a reversible reaction to sunlight, whereas the latter, after microdissection and sequencing of DNA, has been shown to reflect clonal multiplication of keratinocytes with mutated p53. The dispersed pattern was diffusely distributed and usually only involved a small proportion of epidermal cells. The compact pattern was characterized as a contiguous area of homogeneously stained cells sharply demarcated from its surroundings. It involved patches of normal epidermis or large areas of dysplastic or malignant squamous epithelium. Immature cells were always stained, whereas immunoreactivity was variably present in differentiating keratinocytes. Dispersed patterns occurred in 94.7% of strongly UV-exposed skin (mainly face) and to a lesser extent in less exposed parts of the body. It showed no correlation to the age of the individual. About two-thirds of biopsies from individuals over age 50 displayed compact patterns in sun-exposed, otherwise normal, epidermis. About 65% of pre-malignant and malignant squamous-cell neoplasms had a compact pattern. The presence of p53 immunoreactivity as a compact pattern supports the idea that mutations of the p53 gene are early events in the sequence from dysplasia to invasive squamous-cell cancer of the skin. Also, even in the absence of cellular atypia, patches of epidermal cells can accumulate p53 in a way that is indistinguishable from that of cancer and pre-cancer.
用p53抗体对鳞状细胞肿瘤标本（81例浸润性癌、36例原位癌、70例发育异常、5例角化棘皮瘤、19例乳头状瘤）和正常皮肤进行免疫染色。p53的核聚集呈现为以下两种不同模式：分散型或致密型。前者被解释为对阳光的可逆反应，而后者在对DNA进行显微切割和测序后，已被证明反映了p53突变的角质形成细胞的克隆增殖。分散型模式呈弥漫性分布，通常仅累及一小部分表皮细胞。致密型模式的特征是均匀染色细胞的连续区域与其周围环境有明显界限。它累及正常表皮斑块或发育异常或恶性鳞状上皮的大片区域。未成熟细胞总是被染色，而在分化的角质形成细胞中免疫反应性存在差异。分散型模式出现在94.7%的强烈紫外线暴露皮肤（主要是面部）中，在身体较少暴露部位出现的程度较轻。它与个体年龄无关。50岁以上个体的活检标本中，约三分之二在阳光暴露的、其他方面正常的表皮中呈现致密型模式。约65%的癌前和恶性鳞状细胞肿瘤具有致密型模式。p53免疫反应性以致密型模式存在支持了这样一种观点，即p53基因的突变是皮肤从发育异常到浸润性鳞状细胞癌序列中的早期事件。此外，即使在没有细胞异型性的情况下，表皮细胞斑块也可以以与癌症和癌前病变无法区分的方式积累p53。
