Barzilai Aviv, Lyakhovitsky Anna, Trau Henri, Fogel Mina, Huszar Monika
Department of Dermatology, Sheba Medical Center, Tel-Hashomer, Israel.
J Am Acad Dermatol. 2007 Oct;57(4):669-76. doi: 10.1016/j.jaad.2007.04.025.
The evolution of squamous cell carcinoma (SCC) on sun-exposed areas is a multistep process triggered by ultraviolet radiation (UVR), in which precursor lesions exist. However, the exact classification of the various lesions in this process, mainly solar keratosis (SK), is still disputed, and its pathogenesis requires further clarification.
To further elucidate the evolution of SCC on sun-damaged skin by correlating the levels of p53 protein expression, a parameter that reflects UVR damage to cells, and the morphology of the lesions that develop on sun-exposed areas.
Biopsy specimens from normal skin (n = 4), normal skin with various degrees of solar elastosis (SE) (n = 16), various degrees of SK (n = 17) and SCCs from sun-exposed (n = 12) and sun-protected (n = 7) areas were stained with anti-p53 antibodies. A semiquantitative evaluation of the degree of staining was performed and correlated with the histological features.
Nuclear staining in keratinocytes was observed already in normal skin with mild SE and was increased gradually to its highest level of expression in advanced SK. It was also expressed in SCCs, but to a lesser degree. Statistical analysis revealed association between the morphology of the lesion and the level of p53 expression (P < .01); it also showed that in general the level of p53 is correlated with the histology of the lesion (P < .001). Furthermore, with regard to p53 expression, two groups of lesions exist: one showing a low level of expression of p53 that includes normal skin, skin with various degrees of SE and SCC from sun-protected areas, and a second group showing a high level of expression that includes SK and SCC occurring on sun-damaged skin.
This is an immunohistochemical study of relatively few cases and in which the antibody detects all types of p53 protein.
This study furnishes further evidence that the development of SCC on sun-damaged skin is a gradual process not only morphologically but also on the molecular level. The process starts already in normal-appearing epidermis with SE. In that respect, SK should be regarded as a part of the continuum in the development of SCC, analogous to the situation in other epithelia. The molecular events involved in the development of SCC on sun-exposed areas may be different from those involving the development of SCC on sun-protected areas.
暴露于阳光下区域的鳞状细胞癌（SCC）的演变是一个由紫外线辐射（UVR）触发的多步骤过程，在此过程中存在前驱病变。然而，这一过程中各种病变的确切分类，主要是日光性角化病（SK），仍存在争议，其发病机制需要进一步阐明。
通过关联反映UVR对细胞损伤的参数p53蛋白表达水平与暴露于阳光下区域所发生病变的形态，进一步阐明SCC在日光损伤皮肤中的演变。
用抗p53抗体对来自正常皮肤（n = 4）、具有不同程度日光性弹力组织变性（SE）的正常皮肤（n = 16）、不同程度的SK（n = 17）以及来自暴露于阳光下区域（n = 12）和非暴露于阳光下区域（n = 7）的SCC的活检标本进行染色。对染色程度进行半定量评估，并与组织学特征相关联。
在具有轻度SE的正常皮肤中就已观察到角质形成细胞核染色，并且在晚期SK中逐渐增加至其最高表达水平。它也在SCC中表达，但程度较低。统计分析显示病变形态与p53表达水平之间存在关联（P <.01）；还表明一般而言p53水平与病变的组织学相关（P <.001）。此外，关于p53表达，存在两组病变：一组显示p53低表达水平，包括正常皮肤、具有不同程度SE的皮肤以及来自非暴露于阳光下区域的SCC，另一组显示高表达水平，包括发生在日光损伤皮肤的SK和SCC。
这是一项针对相对较少病例的免疫组织化学研究，且该抗体可检测所有类型的p53蛋白。
本研究进一步证明，SCC在日光损伤皮肤中的发生不仅在形态学上而且在分子水平上都是一个渐进过程。该过程在外观正常但有SE的表皮中就已开始。在这方面，SK应被视为SCC发生连续过程的一部分，类似于其他上皮组织的情况。暴露于阳光下区域SCC发生过程中涉及的分子事件可能与非暴露于阳光下区域SCC发生过程中涉及的分子事件不同。
