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光动力疗法前后人体皮肤癌前病变的临床、组织病理学和免疫组织化学评估。

Clinical, histopathological and immunohistochemical assessment of human skin field cancerization before and after photodynamic therapy.

机构信息

Department of Dermatology, Regensburg University Hospital, Regensburg, Germany.

出版信息

Br J Dermatol. 2012 Jul;167(1):150-9. doi: 10.1111/j.1365-2133.2012.10887.x. Epub 2012 Jun 1.

DOI:10.1111/j.1365-2133.2012.10887.x
PMID:22329784
Abstract

BACKGROUND

The field cancerization concept in photodamaged patients suggests that the entire sun-exposed surface of the skin has an increased risk for the development of (pre)-malignant lesions, mainly epithelial tumours. Topical photodynamic therapy (PDT) is a noninvasive therapeutic method for multiple actinic keratosis (AK) with excellent outcome.

OBJECTIVES

To evaluate the clinical, histological and immunohistochemical changes in human skin with field cancerization after multiple sessions of PDT with methyl-aminolaevulinate (MAL).

METHODS

Twenty-six patients with photodamaged skin and multiple AK on the face received three consecutive sessions of MAL-PDT with red light (37 J cm(-2)), 1 month apart. Biopsies before and 3 months after the last treatment session were taken from normal-appearing skin on the field-cancerized area. Immunohistochemical stainings were performed for TP-53, procollagen-I, metalloproteinase-1 (MMP-1) and tenascin-C (Tn-C).

RESULTS

All 26 patients completed the study. The global score for photodamage improved considerably in all patients (P < 0·001). The AK clearance rate was 89·5% at the end of the study. Two treatment sessions were as effective as three MAL-PDT sessions. A significant decrease in atypia grade and extent of keratinocyte atypia was observed histologically (P < 0·001). Also, a significant increase in collagen deposition (P = 0·001) and improvement of solar elastosis (P = 0·002) were noticed after PDT. However, immunohistochemistry showed only a trend for decreased TP-53 expression (not significant), increased procollagen-I and MMP-1 expressions (not significant) and an increased expression of Tn-C (P = 0·024).

CONCLUSIONS

Clinical and histological improvement in field cancerization after multiple sessions of MAL-PDT is proven. The decrease in severity and extent of keratinocyte atypia associated with a decreased expression of TP-53 suggest a reduced carcinogenic potential of the sun-damaged area. The significant increase of new collagen deposition and the reduction of solar elastosis explain the clinical improvement of photodamaged skin.

摘要

背景

光损伤患者的肿瘤多灶性概念表明,整个暴露于阳光的皮肤表面发生(前期)恶性病变的风险增加,主要是上皮肿瘤。局部光动力疗法(PDT)是一种非侵入性治疗方法,可用于治疗多种光化性角化病(AK),效果极佳。

目的

评估多次 5-氨基酮戊酸(MAL)光动力疗法(PDT)治疗光化性损伤皮肤和多发性 AK 后,人类皮肤肿瘤多灶性的临床、组织学和免疫组织化学变化。

方法

26 例光损伤皮肤伴面部多发性 AK 的患者接受了 3 次连续的 MAL-PDT 治疗,间隔 1 个月,红光(37 J/cm(-2))。在最后一次治疗后 3 个月,从肿瘤多灶性区域的正常外观皮肤处取活检。对 TP-53、原胶原蛋白-I、基质金属蛋白酶-1(MMP-1)和 tenascin-C(Tn-C)进行免疫组织化学染色。

结果

所有 26 例患者均完成了研究。所有患者的光损伤整体评分均显著改善(P < 0.001)。研究结束时,AK 清除率为 89.5%。两次治疗与三次 MAL-PDT 治疗一样有效。组织学上观察到异型性分级和角质形成细胞异型性程度显著降低(P < 0.001)。此外,PDT 后还观察到胶原沉积显著增加(P = 0.001)和太阳弹性纤维变性改善(P = 0.002)。然而,免疫组织化学仅显示 TP-53 表达减少的趋势(无统计学意义)、原胶原蛋白-I 和 MMP-1 表达增加(无统计学意义)和 Tn-C 表达增加(P = 0.024)。

结论

多次 MAL-PDT 治疗后肿瘤多灶性的临床和组织学改善得到证实。角质形成细胞异型性严重程度和范围的降低与 TP-53 表达降低相关,提示日光损伤区域的致癌潜能降低。新胶原沉积的显著增加和太阳弹性纤维变性的减少解释了光损伤皮肤的临床改善。

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