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P16在暴露于阳光区域的皮肤癌中过度表达。

P16 is overexpressed in cutaneous carcinomas located on sun-exposed areas.

作者信息

Conscience Isabelle, Jovenin Nicolas, Coissard Christelle, Lorenzato Marianne, Durlach Anne, Grange Florent, Birembaut Philippe, Clavel Christine, Bernard Philippe

机构信息

CHU Reims, Hôpital Robert Debré, Service de Dermatologie, Avenue du Général Koenig, Reims F-51092, France.

出版信息

Eur J Dermatol. 2006 Sep-Oct;16(5):518-22.

Abstract

BACKGROUND

Recently, an increased expression of P16, a cell cycle regulatory tumor suppressor protein, has been demonstrated in cervical squamous neoplasms as a marker of malignancy. In contrast, studies performed in skin carcinomas led to contradictory results.

OBJECTIVES

Our first aim was to evaluate P16 expression in different types of non-melanoma skin cancers compared with normal skin and benign tumors. The second aim was to evaluate the relationship between P16 expression and the location of skin tumors (i.e. exposed versus non exposed sites). Finally, we also studied Ki67 expression in skin carcinomas and control biopsies.

METHODS

Skin biopsy specimens with typical histologic features of squamous cell carcinoma (SCC; n = 30), Bowen's disease (BD; n = 17), basal cell carcinoma (BCC; n = 10), seborrheic keratosis (SK; n = 10) and normal human skin (NHS; n = 9) were obtained from 76 patients seen at our institution between 2001 and 2003. In all cases, P16 and Ki67 expression were evaluated by immunohistochemistry and image analysis.

RESULTS

P16 overexpression was observed in 58% of cutaneous carcinomas (SCC: 60%; BD: 58%; BCC: 50%) versus 0% of SK or NHS (0%) (p = 0.006). Ki67 expression in over 5% of tumour cells was observed in 69% of cutaneous carcinomas (SCC: 54%; BD: 76%; BCC: 80%) versus 16% in the group including SK (30%) and NHS (0%) (p = 0.04). Overexpression of P16 was associated with a high rate of Ki67 positive tumour cells in 23/57 malignant skin tumors (40%). Both P16 was associated and Ki-67 were negative in 7/57 cases (12%). Sixty-eight percent of tumors located on sun-exposed areas versus 23% of those located on non sun-exposed areas overexpressed P16 (p = 0.02).

CONCLUSION

Our study demonstrated that the expression of P16 and Ki67 is associated with skin carcinomas. No difference was observed according to histological types of carcinomas, suggesting that P16 and Ki67 expression did not correlate with the degree of proliferation and malignancy. Within cutaneous carcinoma specimens, P16 overexpression was significantly associated with the location on sun-exposed areas, suggesting a possible induction of P16 overexpression by UV radiation.

摘要

背景

最近,细胞周期调节肿瘤抑制蛋白P16在宫颈鳞状肿瘤中的表达增加,已被证明是恶性肿瘤的标志物。相比之下,在皮肤癌中进行的研究得出了相互矛盾的结果。

目的

我们的首要目标是评估不同类型的非黑素瘤皮肤癌中P16的表达,并与正常皮肤和良性肿瘤进行比较。第二个目标是评估P16表达与皮肤肿瘤位置(即暴露部位与非暴露部位)之间的关系。最后,我们还研究了皮肤癌和对照活检组织中Ki67的表达。

方法

从2001年至2003年在我们机构就诊的76例患者中获取具有鳞状细胞癌(SCC;n = 30)、鲍温病(BD;n = 17)、基底细胞癌(BCC;n = 10)、脂溢性角化病(SK;n = 10)和正常人类皮肤(NHS;n = 9)典型组织学特征的皮肤活检标本。在所有病例中,通过免疫组织化学和图像分析评估P16和Ki67的表达。

结果

58%的皮肤癌(SCC:60%;BD:58%;BCC:50%)中观察到P16过表达,而SK或NHS中为0%(0%)(p = 0.006)。69%的皮肤癌(SCC:54%;BD:76%;BCC:80%)中观察到超过5%的肿瘤细胞表达Ki67,而包括SK(30%)和NHS(0%)的组中为16%(p = 0.04)。在23/57例恶性皮肤肿瘤(40%)中,P16过表达与Ki67阳性肿瘤细胞的高比例相关。在57例病例中有7例(12%)P16和Ki-67均为阴性。位于阳光暴露部位的肿瘤中有68%过表达P16,而位于非阳光暴露部位的肿瘤中这一比例为23%(p = 0.02)。

结论

我们的研究表明,P16和Ki67的表达与皮肤癌相关。根据癌的组织学类型未观察到差异,这表明P16和Ki67的表达与增殖程度和恶性程度无关。在皮肤癌标本中,P16过表达与阳光暴露部位显著相关,提示紫外线辐射可能诱导P16过表达。

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