Xie Lining, Hayashida Sayaka, Furue Masutaka
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
J Cutan Pathol. 2011 Jul;38(7):576-80. doi: 10.1111/j.1600-0560.2011.01689.x. Epub 2011 Feb 24.
The Wnt (wingless-type MMTV integration site) gene family encodes secretory signaling molecules that play a diverse biological role in the regulation of normal and pathological processes, including cell growth, differentiation and oncogenesis. However, the role of Wnt genes in the development of extramammary Paget's disease remains unknown.
To investigate the expression of Wnt-1, Wnt-5α and their downstream genes, β-catenin and c-Myc, in extramammary Paget's disease.
Paraffin-embedded specimens of extramammary Paget's disease (33 specimens from 22 patients), including 7 specimens with dermal invasion and 4 with lymph node metastasis, were examined immunohistochemically for Wnt-1, Wnt-5α, β-catenin and c-Myc. Seven normal genital skin specimens served as controls.
The expression levels of Wnt-1 and β-catenin in extramammary Paget's disease were significantly correlated with each other; however, their expression levels in the invasive extramammary Paget's disease were similar to those of wholly intraepithelial extramammary Paget's disease. Nuclear expression of c-Myc was significantly higher in the invasive extramammary Paget's disease in comparison with intraepithelial extramammary Paget's disease. Interestingly, the expression of Wnt-5α in invasive extramammary Paget's disease was significantly downregulated compared to wholly intraepithelial extramammary Paget's disease.
The Wnt-1/β-catenin pathway may not play an important role in the progression of extramammary Paget's disease. The loss of Wnt-5α, however, may play a role in the invasiveness of extramammary Paget's disease.
Wnt（无翅型MMTV整合位点）基因家族编码分泌性信号分子，在正常和病理过程的调节中发挥多种生物学作用，包括细胞生长、分化和肿瘤发生。然而，Wnt基因在乳腺外佩吉特病的发生发展中的作用尚不清楚。
研究Wnt-1、Wnt-5α及其下游基因β-连环蛋白和c-Myc在乳腺外佩吉特病中的表达情况。
采用免疫组织化学方法检测22例患者的33份乳腺外佩吉特病石蜡包埋标本（其中7份有真皮浸润，4份有淋巴结转移）中Wnt-1、Wnt-5α、β-连环蛋白和c-Myc的表达。7份正常生殖器皮肤标本作为对照。
乳腺外佩吉特病中Wnt-1和β-连环蛋白的表达水平显著相关；然而，它们在浸润性乳腺外佩吉特病中的表达水平与完全上皮内乳腺外佩吉特病相似。与上皮内乳腺外佩吉特病相比，浸润性乳腺外佩吉特病中c-Myc的核表达显著升高。有趣的是，与完全上皮内乳腺外佩吉特病相比，浸润性乳腺外佩吉特病中Wnt-5α的表达显著下调。
Wnt-1/β-连环蛋白通路可能在乳腺外佩吉特病的进展中不起重要作用。然而，Wnt-5α的缺失可能在乳腺外佩吉特病的侵袭性中起作用。
