Takayama Ryoko, Ishiwata Toshiyuki, Ansai Shin-ichi, Yamamoto Tetsushi, Matsuda Yoko, Naito Zenya, Kawana Seiji
*Department of Dermatology; †Department of Pathology; and ‡Department of Integrative Oncological Pathology, Nippon Medical School, Tokyo, Japan.
Am J Dermatopathol. 2013 Dec;35(8):827-32. doi: 10.1097/DAD.0b013e31827c7f31.
Lumican, a member of the small leucine-rich proteoglycan family, regulates the assembly and diameter of collagen fibers in the extracellular matrix of various tissues. Lumican expression correlates with pathological conditions, including skin fragility, corneal opacification, and corneal and cardiac wound healing. Lumican is overexpressed in tumor cells, including in the breast, colorectal, neuroendocrine cell, uterine cervical, and pancreatic cancers. Lumican expression also correlates with the growth and metastasis of various malignancies. For example, lumican expression is lower in the dermis of malignant melanoma cases than in early-stage melanomas. However, the expression patterns and roles of lumican in nonmelanoma skin cancer have not been elucidated. In this study, we used immunohistochemistry and in situ hybridization to examine the expression patterns of lumican in normal skin, Bowen disease, and actinic keratosis. In normal skin, lumican was expressed in the collagen fibers in the dermis, acrosyringium, follicular epithelium, and sebocytes but not in epidermal keratinocytes. In Bowen disease, lumican was expressed in 34 (91.8%) of 37 patients. Notably, all cases of actinic keratosis were negative for lumican. These findings suggest that lumican plays an important role in the pathogenesis of Bowen disease and actinic keratosis and might be useful as an adjunct to the diagnosis for subtypes of 2 diseases: bowenoid actinic keratosis and Bowen disease in sun-exposed areas.
富含亮氨酸小分子蛋白聚糖家族成员之一的核纤层蛋白,可调节多种组织细胞外基质中胶原纤维的组装和直径。核纤层蛋白的表达与包括皮肤脆弱、角膜混浊以及角膜和心脏伤口愈合等病理状况相关。核纤层蛋白在肿瘤细胞中过表达,包括乳腺癌、结直肠癌、神经内分泌细胞癌、子宫颈癌和胰腺癌。核纤层蛋白的表达还与各种恶性肿瘤的生长和转移相关。例如,恶性黑色素瘤病例真皮中的核纤层蛋白表达低于早期黑色素瘤。然而,核纤层蛋白在非黑色素瘤皮肤癌中的表达模式和作用尚未阐明。在本研究中,我们使用免疫组织化学和原位杂交技术检测了核纤层蛋白在正常皮肤、鲍温病和光化性角化病中的表达模式。在正常皮肤中,核纤层蛋白在真皮、顶泌汗腺导管、毛囊上皮和皮脂腺细胞的胶原纤维中表达,但不在表皮角质形成细胞中表达。在鲍温病中,37例患者中有34例(91.8%)表达核纤层蛋白。值得注意的是,所有光化性角化病病例的核纤层蛋白均为阴性。这些发现表明,核纤层蛋白在鲍温病和光化性角化病的发病机制中起重要作用,可能有助于诊断两种疾病的亚型:光化性角化病样鲍温病和暴露部位的鲍温病。