Krunic A L, Garrod D R, Madani S, Buchanan M D, Clark R E
Dermatologic Surgery Unit, Duke University Medical Center, Durham, NC 27710, USA.
Br J Cancer. 1998 Apr;77(8):1275-9. doi: 10.1038/bjc.1998.213.
Desmosomes are intercellular junctions that have been shown to be down-regulated in certain types of carcinoma and that may play a role in suppression of invasion and metastasis. This paper describes an immunohistochemical study of three types of epidermal neoplasms with monoclonal antibody to desmoglein in order to determine how desmosomal staining correlates with the clinical, biological and histopathological features of these neoplasms. Actinic keratosis (AK) is the most common keratinocytic premalignant neoplasm that was reported to have a 10-20% rate of malignant transformation into squamous cell carcinoma (SCC). Keratoacanthoma (KA) is a benign neoplasm that involutes spontaneously after a few months of rapid growth. SCC is a malignant tumour capable of metastasis. Electron microscope studies of KA and SCC showed significantly reduced staining for desmosomes in SCC but not in KA. We have examined staining for desmoglein using the monoclonal antibody 33-3D, a mouse IgM monoclonal antibody, that recognizes the cytoplasmic domains of desmoglein (Dsg)1 and Dsg2 on frozen sections. Immunohistochemical staining of normal skin with this antibody revealed strong pericellular localization of the antigen, outlining the cell membranes of the keratinocytes. A series of 30 AKs, 12 KAs and 24 SCCs was stained immunohistochemically with 33-3D monoclonal antibody. All examined KAs showed extensive pericellular staining for Dsg. By contrast, juxtanuclear staining for Dsg was noted in 12 SCCs, and completely negative staining in seven SCCs. The five remaining SCCs showed focal pericellular staining for the Dsg marker. The most common finding in AK was focal pericellular staining for Dsg, with complete absence of staining in dysplastic areas (25 cases). In five cases negative pericellular staining in dysplastic areas was associated with juxtanuclear accumulation of the Dsg marker. A strong negative correlation between Dsg staining and degree of dysplasia was obtained. The Dsg pattern in KA is similar to normal epidermis and shows a clear difference between KA and SCC. AK has a limited loss of Dsg expression in a SCC-like pattern that is congruent with its premalignant nature. As the stain works on frozen tissue, it may be helpful for rapid differentiation in selected cases in cutaneous oncology and Mohs micrographic surgery. This antibody may also have great potential for the detection of the effects of chemopreventive agents in skin cancer.
桥粒是一种细胞间连接结构，已证实在某些类型的癌症中其表达下调，并且可能在抑制侵袭和转移方面发挥作用。本文描述了一项使用抗桥粒芯糖蛋白单克隆抗体对三种表皮肿瘤进行的免疫组织化学研究，以确定桥粒染色与这些肿瘤的临床、生物学和组织病理学特征之间的相关性。光化性角化病（AK）是最常见的角质形成细胞癌前肿瘤，据报道其恶变成为鳞状细胞癌（SCC）的发生率为10%-20%。角化棘皮瘤（KA）是一种良性肿瘤，在快速生长几个月后会自发消退。SCC是一种能够发生转移的恶性肿瘤。对KA和SCC的电子显微镜研究显示，SCC中桥粒的染色明显减少，而KA中则没有。我们使用单克隆抗体33-3D（一种小鼠IgM单克隆抗体，可识别冷冻切片上桥粒芯糖蛋白（Dsg）1和Dsg2的细胞质结构域）检测了Dsg的染色情况。用该抗体对正常皮肤进行免疫组织化学染色显示，抗原在细胞周围强烈定位，勾勒出角质形成细胞的细胞膜。用33-3D单克隆抗体对30例AK、12例KA和24例SCC进行了免疫组织化学染色。所有检测的KA均显示Dsg在细胞周围广泛染色。相比之下，12例SCC中观察到Dsg在核旁染色，7例SCC中完全阴性染色。其余5例SCC显示Dsg标记物在细胞周围局灶性染色。AK中最常见的发现是Dsg在细胞周围局灶性染色，发育异常区域完全无染色（25例）。在5例中，发育异常区域细胞周围阴性染色与Dsg标记物在核旁积聚有关。Dsg染色与发育异常程度之间存在强烈的负相关。KA中的Dsg模式与正常表皮相似，并且显示出KA和SCC之间的明显差异。AK具有以SCC样模式有限的Dsg表达缺失，这与其癌前性质一致。由于该染色方法适用于冷冻组织，它可能有助于皮肤肿瘤学和莫氏显微外科手术中某些病例的快速鉴别诊断。这种抗体在检测皮肤癌化学预防剂的效果方面也可能具有巨大潜力。
