Schmidt Adriana N, Nanney Lillian B, Boyd Alan S, King Lloyd E, Ellis Darrel L
Division of Dermatology, Department of Medicine, Vanderbilt University Medical School, Nashville, TN 37232, USA.
Exp Dermatol. 2006 Dec;15(12):971-80. doi: 10.1111/j.1600-0625.2006.00502.x.
Melanomas rarely occur before puberty, have a higher death rate for males, and tend to be more invasive during pregnancy. Prior to the discovery of a second oestrogen receptor (ERbeta), studies with the initial oestrogen receptor, ERalpha, showed no obvious role for oestrogen in the pathophysiology of benign or malignant melanocytic lesions. To investigate the specific immunostaining patterns of ERalpha and ERbeta, benign nevocytic nevi, dysplastic nevi with mild, moderate and severe cytological atypia, lentigo malignas and melanomas of varying depth (Clark) and thickness (Breslow) were studied. ERbeta but not ERalpha was the predominant oestrogen receptor we found in all types of benign and malignant melanocytic lesions. The most intense ERbeta immunostaining was seen in melanocytes in dysplastic nevi with severe cytological atypia and in lentigo malignas. ERbeta expression levels also correlated with the malignant tumor microenvironment; i.e., melanocytes in proximity with keratinocytes>deeper dermal melanocytes in contact with stroma>minimally invasive melanomas>Clark Level III/IV or thick melanomas (Breslow). Discovery that ERbeta expression varies in relation to the tumor microenvironment and increasing depth of invasion suggests its possible usefulness as a surrogate marker for neoplasia and prognosis in malignant melanoma.
黑色素瘤在青春期前很少发生,男性的死亡率更高,并且在怀孕期间往往更具侵袭性。在发现第二种雌激素受体(ERβ)之前,对最初的雌激素受体ERα进行的研究表明,雌激素在良性或恶性黑素细胞病变的病理生理学中没有明显作用。为了研究ERα和ERβ的特异性免疫染色模式,我们研究了良性痣细胞痣、具有轻度、中度和重度细胞学异型性的发育异常痣、恶性雀斑样痣以及不同深度(克拉克分级)和厚度( Breslow分级)的黑色素瘤。我们发现,在所有类型的良性和恶性黑素细胞病变中,主要的雌激素受体是ERβ而非ERα。在具有严重细胞学异型性的发育异常痣和恶性雀斑样痣的黑素细胞中,观察到最强的ERβ免疫染色。ERβ表达水平也与恶性肿瘤微环境相关;即,与角质形成细胞相邻的黑素细胞>与基质接触的更深层真皮黑素细胞>微侵袭性黑色素瘤>克拉克三级/四级或厚黑色素瘤( Breslow分级)。ERβ表达随肿瘤微环境和侵袭深度增加而变化的发现表明,它可能作为恶性黑色素瘤肿瘤形成和预后的替代标志物。