Attanoos R L, Webb R, Dojcinov S D, Gibbs A R
Department of Histopathology, Llandough Hospital, Cardiff and Vale NHS Trust, Penarth, Wales, UK.
Histopathology. 2001 Dec;39(6):584-8. doi: 10.1046/j.1365-2559.2001.01295.x.
Malignant epithelioid mesothelioma shows marked cytoarchitectural diversity. The aim of the study was to evaluate how immunoreactivity with mesothelial markers related to histological pattern.
Ninety-two cases of malignant epithelioid mesothelioma (60 pleural, 32 peritoneal) were examined and classified as exhibiting tubulopapillary, adenomatoid, solid, small cell or pleomorphic patterns. All cases were immunohistochemically stained with thrombomodulin, calretinin, CD44H, and cytokeratin 5/6. Cases of malignant mesothelioma exhibited a number of different histological forms. Immunohistochemical expression of each mesothelial marker tested was not homogeneous across different histological patterns of malignant epithelioid mesothelioma, even within the same tumour section. Calretinin (with nuclear expression) was identified to show the highest overall sensitivity and lowest range variation in staining (67% sensitivity in small cell areas to 100% expression in pleomorphic areas). Cytokeratin 5/6 and thrombomodulin yielded similar overall sensitivity. Thrombomodulin appeared to demonstrate higher sensitivity for small cell variant tumour (83% sensitivity). A notable advantage with cytokeratin 5/6 was that expression was more diffuse in nature rather than the focal membranous elaboration seen in thrombomodulin. The widest range of staining was seen in small cell mesothelioma (83% sensitivity with thrombomodulin to 17% sensitivity with cytokeratin 5/6) and in tubulopapillary areas (90% sensitivity with calretinin to 38% sensitivity with CD44H).
Calretinin appears most useful and shows the highest overall sensitivity for malignant epithelioid mesothelioma, with good expression in areas displaying a tubulopapillary, adenomatoid, solid and pleomorphic pattern. For small cell mesothelioma, thrombomodulin appears to confer higher sensitivity and is advocated, in this setting, as the first line mesothelial marker. Cytokeratin 5/6 is a useful and easily interpretable mesothelial marker. CD44H is not of particular use in the diagnosis of malignant epithelioid mesothelioma. Accurate interpretation of immunohistochemistry in mesothelioma requires an awareness of the immunophenotypic heterogeneity identified in different histological forms of the tumour, and this is of particular importance in small biopsies.
恶性上皮样间皮瘤显示出明显的细胞结构多样性。本研究的目的是评估间皮标志物的免疫反应性与组织学模式之间的关系。
对92例恶性上皮样间皮瘤（60例胸膜间皮瘤，32例腹膜间皮瘤）进行检查，并分类为表现为管状乳头状、腺瘤样、实性、小细胞或多形性模式。所有病例均用凝血调节蛋白、钙视网膜蛋白、CD44H和细胞角蛋白5/6进行免疫组织化学染色。恶性间皮瘤病例呈现多种不同的组织学形式。在恶性上皮样间皮瘤的不同组织学模式中，甚至在同一肿瘤切片内，所检测的每种间皮标志物的免疫组织化学表达都不均匀。钙视网膜蛋白（核表达）显示出最高的总体敏感性和最低的染色范围变异（小细胞区域敏感性为67%，多形性区域表达率为100%）。细胞角蛋白5/6和凝血调节蛋白的总体敏感性相似。凝血调节蛋白对小细胞变异型肿瘤似乎显示出更高的敏感性（敏感性为83%）。细胞角蛋白5/6的一个显著优点是其表达在本质上更弥漫，而不是像凝血调节蛋白那样呈局灶性膜状表达。在小细胞间皮瘤（凝血调节蛋白敏感性为83%，细胞角蛋白5/6敏感性为17%）和管状乳头状区域（钙视网膜蛋白敏感性为90%，CD44H敏感性为38%）中观察到最广泛的染色范围。
钙视网膜蛋白似乎最有用，对恶性上皮样间皮瘤显示出最高的总体敏感性，在表现为管状乳头状、腺瘤样、实性和多形性模式的区域有良好表达。对于小细胞间皮瘤，凝血调节蛋白似乎具有更高的敏感性，在这种情况下，被推荐作为一线间皮标志物。细胞角蛋白5/6是一种有用且易于解释的间皮标志物。CD44H在恶性上皮样间皮瘤的诊断中没有特别用途。准确解释间皮瘤的免疫组织化学需要了解在肿瘤不同组织学形式中发现的免疫表型异质性，这在小活检中尤为重要。
