Broekaert D, Cornille A, Eto H, Leigh I, Ramaekers F, Van Muijen G, Coucke P, De Bersaques J, Kluyskens P, Gillis E
Laboratory of Physiological Chemistry, Faculty of Medicine, State University of Ghent, Belgium.
Virchows Arch A Pathol Anat Histopathol. 1988;413(1):39-51. doi: 10.1007/BF00844280.
Cytokeratin expression was studied in human middle ear cholesteatoma lesions, using a variety of immunohistological techniques and a wide range of polyclonal antisera and monoclonal antibodies against cytokeratin (CK) subgroups or individual CK polypeptides. The expression of the other cytoskeletal proteins, vimentin and desmin, was also investigated. Middle ear mucosa and epidermal tissues were used as reference tissues. Our investigations also included epithelial structures present in the cholesteatoma perimatrix and in dermal tissues. The results indicate that, compared with epidermal tissues, the expression profile of CKs in cholesteatoma matrix is representative of a hyperproliferative disease. Evaluating the presence of a marker of terminal keratinization - the 56.5 kD acidic CK n degrees 10 - we found supportive evidence of a pronounced retardation of its expression, which did not parallel histological differentiation. In epidermal tissues, the first prickle cell layers are CK10 positive whereas in many cholesteatomas this finding was observed near the stratum granulosum only. Probing the early stages of keratinization - the 58 kD basic CK n degrees 5 and the 50 kD acidic CK n degrees 14 - we regularly observed an extended staining area in the cholesteatoma matrix. In epidermal reference tissues, only the basal and nearest suprabasal layers were convincingly labeled. As a rule, non-epidermal CKs did not belong to the cholesteatoma CK set. However, exceptions to that rule were noticed as a focal or more extended expression of one or more non-epidermal CKs in about half of the cases. Together with the extended CK5 topography, this is further evidence that CK expression is seriously affected by the diseased state. CK expression in the perimatrix is limited to mucous glands, either normal, atrophic or hyperplastic. CKs n degrees 4, 5, 7, 14, 18 and 19, also displayed by middle ear mucosa, were consistently observed. Where ductal arrangements were present, CK10 was also detected, in analogy with the CK10 registration in ductal portions of mucous glands in the external ear canal skin. The absence of CK8 in mucous glands of the perimatrix, however, strongly differentiates these structures from the mucous gland acini and ducti in the external ear canal, where CK8 is systematically expressed. Vimentin staining was restricted to dendritic cells of the matrix (Langerhans cells) and to perimatrix fibroblasts, blood cells and vascular endothelium. Coexpression of CK and vimentin was not observed.
采用多种免疫组织学技术以及多种针对细胞角蛋白（CK）亚群或单个CK多肽的多克隆抗血清和单克隆抗体，对人中耳胆脂瘤病变中的细胞角蛋白表达进行了研究。还研究了其他细胞骨架蛋白波形蛋白和结蛋白的表达。中耳黏膜和表皮组织用作对照组织。我们的研究还包括胆脂瘤基质和真皮组织中存在的上皮结构。结果表明，与表皮组织相比，胆脂瘤基质中CK的表达谱代表了一种增殖性疾病。评估终末角化标记物——56.5kD酸性CK10的存在情况时，我们发现其表达明显延迟的支持性证据，且这种延迟与组织学分化不一致。在表皮组织中，最初的棘细胞层CK10呈阳性，而在许多胆脂瘤中，仅在颗粒层附近观察到这一现象。检测角化早期阶段——58kD碱性CK5和50kD酸性CK14时，我们在胆脂瘤基质中经常观察到染色区域扩大。在表皮对照组织中，只有基底细胞层和最接近的基底上层有明显标记。通常，非表皮CK不属于胆脂瘤CK组。然而，在大约一半的病例中，观察到一种或多种非表皮CK有局灶性或更广泛的表达，这是该规则的例外情况。连同扩展的CK5分布情况，这进一步证明CK表达受到疾病状态的严重影响。基质中的CK表达仅限于黏液腺，这些黏液腺可以是正常的、萎缩的或增生的。始终观察到中耳黏膜也表达的CK4、5、7、14、18和19。在有导管排列的地方，也检测到了CK10，这与外耳道皮肤黏液腺导管部分中CK10的表达情况类似。然而，基质黏液腺中不存在CK8，这使其与外耳道黏液腺腺泡和导管明显不同，外耳道黏液腺中CK8是系统性表达的。波形蛋白染色仅限于基质中的树突状细胞（朗格汉斯细胞）以及基质成纤维细胞、血细胞和血管内皮细胞。未观察到CK和波形蛋白的共表达。
