Collins K A, White W L
Department of Pathology, Bowman Gray School of Medicine, Winston-Salem, NC 27157, USA.
Am J Dermatopathol. 1995 Oct;17(5):429-38. doi: 10.1097/00000372-199510000-00001.
The expression of intercellular adhesion molecule 1 (ICAM-1), a molecule pivotal in many inflammatory and immune paracrine interactions, has been highly correlated with malignant melanoma (MM) progression. Because numerous parallels exist between tissues of neural crest origin and the immune system in the regulation of postmitotic cell survival, ICAM-1 expression was studied in MM and compared with that of B-cell lymphoma/leukemia 2 protein (bcl-2 oncoprotein), an important regulator in prolonging lymphoid cell survival by blocking programmed cell death. Frozen sections from 33 cases were studied by immunoperoxidase techniques: 14 primary MM (five in situ), nine metastatic MM (one epidermotropic), four melanocytic nevi, and six normal skin controls. The percentages of the cells that stained and their intensities (0-4+) were graded. Both ICAM-1 (90%, 3-4+) and bcl-2 (95%, 2-4+) were strongly expressed in all nine metastases, including the epidermotropic disease extension. Bcl-2 strongly decorated the tumor cells in all 14 cases of primary MM (80%, 2-4+); in the five in situ MM, bcl-2 stained the atypical melanocytes at the dermal-epidermal junction (DEJ) and throughout the epidermis (75%, 1-2+). In contrast, ICAM-1 was negative in the in situ MM. ICAM-1 expression became strong (85%, 2-4+) in the dermal component of early invasive disease. Both ICAM-1 and bcl-2 were expressed in melanocytic nevi, decreasing in intensity deep within the dermis as the nevus cells senesced ("matured"). Only bcl-2 was expressed in the normal melanocytes of the six skin controls. These data show that bcl-2 is constitutively expressed in normal melanocytes and melanocytic nevi and persists in the transformed cells of early and late MM. ICAM-1 is expressed only after dermal involvement occurs, both in melanocytic nevi and in invasive MM; it persists in metastatic disease. The coexpression of bcl-2 and ICAM-1 demonstrates another similarity between the immune and neural crest systems, but it does not define or necessarily imply any functional interaction between the two proteins. The intercellular relationship of these two molecules, if any, remains to be investigated.
细胞间黏附分子1（ICAM-1）在许多炎症和免疫旁分泌相互作用中起关键作用，其表达与恶性黑色素瘤（MM）进展高度相关。由于神经嵴起源的组织与免疫系统在有丝分裂后细胞存活调节方面存在许多相似之处，因此对MM中的ICAM-1表达进行了研究，并与B细胞淋巴瘤/白血病2蛋白（bcl-2癌蛋白）进行了比较，bcl-2癌蛋白是通过阻断程序性细胞死亡来延长淋巴细胞存活的重要调节因子。采用免疫过氧化物酶技术对33例患者的冰冻切片进行研究：14例原发性MM（5例原位癌）、9例转移性MM（1例亲表皮性）、4例黑素细胞痣和6例正常皮肤对照。对染色细胞的百分比及其强度（0-4+）进行分级。在所有9例转移灶中，包括亲表皮性疾病扩展灶，ICAM-1（90%，3-4+）和bcl-2（95%，2-4+）均强烈表达。在所有14例原发性MM中，bcl-2均强烈标记肿瘤细胞（80%，2-4+）；在5例原位MM中，bcl-2在真皮-表皮交界处（DEJ）和整个表皮的非典型黑素细胞中染色（75%，1-2+）。相比之下，原位MM中的ICAM-1为阴性。在早期浸润性疾病的真皮成分中，ICAM-1表达变强（85%，2-4+）。ICAM-1和bcl-2在黑素细胞痣中均有表达，随着痣细胞衰老（“成熟”），在真皮深层强度降低。在6例皮肤对照的正常黑素细胞中仅表达bcl-2。这些数据表明，bcl-2在正常黑素细胞和黑素细胞痣中组成性表达，并在早期和晚期MM的转化细胞中持续存在。ICAM-1仅在黑素细胞痣和浸润性MM发生真皮受累后表达；它在转移性疾病中持续存在。bcl-2和ICAM-1的共表达证明了免疫和神经嵴系统之间的另一个相似之处，但并未定义或必然暗示这两种蛋白之间存在任何功能相互作用。这两种分子的细胞间关系（如果存在的话）仍有待研究。
