Piehl M R, Gould V E, Warren W H, Lee I, Radosevich J A, Ma Y X, Rosen S T
Rush-Presbyterian-St. Luke's Medical Center, Department of Pathology, Chicago.
Pathol Res Pract. 1988 Nov;183(6):675-82. doi: 10.1016/s0344-0338(88)80052-9.
Formalin fixed, paraffin embedded sections of 52 cases of pulmonary large cell undifferentiated carcinoma (LCUC) as defined in the current WHO classification were studied immunohistochemically to assess features of exocrine and neuroendocrine (NE) differentiation. Monoclonal antibody 44-3A6 was applied to detect a membrane association protein related to exocrine differentiation. A panel of ten neuroendocrine markers including antibodies to synaptophysin, chromogranin A, serotonin, and seven neuropeptides was used to assess NE differentiation. The broad spectrum anticytokeratin antibody PKK1 was used to confirm the epithelial differentiation of these tumors. Exocrine differentiation was detected in 40/52 (77%) of surgically resected LCUC, despite the absence of recognizable glands by light microscopy. Eighteen of 52 (35%) LCUC exhibited NE differentiation; synaptophysin was the most frequently detected NE marker. Cytokeratin immunostaining with PKK1 was demonstrated in 41/52 (79%) cases. Subsets of LCUC were defined based on their expression of exocrine or NE phenotypic markers. Accordingly, 28/52 (54%) LCUC displayed an exocrine phenotype, 6/52 (12%) a NE phenotype, 12/52 (23%) had combined exocrine and NE phenotypes, and 6/52 (12%) exhibited neither phenotype. In this surgical series, there were no significant differences in stage at presentation for the four subsets. Interestingly, two year survival appeared decreased in patients with tumors displaying the "pure" NE phenotype.
对52例按照当前世界卫生组织分类定义的肺大细胞未分化癌（LCUC）的福尔马林固定、石蜡包埋切片进行免疫组织化学研究，以评估外分泌和神经内分泌（NE）分化特征。应用单克隆抗体44 - 3A6检测与外分泌分化相关的膜相关蛋白。使用一组十种神经内分泌标志物，包括抗突触素、嗜铬粒蛋白A、血清素的抗体以及七种神经肽，来评估NE分化。使用广谱抗细胞角蛋白抗体PKK1来确认这些肿瘤的上皮分化。尽管在光学显微镜下未发现可识别的腺体，但在40/52（77%）的手术切除的LCUC中检测到外分泌分化。52例中的18例（35%）LCUC表现出NE分化；突触素是最常检测到的NE标志物。41/52（79%）的病例中显示了PKK1的细胞角蛋白免疫染色。根据外分泌或NE表型标志物的表达定义了LCUC的亚组。因此，28/52（54%）的LCUC表现出外分泌表型，6/52（12%）表现出NE表型，12/52（23%）具有外分泌和NE联合表型，6/52（12%）既不表现出这两种表型。在这个手术系列中，四个亚组在就诊时的分期没有显著差异。有趣的是，显示“纯”NE表型的肿瘤患者的两年生存率似乎降低了。
