Pelosi Giuseppe, Leon Maria Elena, Veronesi Giulia, Spaggiari Lorenzo, Pasini Felice, Viale Giuseppe
Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy.
J Thorac Oncol. 2006 Jun;1(5):468-77.
Few data are available on the prevalence and clinicopathological meaning of CD99, the transmembrane product of the pseudoautosomal MIC2 gene, in pulmonary neuroendocrine tumors.
We evaluated CD99 immunoreactivity in lung tissues, pulmonary neuroendocrine hyperplasias, and 136 consecutive pulmonary neuroendocrine tumors of diverse histological types.
By immunohistochemistry, a membranous and/or cytoplasmic immunoreactivity was seen in 60 of 136 (44%) tumors, whereas both normal and hyperplastic neuroendocrine cells of the lung were consistently nonreactive. A steady decrease of the CD99 labeling index was observed from better to poorly differentiated tumors, with a prevalence of the membranous pattern in typical carcinoids (TCs), and of the cytoplasmic pattern in atypical carcinoids (ACs) and large cell neuroendocrine carcinoma/small cell lung carcinoma (P < 0.0001), independent of tumor stage. In TCs/ACs, increased levels of CD99 labeling index or the membranous pattern were associated with low proliferative fraction (P = 0.0011) and smaller tumor size (P = 0.0054) and with lack of regional lymph node metastases (P = 0.0078). Moreover, CD99 expression decreased according to the pN0-2 classes (P = 0.0016), with an inverse relationship between the number of positive lymph nodes, the labeling index (P = 0.013) and the nonmembranous pattern (P = 0.016). At multivariate analysis, both the decreased CD99 labeling index and the negative/cytoplasmic staining were independent risk indicators for lymph node metastases in the subset of TC/AC patients. No relevant relationships were found in large cell neuroendocrine carcinoma/small cell lung carcinoma.
CD99 is especially present in low- to intermediate-grade neuroendocrine tumors of the lung, and loss of the marker correlates with the occurrence of nodal metastases in TC/AC patients.
关于假常染色体MIC2基因的跨膜产物CD99在肺神经内分泌肿瘤中的患病率及临床病理意义的数据较少。
我们评估了肺组织、肺神经内分泌增生以及136例连续的不同组织学类型的肺神经内分泌肿瘤中CD99的免疫反应性。
通过免疫组织化学，在136例肿瘤中的60例（44%）可见膜性和/或细胞质免疫反应性，而肺的正常和增生性神经内分泌细胞始终无反应。从高分化到低分化肿瘤观察到CD99标记指数稳步下降，在典型类癌（TCs）中以膜性模式为主，在非典型类癌（ACs）和大细胞神经内分泌癌/小细胞肺癌中以细胞质模式为主（P < 0.0001），与肿瘤分期无关。在TCs/ACs中，CD99标记指数升高或膜性模式与低增殖分数（P = 0.0011）、较小肿瘤大小（P = 0.0054）以及无区域淋巴结转移（P = 0.0078）相关。此外，CD99表达根据pN0 - 2分级降低（P = 0.0016），阳性淋巴结数量、标记指数（P = 0.013）与非膜性模式（P = 0.016）之间呈负相关。在多变量分析中，CD99标记指数降低和阴性/细胞质染色都是TC/AC患者亚组中淋巴结转移的独立风险指标。在大细胞神经内分泌癌/小细胞肺癌中未发现相关关系。
CD99特别存在于肺的低至中等级别神经内分泌肿瘤中，该标志物的缺失与TC/AC患者淋巴结转移的发生相关。
