Maiorano E, Favia G, Pece S, Resta L, Maisonneuve P, Di Fiore P P, Capodiferro S, Urbani U, Viale G
Department of Pathological Anatomy, University of Bari, Italy.
Int J Immunopathol Pharmacol. 2007 Oct-Dec;20(4):779-89. doi: 10.1177/039463200702000414.
The gene numb encodes for a protein (Numb) involved in cell fate decisions in Drosophila, with proposed endocytic and developmental functions in mammalians. The distribution pattern of Numb in human tissues however, has not been fully characterized. We set out to explore the immunohistochemical expression of Numb in normal and neoplastic (28 adenoid cystic and 34 mucoepidermoid carcinomas) salivary glands, and correlated the results with the clinico-pathologic features of the neoplasms. Intense Numb immunoreactivity was detected in normal ductal cells and in a subset of acinar cells. In salivary carcinomas, we detected diffuse and intense Numb immunostaining in 5 adenoid cystic and 8 mucoepidermoid carcinomas. By contrast, the majority of adenoid cystic and mucoepidermoid cancers showed only moderate (14 and 5 cases) or focal staining (9 and 21 cases), respectively. The corresponding expression of Numb mRNA was documented in normal parotid gland and adenoid cystic carcinoma. Numb immunoreactivity was inversely correlated with the histological grade and Ki-67 immunoreactivity of both adenoid cystic and mucoepidermoid carcinomas. In addition, while tumor grade, stage, Ki-67 and Numb immunoreactivity were associated with disease-free survival in univariate analysis, only Numb and Ki-67 immunoreactivities retained independent prognostic significance in multivariate analysis. These data suggest that loss of Numb is implicated in aberrant differentiation programs of salivary gland carcinomas and may serve as a prognostic indicator in patients treated for these neoplasms.
基因numb编码一种蛋白质（Numb），该蛋白质参与果蝇的细胞命运决定，在哺乳动物中具有内吞和发育功能。然而，Numb在人体组织中的分布模式尚未完全明确。我们着手探究Numb在正常和肿瘤性（28例腺样囊性癌和34例黏液表皮样癌）唾液腺中的免疫组化表达，并将结果与肿瘤的临床病理特征相关联。在正常导管细胞和一部分腺泡细胞中检测到强烈的Numb免疫反应性。在唾液腺癌中，我们在5例腺样囊性癌和8例黏液表皮样癌中检测到弥漫性且强烈的Numb免疫染色。相比之下，大多数腺样囊性癌和黏液表皮样癌分别仅显示中度染色（14例和5例）或局灶性染色（9例和21例）。在正常腮腺和腺样囊性癌中记录到了相应的Numb mRNA表达。Numb免疫反应性与腺样囊性癌和黏液表皮样癌的组织学分级及Ki-67免疫反应性呈负相关。此外，在单因素分析中，肿瘤分级、分期、Ki-67和Numb免疫反应性与无病生存期相关，但在多因素分析中，只有Numb和Ki-67免疫反应性保留独立的预后意义。这些数据表明，Numb的缺失与唾液腺癌异常分化程序有关，可能作为这些肿瘤患者的预后指标。
