Fromont-Hankard Gaelle, Philippe-Chomette Pascale, Delezoide Anne-Lise, Nessmann Catherine, Aigrain Yves, Peuchmaur Michel
Service d'Anatomie Pathologique, Hôpital Robert Debré, Paris, France.
Arch Pathol Lab Med. 2002 Apr;126(4):432-6. doi: 10.5858/2002-126-0432-GCDNFE.
It has been recently suggested that dysregulation of developmental factors and disruption of cell turnover could play a role in the pathogenesis of congenital cystic adenomatoid malformation of the lung (CCAM). The glial cell-derived neurotrophic factor (GDNF) is a growth factor involved in organogenesis, and the temporal pattern of GDNF expression suggests that this factor may play a role in lung development.
We studied GDNF expression by immunohistochemistry in postnatally resected CCAM of the lung (n = 10), normal fetal lung (n = 5), and normal postnatal lung (n = 5). We also studied the association between GDNF expression and both cell proliferation and apoptosis.
GDNF was expressed in both epithelial and endothelial compartments of normal fetal lung, whereas no expression was found in normal postnatal lung. In contrast, in CCAM tissue, there was strong GDNF immunostaining that was restricted to epithelial cells. The percentage of proliferating epithelial cells was higher in CCAM tissue than in normal postnatal lung (6.3% vs 1.7%, P <.005). Apoptotic bodies were found in the mesenchyme of both normal fetal lung and CCAM tissue, whereas virtually no apoptotic bodies were detected in normal postnatal lung.
Abnormal GDNF expression in CCAM suggests a dysregulation of the GDNF signaling pathway and argues in favor of a focal arrest in maturation during development. GDNF expression in lung tissue seems to be correlated with cell proliferation, suggesting that this factor could play a role in the growth of both fetal lung and CCAM.
最近有人提出，发育因子失调和细胞更新破坏可能在肺先天性囊性腺瘤样畸形（CCAM）的发病机制中起作用。胶质细胞源性神经营养因子（GDNF）是一种参与器官发生的生长因子，GDNF表达的时间模式表明该因子可能在肺发育中起作用。
我们通过免疫组织化学研究了出生后切除的肺CCAM（n = 10）、正常胎儿肺（n = 5）和正常出生后肺（n = 5）中GDNF的表达。我们还研究了GDNF表达与细胞增殖和凋亡之间的关系。
GDNF在正常胎儿肺的上皮和内皮区室中均有表达，而在正常出生后肺中未发现表达。相比之下，在CCAM组织中，有强烈的GDNF免疫染色，且仅限于上皮细胞。CCAM组织中增殖上皮细胞的百分比高于正常出生后肺（6.3%对1.7%，P <.005）。在正常胎儿肺和CCAM组织的间充质中均发现凋亡小体，而在正常出生后肺中几乎未检测到凋亡小体。
CCAM中GDNF表达异常提示GDNF信号通路失调，并支持发育过程中成熟的局灶性停滞。肺组织中GDNF的表达似乎与细胞增殖相关，表明该因子可能在胎儿肺和CCAM的生长中起作用。
