Hamid Q A, Corrin B, Dewar A, Hoefler H, Sheppard M N
Department of Pathology, National Heart and Lung Institute, Brompton Hospital, London, U.K.
J Pathol. 1990 Jun;161(2):145-51. doi: 10.1002/path.1711610209.
Production of the growth factor gastrin-releasing peptide (GRP) or human bombesin has been shown to be a feature of neuroendocrine tumours of the lung, particularly small cell carcinoma, and is possibly responsible for the characteristically rapid growth of this tumour. Large cell undifferentiated carcinoma of the lung (LCC) is also characterized by rapid growth and there is increasing evidence that some LCCs exhibit neuroendocrine differentiation. We therefore investigated GRP/bombesin immunoreactivity and the expression of GRP gene in ten LCCs. Histologically, all were composed of large cells with abundant cytoplasm, open nuclei, and prominent nucleoli, and there was no evidence of squamous, glandular, or neuroendocrine differentiation. At the ultrastructural level, most showed squamous or glandular differentiation but none contained neuroendocrine granules. None of the tumours showed immunoreactivity for GRP/bombesin but seven of the ten showed a focal hybridization signal when treated with 32P-labelled GRP cRNA probes, indicating the presence of GRP mRNA. This was confirmed by northern blot analysis. This study shows for the first time that GRP gene is expressed in LCC. The production of GRP may contribute to the aggressive behaviour of LCC.
生长因子胃泌素释放肽（GRP）或人铃蟾肽的产生已被证明是肺神经内分泌肿瘤的一个特征，尤其是小细胞癌，这可能是该肿瘤典型快速生长的原因。肺大细胞未分化癌（LCC）也以快速生长为特征，并且越来越多的证据表明一些LCC表现出神经内分泌分化。因此，我们研究了10例LCC中GRP/铃蟾肽的免疫反应性以及GRP基因的表达。组织学上，所有病例均由具有丰富细胞质、开放核和明显核仁的大细胞组成，没有鳞状、腺性或神经内分泌分化的证据。在超微结构水平上，大多数显示鳞状或腺性分化，但均未含有神经内分泌颗粒。所有肿瘤均未显示GRP/铃蟾肽的免疫反应性，但10例中有7例在用32P标记的GRP cRNA探针处理时显示出局灶性杂交信号，表明存在GRP mRNA。这通过Northern印迹分析得到证实。本研究首次表明GRP基因在LCC中表达。GRP的产生可能导致LCC的侵袭性行为。
