Haugen D R, Akslen L A, Varhaug J E, Lillehaug J R
Department of Biochemistry and Molecular Biology, University of Bergen, Norway.
Int J Cancer. 1993 Aug 19;55(1):37-43. doi: 10.1002/ijc.2910550108.
Autocrine growth stimulation has been identified in several types of human cancer. In the present study we wanted to establish whether autocrine stimulation of the epidermal-growth-factor receptor (EGF-r) by its ligand, transforming growth factor alpha (TGF-alpha) occurs in thyroid neoplasia. We examined 190 fresh, frozen thyroid tissue samples from 70 patients by immunohistochemistry with antibodies to EGF-r, TGF-alpha, c-erbB-2 and c-myc. EGF-r expression was detected in 17 out of 19 papillary carcinomas, TGF-alpha expression in 10, and c-erbB-2 expression in 15. No papillary carcinoma expressed TGF-alpha without also expressing EGF-r. Concomitant expression of EGF-r, TGF-alpha and c-erbB-2 was seen in 7 papillary carcinomas. No EGF-r, TGF-alpha or c-erbB-2 immunopositivity was found in normal-appearing thyroid tissue (25 cases), whereas a few of the non-neoplastic lesions (colloid goitres and diffuse hyperplasias) expressed either EGF-r or TGF-alpha. c-myc expression was detectable in all tissue samples, and expression was invariably nuclear. Increased expression was observed in 10 out of 19 papillary carcinomas, and 8 of these also co-expressed EGF-r and TGF-alpha. In situ hybridization confirmed the presence of TGF-alpha mRNA in tumour epithelium of TGF-alpha-immunopositive samples. The concomitant expression of EGF-r, TGF-alpha and TGF-alpha mRNA gives evidence for a TGF-alpha-EGF-r autocrine loop in thyroid papillary carcinomas. The increased c-myc expression may reflect the proliferative advantage of these tumours.
自分泌生长刺激已在多种人类癌症中得到证实。在本研究中，我们想确定在甲状腺肿瘤中是否存在其配体转化生长因子α（TGF-α）对表皮生长因子受体（EGF-r）的自分泌刺激。我们用针对EGF-r、TGF-α、c-erbB-2和c-myc的抗体，通过免疫组织化学方法检测了70例患者的190份新鲜冷冻甲状腺组织样本。在19例乳头状癌中，17例检测到EGF-r表达，10例检测到TGF-α表达，15例检测到c-erbB-2表达。没有一例乳头状癌在不表达EGF-r的情况下表达TGF-α。7例乳头状癌中同时检测到EGF-r、TGF-α和c-erbB-2的表达。在外观正常的甲状腺组织（25例）中未检测到EGF-r、TGF-α或c-erbB-2免疫阳性，而一些非肿瘤性病变（胶样甲状腺肿和弥漫性增生）表达了EGF-r或TGF-α。在所有组织样本中均检测到c-myc表达，且表达均位于细胞核。在19例乳头状癌中，10例观察到表达增加，其中8例同时还共表达EGF-r和TGF-α。原位杂交证实了TGF-α免疫阳性样本的肿瘤上皮中存在TGF-α mRNA。EGF-r、TGF-α和TGF-α mRNA的同时表达为甲状腺乳头状癌中存在TGF-α-EGF-r自分泌环提供了证据。c-myc表达增加可能反映了这些肿瘤的增殖优势。
