Sadler G P, Morgan J M, Jasani B, Douglas-Jones A, Wheeler M H
Department of Surgery, University Hospital of Wales, Heath Park, CF4 4XN Cardiff, U.K.
World J Surg. 1996 Sep;20(7):736-42; discussion 742-3. doi: 10.1007/s002689900112.
The epidermal growth factor receptor (EGFr) family has been increasingly recognized as an important component in the control of normal cell proliferation and the pathogenesis of cancer. We have studied EGFr expression in 104 cases of hyperparathyroidism by immunocytochemistry (ICC) and by in situ hybridization (ISH). Using two different monoclonal antibodies, ICC for EGFr was performed on 66 cryostat sections and 38 wax-embedded parathyroid glands. ISH was performed on 49 of these glands using a cocktail of three anti-sense probes to EGFr mRNA and a nonspecific control probe to human HPV-18 virus. Breast and prostate tumors were employed as positive controls for both ICC and ISH. Controls demonstrated positive EGFr staining. None of the 104 parathyroid glands showed any ICC positivity. ISH displayed positive staining for EGFr mRNA in five of six carcinomas and eight of nine nonrenal hyperplastic glands. Only 3 of 15 adenomas and 3 of 19 renal hyperplastic glands showed positive staining. This difference was statistically significant between adenoma and carcinoma (p < 0.05) and between adenoma and nonrenal hyperplasia (p < 0.01) (Tukey's multiple comparison test). This study demonstrates that EGFr mRNA is present in parathyroid tumors. Expression in carcinoma and nonrenal hyperplasia is significantly different from adenoma and renal hyperplastic glands. In contrast, ICC failed to demonstrate EGFr protein expression. These findings suggest that either receptor numbers are too low to detect by ICC or there is a failure of mRNA translation. More studies are needed to establish whether the EGFr plays a role in the development of parathyroid cancer or hyperplasia.
表皮生长因子受体(EGFr)家族在正常细胞增殖调控及癌症发病机制中的重要作用日益受到认可。我们通过免疫细胞化学(ICC)和原位杂交(ISH)技术,对104例甲状旁腺功能亢进病例中的EGFr表达情况进行了研究。使用两种不同的单克隆抗体,对66个冰冻切片和38个石蜡包埋的甲状旁腺进行了EGFr的ICC检测。对其中49个腺体进行ISH检测,使用了针对EGFr mRNA的三种反义探针混合物以及针对人乳头瘤病毒18型(HPV - 18)的非特异性对照探针。乳腺癌和前列腺肿瘤用作ICC和ISH的阳性对照。对照显示EGFr染色阳性。104个甲状旁腺中无一例显示ICC阳性。ISH检测显示,6例癌中有5例、9例非肾性增生腺体中有8例的EGFr mRNA呈阳性染色。15例腺瘤中仅3例、19例肾性增生腺体中仅3例显示阳性染色。腺瘤与癌之间(p < 0.05)以及腺瘤与非肾性增生之间(p < 0.01)的这种差异具有统计学意义(Tukey多重比较检验)。本研究表明,EGFr mRNA存在于甲状旁腺肿瘤中。癌和非肾性增生中的表达与腺瘤和肾性增生腺体有显著差异。相比之下,ICC未能检测到EGFr蛋白表达。这些发现表明,要么是受体数量太少以至于ICC无法检测到,要么是mRNA翻译失败。需要更多研究来确定EGFr是否在甲状旁腺癌或增生的发生中起作用。