Ruggeri R M, Villari D, Simone A, Scarfi R, Attard M, Orlandi F, Barresi G, Trimarchi F, Trovato M, Benvenga S
Section of Endocrinology, Clinical/Experimental Department of Medicine and Pharmacology, University of Messina School of Medicine, Messina, Italy.
J Endocrinol Invest. 2002 Dec;25(11):959-66. doi: 10.1007/BF03344068.
Data on the expression of interleukin 6 (IL-6)/interleukin 6 receptor (IL-6R) in thyroid nodules is scarce. Based on our recent data of CD30 ligand (CD30L)/CD30 receptor (CD30) in these nodules and on the knowledge that this signal stimulates IL-6 production in non-thyroid neoplasms, we wanted to evaluate the immunocytochemical expression of these 2 ligand/receptor systems in a large archival series of paraffin-embedded specimens. These specimens included 6 normal thyroids and 130 thyroid nodules. Co-expression of IL-6 and IL-6R in the epithelial (follicular) cells was observed solely in CD30L/CD30 positive nodules: 5/15 (33%) oncocytic adenomas; 6/30 (20%) follicular adenomas which belonged to 2 variants (4/4 microfollicular toxic and 2/2 hyalinizing trabecular); 9/30 (30%) papillary thyroid cancers (PTC), all belonging to the conventional variant. In PTC the proportion of tumor epithelial cells that were IL6 positive was inversely correlated with the pTNM staging (r=-0.549, p=0.01). All 15 follicular cancers (FTC), all 6 anaplastic cancers (ATC) were IL-6/lL-6R negative; 14/15 FTC and 5/6 ATC were CD30L/CD30 negative. In another oncocytic adenoma, another 4 conventional PTC and another 7 non-conventional PTC CD30L/CD30 expression was associated to expression of IL-6 only. IL-6 staining associated to absent expression of CD30L and CD30 was observed in 7 follicular adenomas (all belonging to variants different from toxic and hyalinizing trabecular), 2 oncocytic adenomas, 5 of the 30 colloid nodules and 2 normal thyroids. Of the 6 tumors arising from the parafollicular C cells (medullary thyroid cancer, MTC), all 3 that had metastasized were CD30L/CD30/IL-6 positive and IL-6R negative; only IL-6 expression was lost in both the local and distant metastases. This finding matched the loss of IL-6 expression in one PTC metastasis. All 3 non-metastasized MTC were IL-6/IL-6R negative, and 1/3 was CD30L positive/CD30 negative. We conclude that only in a subset of both benign and malignant thyroid nodules the IL-6/IL-6R signal could be induced by the CD30L/CD30. IL-6 expression is related with aggressiveness in both PTC and MTC. In the normal thyroid tissue, colloid nodules, and another subset of benign and malignant thyroid nodules, IL-6 expression is under control of signals other than CD30L/CD30.
关于白细胞介素6（IL-6）/白细胞介素6受体（IL-6R）在甲状腺结节中表达的数据很少。基于我们最近关于这些结节中CD30配体（CD30L）/CD30受体（CD30）的数据，以及该信号在非甲状腺肿瘤中刺激IL-6产生的知识，我们想在一大系列石蜡包埋标本的存档资料中评估这两种配体/受体系统的免疫细胞化学表达。这些标本包括6个正常甲状腺和130个甲状腺结节。仅在CD30L/CD30阳性结节的上皮（滤泡）细胞中观察到IL-6和IL-6R的共表达：5/15（33%）嗜酸细胞腺瘤；6/30（20%）滤泡性腺瘤，属于2个亚型（4/4微滤泡毒性型和2/2透明变小梁型）；9/30（30%）甲状腺乳头状癌（PTC），均属于传统亚型。在PTC中，IL6阳性的肿瘤上皮细胞比例与pTNM分期呈负相关（r=-0.549，p=0.01）。所有15个滤泡癌（FTC）、所有6个未分化癌（ATC）均为IL-6/IL-6R阴性；14/15 FTC和5/6 ATC为CD30L/CD30阴性。在另一个嗜酸细胞腺瘤、另外4个传统PTC和另外7个非传统PTC中，CD30L/CD30表达仅与IL-6表达相关。在7个滤泡性腺瘤（均属于不同于毒性型和透明变小梁型的亚型）、2个嗜酸细胞腺瘤、30个胶样结节中的5个和2个正常甲状腺中观察到与CD30L和CD30无表达相关的IL-6染色。在6个由滤泡旁C细胞产生的肿瘤（甲状腺髓样癌，MTC）中，所有3个发生转移的均为CD30L/CD30/IL-6阳性且IL-6R阴性；在局部和远处转移灶中均仅丢失IL-6表达。这一发现与一个PTC转移灶中IL-6表达的丢失相符。所有3个未发生转移的MTC均为IL-6/IL-6R阴性，且1/3为CD30L阳性/CD30阴性。我们得出结论，仅在一部分良性和恶性甲状腺结节中，IL-6/IL-6R信号可由CD30L/CD30诱导。IL-6表达与PTC和MTC的侵袭性相关。在正常甲状腺组织、胶样结节以及另一部分良性和恶性甲状腺结节中，IL-6表达受CD30L/CD30以外的信号控制。
