缺碘地区甲状腺肿演变模式的探讨

Investigation of Succession Model for Goiter in Iodine Deficiency Area

目的探讨缺碘地区结节性甲状腺肿继发甲状腺功能亢进及甲状腺癌的演变模式。方法从原白求恩医科大学第三临床医院1980年1月至1994年12月期间切除的216例缺碘地区甲状腺肿患者标本中,按Hedley法以流式细胞仪筛选出24例异倍体标本,再将同一部位的石蜡包埋组织块进行增殖细胞核抗原(PCNA)、层黏蛋白(LN)、第Ⅷ因子相关抗原(FⅧ-RAg)及p53免疫组化染色,观察甲状腺滤泡增殖活性、间质变化及血管新生情况。结果 24例异倍体病例PCNA染色,其标记指数(PCNA-LI)与细胞增殖指数(PI)一致,均呈现高值。不规则的非滤泡状实质性结构、小滤泡以及含泡状大滤泡的多层壁中,PCNA阳性细胞丰富。LN染色发现具有强增殖能力PCNA阳性细胞突破基底膜,形成坏死病灶。第Ⅷ因子相关抗原染色与LN染色结果相结合,发现滤泡上皮增殖明显的部位,血管新生与间质增殖也加剧,为上皮细胞的增殖提供营养和优越的环境。结论甲状腺滤泡上皮增殖、间质增生及血管新生均参与结节形成及甲状腺功能亢进的发生,相应区域应视为癌前病变,提示了缺碘地区甲状腺肿的演变模式。

Objective To investigate the succession model for hyperthyroidism and thyroid carcinoma secondary to nodular goiter in iodine deficiency area.Methods A total of 216 specimens of goiter patients from iodine deficiency area were collected in the former 3rd hospital of Norman Bethune Medical College from January 1980 to December 1994.Twenty-four heteroploid samples were selected by the method of Hedley with Flow cytometry（FCM） analysis.Paraffin-embedded tissues from the same position were used to perform immunohistochemical staining for proliferating cell nuclear antigen（PCNA）,laminin（LN）,factor Ⅷ related antigen（FⅧ-RAg）,and p53.The proliferative activity,stroma change,and angiogenesis were observed.Results PCNA label index（PCNA-LI） and proliferation index（PI） consistent in 24 heteroploid samples with PCNA staining were significantly higher value.PCNA positive cells were mainly distributed over non-follicular parenchymatous structures,small follicles,and multilayered structures with large bubbly follicles.Destroyed basement membrane and necrosis were found by LN staining in PCNA positive position with vigorous reproductive capacity.Combining FⅧ-RAg staining with LN staining,interstitial proliferation and angiogenesis were obvious in follicular epithelial cells with vigorous reproductive capacity,providing nutrition and superior environment for them.Conclusions The reproduction of thyroid follicular epithelial cells,interstitial proliferation,and angiogenesis are all involved in tuberosis and hyperthyroidism,forming precancerous lesion,which suggest the succession model of goiter in iodine deficiency area.