Stojadinovic Alexander, Hoos Axel, Nissan Aviram, Dudas Maria E, Cordon-Cardo Carlos, Shaha Ashok R, Brennan Murray F, Singh Bhuvanesh, Ghossein Ronald A
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Hum Pathol. 2003 Jan;34(1):54-64. doi: 10.1053/hupa.2003.55.
We studied 45 patients with typical and 8 with atypical parathyroid adenomas as well as 20 with parathyroid carcinomas. Clinical, pathological, and molecular analyses were conducted on all adenomas. Clinical data were analyzed for 20, histopathologic slides for 16, and tissue specimens for 8 patients with carcinoma. Molecular expression profiles were investigated by immunohistochemistry (IHC) for Ki-67, p53, mdm2, p21, Bcl-2, cyclin D1, and p27 on paraffin-embedded tissues arrayed on tissue microarrays. Trabecular growth and vascular, capsular, and soft-tissue invasion were characteristic of parathyroid carcinomas but not of typical adenomas. No adenomas recurred. Seventy-four percent of carcinomas recurred, most in the neck. Seventy-nine percent of patients with such illness died of disease after an indolent, multiply recurrent course responsive to repeated resections; the 5-year survival rate was 50%. High Ki-67 proliferative index was seen in 2% of adenomas and 25% of carcinomas, whereas p27 expression was present in 80% of adenomas and 18% of carcinomas. The molecular phenotype, p27(+)Bcl-2(+)Ki-67(-)mdm2(+), was observed in 76%, 29%, and 0% of typical and atypical adenomas and carcinomas, respectively. The complexity of molecular phenotypes increased with tumor aggressiveness. Parathyroid carcinoma is an aggressive disease with a propensity for multiple recurrences. It is characterized by capsular, vascular, and soft-tissue invasion. Recurrence portends poor outcome. Molecular markers, Ki-67 and p27, may distinguish parathyroid carcinoma from adenoma. The molecular phenotype, p27(+)Bcl-2(+)Ki-67(-)mdm2(+), appears to be unique to nonmalignant parathyroid tumors, and multimarker phenotypes are more complex in carcinomas.
我们研究了45例典型甲状旁腺腺瘤患者、8例非典型甲状旁腺腺瘤患者以及20例甲状旁腺癌患者。对所有腺瘤进行了临床、病理和分子分析。对20例患者的临床数据进行了分析，对16例患者的组织病理切片进行了分析，对8例甲状旁腺癌患者的组织标本进行了分析。通过免疫组织化学（IHC）对组织微阵列上的石蜡包埋组织进行Ki-67、p53、mdm2、p21、Bcl-2、细胞周期蛋白D1和p27的分子表达谱研究。小梁状生长以及血管、包膜和软组织侵犯是甲状旁腺癌的特征，但不是典型腺瘤的特征。没有腺瘤复发。74%的癌复发，大多数发生在颈部。79%的此类疾病患者在经过惰性、多次复发且对反复切除有反应的病程后死于疾病；5年生存率为50%。2%的腺瘤和25%的癌出现高Ki-67增殖指数，而80%的腺瘤和18%的癌存在p27表达。分子表型p27(+)Bcl-2(+)Ki-67(-)mdm2(+)分别在76%、29%和0%的典型和非典型腺瘤及癌中观察到。分子表型的复杂性随肿瘤侵袭性增加。甲状旁腺癌是一种侵袭性疾病，有多次复发的倾向。其特征为包膜、血管和软组织侵犯。复发预示预后不良。分子标志物Ki-67和p27可能有助于区分甲状旁腺癌和腺瘤。分子表型p27(+)Bcl-2(+)Ki-67(-)mdm2(+)似乎是非恶性甲状旁腺肿瘤所特有的，多标志物表型在癌中更为复杂。
