Centro de Investigaciones Endocrinológicas, CEDIE-CONICET. Hospital de Niños Dr. R. Gutierrez, Buenos Aires, Argentina.
Clin Endocrinol (Oxf). 2013 Nov;79(5):623-30. doi: 10.1111/cen.12205. Epub 2013 Apr 13.
Pheochromocytomas and paragangliomas (pheo/pgl) are neuroendocrine tumours derived from chromaffin cells. Although mostly benign, up to 26% of pheo/pgl will undergo malignant transformation. Reliable histological signs to differentiate benign pheo/pgl from malignant tumours are currently lacking. Increased IGF-1R expression has been shown during progression to metastatic phenotypes of several types of cancer.
To analyse the distribution and expression of the IGF-1R in pheo/pgl of different genetic origin and degree of malignancy.
We studied the expression of the IGF-1R protein by immunohistochemistry, in 40 primary tumours from patients with pheo/pgl from different genetic aetiology (11 of 29 metastatic/nonmetastatic diseases).
We found a strong association between increased expression of IGF-1R and malignant behaviour regardless of the age at diagnosis and the genetic aetiology. IGF-1R labelling was mostly weak in primary tumours from patients with nonmetastatic pheo/pgl. Conversely, intense IGF-1R labelling was predominant in cases of pheo/pgl with confirmed metastatic disease. The risk of metastases was 11·7 times higher if tumour IGF-1R labelling was intense independently of age at diagnosis. The probability of remaining free of metastases was higher in patients with pheo/pgl scored weak for IGF-1R at 60 months and more than twofold higher at 120 months of follow-up than in patients with intense IGF-1R labelling in their primary tumours.
Our results strongly suggest that IGF-1R is associated with malignancy in familial pheo/pgl and that IGF-1R expression in the primary tumour might be a useful tool to detect those patients harbouring pheo/pgl who have an increased risk of metastasis.
嗜铬细胞瘤和副神经节瘤（pheo/pgl）是源于嗜铬细胞的神经内分泌肿瘤。虽然大多数为良性，但多达 26%的 pheo/pgl 会发生恶性转化。目前缺乏可靠的组织学标志来区分良性 pheo/pgl 和恶性肿瘤。已有研究表明，在几种癌症向转移性表型进展过程中，IGF-1R 的表达增加。
分析不同遗传起源和恶性程度的 pheo/pgl 中 IGF-1R 的分布和表达。
我们通过免疫组织化学研究了来自不同遗传病因（29 例转移性/非转移性疾病中的 11 例）的 40 例pheo/pgl 患者的 IGF-1R 蛋白表达情况。
我们发现，无论诊断时的年龄和遗传病因如何，IGF-1R 的表达增加与恶性行为之间存在很强的相关性。非转移性 pheo/pgl 患者的原发性肿瘤中 IGF-1R 标记通常较弱。相反，在证实有转移性疾病的 pheo/pgl 病例中，强烈的 IGF-1R 标记占主导地位。如果肿瘤 IGF-1R 标记强烈，即使独立于诊断时的年龄，转移的风险也会增加 11.7 倍。在 60 个月和 120 个月的随访中，IGF-1R 评分弱的 pheo/pgl 患者无转移的可能性分别比原发性肿瘤中 IGF-1R 标记强烈的患者高 2 倍和高 2 倍以上。
我们的研究结果强烈表明，IGF-1R 与家族性 pheo/pgl 的恶性程度有关，原发性肿瘤中 IGF-1R 的表达可能是检测那些具有更高转移风险的 pheo/pgl 患者的有用工具。
