Reubi J C, Waser B, Khosla S, Kvols L, Goellner J R, Krenning E, Lamberts S
Sandoz Research Institute Berne, Switzerland.
J Clin Endocrinol Metab. 1992 May;74(5):1082-9. doi: 10.1210/jcem.74.5.1349024.
Fifty-one adrenal pheochromocytomas and 14 paragangliomas were evaluated for somatostatin (SRIH) receptor content with in vitro autoradiography on tissue sections from surgically removed tumors, using iodinated 125I[Tyr]3 octreotide as radioligand. Thirty-seven of 51 pheochromocytomas were SRIH receptor positive (73%), as well as 13 of 14 paragangliomas (93%). These SRIH receptors were of high affinity, pharmacologically specific for SRIH and localized on the tumor tissue. Using in vivo imaging techniques with radiolabeled SRIH analogs, paragangliomas could be visualized in five patients, as well as pheochromocytomas in two of three patients. All tumors tested subsequently in vitro (n = 7) were shown to contain SRIH receptors. A majority of pheochromocytomas were also shown to have a high tumoral SRIH content as measured by immunohistochemical techniques. Detection of SRIH messenger RNA in pheochromocytomas by in situ hybridization indicated that the SRIH was produced in the tumors. A weak inverse correlation was observed between SRIH receptor status and tumoral SRIH content, suggesting that SRIH receptors may be down-regulated by high levels of endogenous SRIH in some tumors. There was no correlation between the SRIH receptor status and sex, age, tumor size, benign vs. malignant tumor, or urinary metanephrine excretion. These tumors were also analyzed for allelic losses on various chromosomes and showed significant loss of heterozygosity (LOH) on chromosomes 1p, 3p, 17p, and 22q. All eight tumors with LOH on chromosome 1p were SRIH receptor positive (100%), whereas only 6 of 11 tumors without LOH on 1p (55%) were SRIH receptor positive, suggesting a correlation between LOH on 1p and SRIH receptor positive status. SRIH receptors thus represent a consistent pathobiochemical marker for most of these adrenal and extra-adrenal tumors. In addition, these receptors may be of potential interest for the in vivo localization of these tumors.
采用碘化的125I[酪氨酸]3奥曲肽作为放射性配体，运用体外放射自显影技术，对手术切除肿瘤的组织切片进行检测，评估了51例肾上腺嗜铬细胞瘤和14例副神经节瘤的生长抑素（SRIH）受体含量。51例嗜铬细胞瘤中有37例（73%）为SRIH受体阳性，14例副神经节瘤中有13例（93%）为阳性。这些SRIH受体具有高亲和力，对SRIH具有药理学特异性，且定位于肿瘤组织。运用放射性标记的SRIH类似物进行体内成像技术检测，5例患者的副神经节瘤以及3例患者中2例的嗜铬细胞瘤得以显影。随后对所有体外检测的肿瘤（n = 7）进行检测，结果显示均含有SRIH受体。通过免疫组化技术检测发现，大多数嗜铬细胞瘤还具有较高的肿瘤SRIH含量。通过原位杂交检测嗜铬细胞瘤中的SRIH信使核糖核酸，表明肿瘤中可产生SRIH。观察到SRIH受体状态与肿瘤SRIH含量之间存在微弱的负相关，提示在某些肿瘤中，高水平的内源性SRIH可能会使SRIH受体下调。SRIH受体状态与性别、年龄、肿瘤大小、肿瘤良恶性或尿间甲肾上腺素排泄之间无相关性。还对这些肿瘤的各种染色体上等位基因缺失情况进行了分析，结果显示在1p、3p、17p和22q染色体上存在显著的杂合性缺失（LOH）。1p染色体上存在LOH的所有8例肿瘤均为SRIH受体阳性（100%），而1p染色体上无LOH的11例肿瘤中只有6例（55%）为SRIH受体阳性，提示1p染色体上的LOH与SRIH受体阳性状态之间存在相关性。因此，SRIH受体是大多数这些肾上腺和肾上腺外肿瘤一致的病理生化标志物。此外，这些受体对于这些肿瘤的体内定位可能具有潜在意义。
