In vivo and in vitro expression of somatostatin receptors in two human thymomas with similar clinical presentation and different histological features

Citation
D. Ferone et al., In vivo and in vitro expression of somatostatin receptors in two human thymomas with similar clinical presentation and different histological features, J ENDOC INV, 24(7), 2001, pp. 522-528
Citations number
24
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
ISSN journal
03914097 → ACNP
Volume
24
Issue
7
Year of publication
2001
Pages
522 - 528
Database
ISI
SICI code
0391-4097(200107/08)24:7<522:IVAIVE>2.0.ZU;2-K
Abstract
[In-111-DTPA(0)]octreotide scintigraphy allows the in vivo visualization of several types of SS receptor (SSR)-expressing tumors. Among these, thymoma s have been recently detected. Here we report on 2 patients admitted for my asthenia gravis and radiological evidence of thymic mass. Although these pa tients had similar clinical presentation, in vivo SSR scintigraphy displaye d a difference in the degree of the [In-111-DTPA(0)]octreotide uptake. Cons idering that both thymic masses had comparable volume, [In-111-DTPA(0)]octr eotide level was significantly higher in one of the 2 tumors (tumor/backgro und ratio of 5.7 vs 2.6). The SSR subtype expression pattern was studied in vitro on the surgically resected specimens by ligand binding techniques, q uantitative reverse transcriptase polymerase chain reaction (RT-PCR) and im munohistochemistry. According to the recent World Health Organization class ification, the 2 tumors were classified A and B2 thymomas respectively. In membrane homogenates, we found a higher number of high affinity [I-125-Tyr( 11)]-SS-14 binding sites in the B2 thymomas (23.5 +/-2.5 vs 12.0 +/-0.4 fmo l/mg membrane protein; p<0.05). RT-PCR analysis showed sst(1), sst(2A) and sst(3) mRNA in the 2 thymoma tissues, whereas SS mRNA was detectable only i n the A thymoma. Quantitative evaluation of RT-PCR data showed a comparable expression of the relative amount of sst(2A) mRNA in both tumors, whereas a significant higher expression of sst(3) mRNA in the B2 thymoma. Sst(2A) i mmunoreactivity was localized mainly on the endothelium of intratumoral ves sels, whereas sst(3) was present on either tumoral epithelial cells or norm al reactive thymocytes. The expression of sst(2A) receptors in these tumors is in line with the in vivo visualization by [In-111-DTPA(0)]octreotide, w hich is considered a sst(2)-preferring ligand. However, since radioligand u ptake was significantly higher in the B2 thymoma, which expressed the large st sst(3) mRNA levels, it might be possible that this subtype is involved i n determining the tumor visualization during SSR scintigraphy. Apart from t he affinity of the radioligand for the receptor, also the efficacy of the i nternalization of the radioligand-receptor complex might play a role in rad ioactivity accumulation during in vivo SSR scintigraphy. In fact, although octreotide binds with lower affinity to sst3 receptors, this subtype displa yed the highest amount of agonist-dependent receptor internalization compar ed to the other SSR subtypes. Moreover, sst3 was localized on both tumor ce lls and reactive thymocytes, and these latter cells are characterized by a very active turnover of membrane molecules. Finally, although more cases ne ed to be evaluated, the lack of detection of SS mRNA in the tumor presentin g a more aggressive phenotype (B2 thymoma) might have physiopathological or prognostic significance. (J. Endocrinol. Invest. 24: 522-528, 2001) (C) 20 01, Editrice Kurtis.