The development of
somatostatin analogs for the treatment of pituitary
Cushing's disease has been based on
somatostatin receptor expression analyses of small cohorts of
pituitary adenomas. Additionally, the classification of
pituitary adenomas has recently changed. To enable progress with this treatment option, we assessed
somatostatin receptors in a large cohort of corticotroph and other
pituitary adenomas according to the new WHO classification of endocrine
tumors.
Paraffin-embedded
tumor samples of 88 corticotroph
pituitary adenomas and 30 nonadenomatous pituitary biopsies were analyzed after processing into tissue microarrays and immunohistochemical staining for
SSTR 1,
SSTR2A, SSTR3, SSTR4, and SSTR5. For comparison, 159 other noncorticotroph
pituitary adenomas were analyzed. SSTR3 expression was higher in
corticotroph adenomas compared to PIT-1-positive, gonadotroph, and nonfunctioning
pituitary adenomas (p < 0.0001, p = 0.0280, and p < 0.0001, respectively). This was also the case for the expression of SSTR5 (p = 0.0003, p < 0.0001, and p < 0.0001, respectively).
SSTR2A expression was higher compared to gonadotroph and nonfunctioning
pituitary adenomas (p = 0.0217 and 0.0126, respectively) while PIT-1-positive
adenomas showed even higher
SSTR2A expression (p < 0.0001).
SSTR2A and SSTR5 were both expressed higher in nonadenomatous pituitary biopsies than in
pituitary adenomas (p = 0.0126 and p = 0.0008, respectively). There are marked expression differences of SSTR1-5 as well as changes in expression in recurrent disease that need to be addressed when looking for other possible substances for the treatment of
Cushing's disease.
SSTR2A, SSTR3, and SSTR5 seem to be most suitable
biomarkers for a targeted
therapy with
somatostatin analogs.