Clinical Correlation to E-cadherin and Granulation Patterns in Corticotroph Tumors

Abstract

Corticotroph adenomas, either secretory or silent, are associated with significant disease persistence and/or recurrence. Surgical resection is the first line treatment; however, recurrence rates range from 30 to 60%. Although several clinical parameters (i.e. postoperative cortisol level, tumor invasion) have been reported to predict tumor recurrence, none have high diagnostic accuracy. Granulation pattern classifies corticotroph tumors as densely granulated (DG) or sparsely granulated (SG) types, with the latter usually larger and more aggressively behaving. E-cadherin, a calcium-dependent adhesion molecule strongly expressed in normal pituitary cells, plays a role in epithelial cell behavior, tissue development, and suppresses epithelial-mesenchymal transition. Since loss of E-cadherin expression in sparsely granulated somatotroph pituitary tumors correlates with a more aggressive disease course, we sought to examine correlation between E-cadherin expression and behavior in densely versus sparsely granulated corticotroph tumors. A retrospective chart review of adult patients with corticotroph adenomas, seen at our institution between January 2012 - 2020 yielded 62 patients: 18 (29%) male and 44 female (71%), with median age at diagnosis of 49 years (range 25-82). Inclusion criteria required sufficient tissue for E- cadherin immunostaining (IHC). Microadenomas were identified in 19/62 (31%) patients, and 38/62 (52%) patients had clinical and biochemical findings consistent with excess cortisol secretion. Pre-operative imaging showed that 22/62 (35%) tumors were invasive into surrounding structures. After further classification as to densely granulated (DG) or sparsely granulated (SG) types by ACTH granulation pattern on IHC, 19/56 (34%) adenomas were SG, 37/56 (66%) were DG and 6 were not classified. E-cadherin staining was absent in 7/62 tumors (11%) and diminished in 5/62 (8%) tumors and staining did not correlate with dense versus sparse corticotroph types. Chi-squared analysis found a significant association between tumor size (greater than or less than 1cm) and secretion, with hormonally active more likely tumors to be microadenomas (p=0.004). Microadenomas were exclusively DG tumors (p<0.001). Further analysis did not find correlation between presence or absence of E-cadherin expression and tumor invasion into adjacent structures, or recurrence. In summary, the data suggests that, unlike somatotroph corticotroph adenomas for recurrence or invasion, nor does it correlate strongly with granulation status.