Cytokeratin distribution and functional properties of growth hormone-producing pituitary adenomas

In addition to its structural function, cytokeratin may have other important roles within cells. We have reported that in growth hormone-producing adenomas (GH cell adenomas), two distinct types can be recognized by their cytokeratin distribution patterns (dot-like or perinuclear pattern) and that each type has different clinicopathological and endocrinological properties. To confirm these phenomena in a larger series and to clarify the significance of different cytokeratin distribution patterns, we studied cytokeratin localization in 70 GH cell adenomas from acromegalic patients. Type I adenomas ( 15) almost exclusively (>98%) composed of cells with a prominent, dot-like distribution; type 2 adenomas (36) comprised of cells with perinuclear cytokeratin; and type 3 adenomas (11) comprised of both cell types were separated. The remaining 8 did not exhibit a distinct distribution pattern. By electron microscopic immunocytochemistry for cytokeratin, dot-like distribution corresponded to fibrous bodies, whereas perinuclear distribution represented immune deposition in the perinuclear zone. Immunohistochemistry for GH, prolactin, β-thyrotropin, and α-subunit of glycoprotein hormones revealed a reduced expression of these hormones in type 1 adenomas, compared with types 2 and 3 adenomas. In normal pituitary glands, almost all GH cells showed a perinuclear cytokeratin distribution, and only a few GH cells exhibited a dot-like pattern. These findings suggest that a dot-like cytokeratin distribution in GH cells may be pathological (a change from physiological perinuclear distribution) and that adenomas with such a distribution may reduce endocrine activities as a result of unknown factors.