Tumor infiltrating lymphocytes but not serum pituitary antibodies are associated with poor clinical outcome after surgery in patients with pituitary adenoma
Isabella Lupi1, Luca Manetti1, Patrizio Caturegli2, Michele Menicagli3, Genersoso Bevilacqua3, Fausto Bogazzi1 & Enio Martino1
Serum pituitary antibodies (Pit Abs) and tumor infiltrating lymphocytes (TILs) have been described in a small percentage of pituitary adenomas but their clinical significance remains unknown.
Aim of the study was to assess Pit Abs and TILs prevalence in patients with pituitary adenomas and to determine their influence on the clinical outcome. In this prevalence casecontrol study were enrolled 291 pituitary adenoma cases, (110 non-secreting, 30 ACTH-, 69 GH-, 71 PRL-, and 13 TSH-secreting adenoma; 177 operated and 114 untreated), 409 healthy controls, and 14 autoimmune hypophysitis. Pit Abs were measured using immunofluorescence in all cases and controls (n=714). The presence of TILs was evaluated using CD45 staining in a subset of adenomas surgically treated (n=72).
The main outcome measure of the study was the clinical response of pituitary adenoma following surgery during a mean follow up time of 34 months.
Pit Abs prevalence was higher in adenomas (5.1%) than in healthy subjects (0.7% P=0.002) and lower than in autoimmune hypophysitis patients (57%, P<0.0001). Similarly, TILs prevalence was higher in adenomas than in normal pituitary (P=0.01), and lower than in autoimmune hypophysitis (P<0.0001). No correlation between Pit Abs and TILs was found (P=0.78).
A poor clinical outcome was more common in adenoma patients with TILs (11 of 18, 61%) than in those without (17 of 54, 31%, P=0.026). Multivariate regression analysis identified the presence of TILs as independent prognostic factor for persistence/recurrence of pituitary adenoma.
In conclusion, cell-mediated and humoral pituitary autoimmunity are present in a significant number of patients with pituitary adenoma. Only cell-mediated immunity, however, appears to be predictive of a less favorable clinical outcome in these patients.