Tumor infiltrating lymphocytes but not serum pituitary antibodies are associated with poor clinical outcome after surgery in patients with pituitary adenoma.
BACKGROUND
Serum pituitary antibodies (Pit Abs) and tumor-infiltrating lymphocytes (TILs) have been described in pituitary adenomas, but their clinical significance remains unknown.


OBJECTIVE
The objective of the study was to assess Pit Abs and TILs prevalence in pituitary adenomas and their influence on clinical outcome.


METHODS
This was a prevalence case-control study.


METHODS
Two hundred ninety-one pituitary adenoma cases (110 non-secreting, 30 ACTH-69 GH-71 prolactin- and 13 TSH-secreting adenoma; 177 operated and 114 untreated), 409 healthy controls, and 14 autoimmune hypophysitis were enrolled in a tertiary referral center.


METHODS
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).


METHODS
Clinical response of pituitary adenoma after surgery was evaluated.


RESULTS
Pit Abs prevalence was higher in adenomas (5.1%) than healthy subjects (0.7%, P < 0.0001) and lower than in autoimmune hypophysitis patients (57%, P < 0.0001). Similarly, TILs prevalence was higher in adenomas than 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.


CONCLUSIONS
TILs and Pit Abs are present in a significant number of pituitary adenoma patients. Cell-mediated immunity appears to be predictive of a less favorable clinical outcome.
Lupi
Isabella
I
Department of Endocrinology and Metabolism, University of Pisa, 56124 Pisa, Italy.
Manetti
Luca
L
Caturegli
Patrizio
P
Menicagli
Michele
M
Cosottini
Mirco
M
Iannelli
Aldo
A
Acerbi
Giovanni
G
Bevilacqua
Generoso
G
Bogazzi
Fausto
F
Martino
Enio
E
D000236:Adenoma / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000601:surgery*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008297:Male; D010902:Pituitary Gland / Q000276:immunology*; D010911:Pituitary Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000601:surgery*; D011379:Prognosis; D016036:Seroepidemiologic Studies; D016896:Treatment Outcome
D001323:Autoantibodies; D015415:Biomarkers