Pituitary tumour transforming gene (PTTG) expression correlates with the proliferative activity and recurrence status of pituitary adenomas: a clinical and immunohistochemical study.
BACKGROUND
The pituitary tumour transforming gene (pttg) plays a central role in pituitary tumorigenesis, but PTTG protein expression is poorly documented and its relationship with tumour cell proliferation and the prognosis of pituitary adenomas is unclear.


OBJECTIVE
The aim of this study was to evaluate the immunohistochemical expression of PTTG and Ki-67 in 45 human pituitary adenomas according to the tumour histotype, aggressiveness and persistence/recurrence status.


METHODS
The tumours comprised 37 macroadenomas and 8 microadenomas. Twenty patients experienced disease persistence or recurrence after transsphenoidal surgery. Disease recurrence was observed in 16 patients, 8-72 months after surgery.


RESULTS
No PTTG or Ki-67 expression was detected in normal pituitary tissue. In pituitary adenomas, tumour nuclei were positive for PTTG and Ki-67 in 89 and 98% of samples, respectively, and there was a strong correlation between the expression of the two proteins (P < 0.001). By the ROC curves method, a PTTG score of 3.3% was the best cut-off for distinguishing between recurrent and nonrecurrent pituitary adenomas (P < 0.05; sensitivity 60%; specificity 76%). A 2.9% cut-off was obtained for both PTTG (P < 0.01; sensitivity 77%; specificity 71%) and Ki-67 (P < 0.05; sensitivity 85%; specificity 64%) among patients with more than 1 year of follow-up. Neither PTTG nor Ki-67 expression was influenced by the maximal tumour diameter, tumour grade, age, gender or presurgical medical treatment. Both PTTG and Ki-67 tumour score > 2.9% identified a subgroup of patients with a significantly higher recurrence-free interval (P < 0.01). By multivariate analysis, a > 2.9% Ki-67 tumour score was the best predictor of pituitary tumour persistence/recurrence after surgery (chi(2) = 8.2, P < 0.01).


CONCLUSIONS
PTTG is expressed in approximately 90% of pituitary tumours of different histotypes but with a high variability from one case to another. As expected, PTTG expression parallels that of Ki-67 and both are correlated to a more aggressive behaviour. However, a 2.9% Ki-67 cut-off proved to be the most reliable biological marker for predicting the recurrence potential of these tumours, when an adequate postsurgical follow-up is considered.
Filippella
Mariagiovanna
M
Department of Endocrinology and Reproductive Diseases, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, France.
Galland
Françoise
F
Kujas
Michèle
M
Young
Jacques
J
Faggiano
Antongiulio
A
Lombardi
Gaetano
G
Colao
Annamaria
A
Meduri
Geri
G
Chanson
Philippe
P
D000236:Adenoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D016009:Chi-Square Distribution; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064249:Securin; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human