Filippella Mariagiovanna, Galland Françoise, Kujas Michèle, Young Jacques, Faggiano Antongiulio, Lombardi Gaetano, Colao Annamaria, Meduri Geri, Chanson Philippe
Department of Endocrinology and Reproductive Diseases, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, France.
Clin Endocrinol (Oxf). 2006 Oct;65(4):536-43. doi: 10.1111/j.1365-2265.2006.02630.x.
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.
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.
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.
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).
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.
垂体肿瘤转化基因（pttg）在垂体肿瘤发生过程中起核心作用，但PTTG蛋白表达的文献报道较少，其与肿瘤细胞增殖及垂体腺瘤预后的关系尚不清楚。
本研究旨在根据肿瘤组织学类型、侵袭性及持续/复发状态，评估45例人垂体腺瘤中PTTG和Ki-67的免疫组化表达情况。
肿瘤包括37例大腺瘤和8例微腺瘤。20例患者经蝶窦手术后出现疾病持续或复发。16例患者在术后8 - 72个月观察到疾病复发。
正常垂体组织中未检测到PTTG或Ki-67表达。在垂体腺瘤中，分别有89%和98%的样本肿瘤细胞核PTTG和Ki-67呈阳性，且两种蛋白的表达之间存在强相关性（P < 0.001）。通过ROC曲线法，PTTG评分3.3%是区分复发性和非复发性垂体腺瘤的最佳临界值（P < 0.05；敏感性60%；特异性76%）。在随访超过1年的患者中，PTTG（P < 0.01；敏感性77%；特异性71%）和Ki-67（P < 0.05；敏感性85%；特异性64%）的临界值均为2.9%。PTTG和Ki-67的表达均不受肿瘤最大直径、肿瘤分级、年龄、性别或术前药物治疗的影响。PTTG和Ki-67肿瘤评分> 2.9%均确定了一组无复发生存期显著更长的患者亚组（P < 0.01）。多因素分析显示，Ki-67肿瘤评分> 2.9%是垂体肿瘤术后持续/复发的最佳预测指标（χ² = 8.2，P < 0.01）。
PTTG在大约90%的不同组织学类型的垂体肿瘤中表达，但病例之间差异很大。正如预期的那样，PTTG表达与Ki-67平行，且两者均与更具侵袭性的行为相关。然而，当考虑到充分的术后随访时，2.9%的Ki-67临界值被证明是预测这些肿瘤复发潜能的最可靠生物学标志物。
