Yoshino Atsuo, Katayama Yoichi, Fukushima Takao, Watanabe Takao, Komine Chiaki, Yokoyama Takakazu, Kusama Kaoru, Moro Itaru
Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
J Neurooncol. 2003 Jun;63(2):155-62. doi: 10.1023/a:1023935621976.
Clinical and histopathological evaluations are inadequate for assessing biological aggressiveness and regrowth potential in benign pituitary adenomas. To develop reliable and prognostically informative means of predicting behavior remains an intractable problem. Telomerase, a reverse transcriptase that extends telomere length, may facilitate tumorigenesis and tumor immortality. In the present study, we investigated the telomerase activity of pituitary adenomas, and attempted to assess the value of telomerase expression for predicting their clinical course. In total, 31 (30 patients) benign pituitary adenoma samples including 8 recurrent adenomas were studied. Telomerase expression was evaluated by polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay and telomerase activity levels were quantitated by improved PCR enzyme-linked immunosorbent assay (ELISA). The data were analyzed in relation to clinical course which was reviewed at 4-5.5 years (median follow-up time, 52.5 months) after surgery. The relative values of the telomerase expression for predicting the clinical course were compared with the MIB-1 antigen-based proliferative cell index (PCI) and p53 immunoreactivity which have recently been suggested to correlate with aggressive behavior in pituitary adenomas. Overall, telomerase expression was detected in 13% of the adenomas (4 tumor tissues, 3 patients). These adenomas comprised large, invasive, and functioning adenomas. The number of telomerase-positive adenomas was small; however, the PCI was higher in cases with telomerase expression (4 tumor tissues; mean, 4.2 +/- 2.4%) than in those without it (27 tumor tissues; 1.4 +/- 1.3%) (p = 0.01). One tumor with detectable telomerase expression, which did not undergo additional pharmacological or radiotherapeutic intervention after first surgery, recurred rapidly despite gross total surgical resection, although the PCI of both the primary and recurrent adenomas was not high. Detection of telomerase expression may represent an additional useful means of identifying aggressive behavior, complementing the histopathological evaluation of benign-appearing pituitary adenomas.
临床和组织病理学评估不足以评估垂体良性腺瘤的生物学侵袭性和再生长潜力。开发可靠且具有预后信息价值的预测行为的方法仍然是一个棘手的问题。端粒酶是一种能延长端粒长度的逆转录酶，可能促进肿瘤发生和肿瘤永生。在本研究中，我们调查了垂体腺瘤的端粒酶活性，并试图评估端粒酶表达对预测其临床病程的价值。总共研究了31个（30例患者）垂体良性腺瘤样本，其中包括8个复发性腺瘤。通过基于聚合酶链反应（PCR）的端粒重复序列扩增法（TRAP）检测端粒酶表达，并通过改进的PCR酶联免疫吸附测定（ELISA）对端粒酶活性水平进行定量。结合术后4至5.5年（中位随访时间，52.5个月）复查的临床病程对数据进行分析。将端粒酶表达预测临床病程的相对值与基于MIB-1抗原的增殖细胞指数（PCI）和p53免疫反应性进行比较，最近有人提出这两者与垂体腺瘤的侵袭性行为相关。总体而言，在13%的腺瘤（4个肿瘤组织，3例患者）中检测到端粒酶表达。这些腺瘤包括大的、侵袭性的和功能性腺瘤。端粒酶阳性的腺瘤数量较少；然而，端粒酶表达阳性的病例（4个肿瘤组织；平均值，4.2±2.4%）的PCI高于无端粒酶表达的病例（27个肿瘤组织；1.4±1.3%）（p = 0.01）。1例检测到端粒酶表达的肿瘤，在首次手术后未接受额外的药物或放射治疗，尽管初次和复发性腺瘤的PCI都不高，但在全切术后仍迅速复发。端粒酶表达的检测可能是识别侵袭性行为的另一种有用方法，可补充外观良性的垂体腺瘤的组织病理学评估。
