Pelosi G, Fraggetta F, Pasini F, Maisonneuve P, Sonzogni A, Iannucci A, Terzi A, Bresaola E, Valduga F, Lupo C, Viale G
Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan School of Medicine, Milan, Italy.
Am J Surg Pathol. 2001 Mar;25(3):363-72. doi: 10.1097/00000478-200103000-00011.
Thyroid transcription factor-1 (TTF-1) is a nuclear protein regulating the transcriptional activity of lung-specific genes in the normal and neoplastic bronchioloalveolar cells. It has been implicated in the normal growth and development of the lung, and the disruption of the TTF-1 locus leads to neonatal death with pulmonary hypoplasia. We evaluated retrospectively the prevalence and clinical significance of TTF-1 immunoreactivity in 222 patients with stage I non-small cell lung carcinoma (NSCLC) with a follow-up time of at least 5 years, and we investigated its relationship with other markers of tumor growth, namely cell proliferation and angiogenesis. TTF-1 immunoreactivity was documented by using the commercially available monoclonal antibody 8G7G3/1 in 72% of 97 adenocarcinomas, 5% of 119 squamous cell carcinomas, and in the glandular component of two adenosquamous carcinomas. Four large cell carcinomas were completely unreactive. In adenocarcinomas, but not squamous cell carcinomas, TTF-1 immunoreactivity correlated significantly with microvessel density (p = 0.04) and inversely with the tumor proliferation fraction assessed by Ki-67 immunostaining (p = 0.03). Also, TTF-1-immunoreactive adenocarcinomas showed a trend for a size less than 3 cm (p = 0.08). TTF-1 expression was not related to specific growth patterns, tumor grade, or tumor cell typing. TTF-1 immunoreactivity did not significantly affect patient survival, although patients with more than 75% immunoreactive neoplastic cells showed a trend for longer overall and disease-free survival. Our findings suggest that TTF-1 could be involved in the development of small pulmonary adenocarcinomas, but it has not prognostic implications in patients with stage I NSCLC.
甲状腺转录因子-1（TTF-1）是一种核蛋白，可调节正常和肿瘤性细支气管肺泡细胞中肺特异性基因的转录活性。它与肺的正常生长和发育有关，TTF-1基因座的破坏会导致新生儿因肺发育不全而死亡。我们回顾性评估了222例I期非小细胞肺癌（NSCLC）患者中TTF-1免疫反应性的患病率及其临床意义，这些患者的随访时间至少为5年，我们还研究了其与肿瘤生长的其他标志物（即细胞增殖和血管生成）之间的关系。使用市售单克隆抗体8G7G3/1记录TTF-1免疫反应性，结果显示，在97例腺癌中有72%呈阳性，119例鳞状细胞癌中有5%呈阳性，在2例腺鳞癌的腺性成分中呈阳性。4例大细胞癌完全无反应。在腺癌中，而非鳞状细胞癌中，TTF-1免疫反应性与微血管密度显著相关（p = 0.04），与通过Ki-67免疫染色评估的肿瘤增殖分数呈负相关（p = 0.03）。此外，TTF-1免疫反应性腺癌的大小有小于3 cm的趋势（p = 0.08）。TTF-1表达与特定的生长模式、肿瘤分级或肿瘤细胞类型无关。TTF-1免疫反应性对患者生存无显著影响，尽管肿瘤细胞免疫反应性超过75%的患者总体生存和无病生存有延长的趋势。我们的研究结果表明，TTF-1可能参与小的肺腺癌的发生发展，但对I期NSCLC患者没有预后意义。
