Brabender J, Lord R V, Danenberg K D, Metzger R, Schneider P M, Park J M, Salonga D, Groshen S, Tsao-Wei D D, DeMeester T R, Hölscher A H, Danenberg P V
Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
J Surg Res. 2001 Aug;99(2):301-6. doi: 10.1006/jsre.2001.6186.
Esophageal adenocarcinoma develops through a multistage process which is characterized histopathologically by progression from Barrett's intestinal metaplasia to Barrett's esophagus with dysplasia and ultimately to adenocarcinoma. The genetic basis of this process is increasingly well understood, but no studies have examined the role of the transcription factor c-myb in this disease.
c-myb mRNA expression levels were measured using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method in specimens of Barrett's intestinal metaplasia (n = 16), adenocarcinoma (n = 22), matching normal squamous esophagus tissues (n = 38), and normal squamous esophagus tissues from patients without Barrett's esophagus or chronic gastroesophageal reflux disease (n = 10).
The median c-myb mRNA expression levels were significantly increased in Barrett's intestinal metaplasia tissues compared to normal esophagus tissues (P = 0.013) and in Barrett's-associated adenocarcinoma tissues compared to normal squamous esophagus tissues (P = 0.001). The c-myb expression levels increased progressively and significantly in histopathologically worse tissue types, with an increase from normal squamous esophagus mucosa to Barrett's intestinal metaplasia, and from Barrett's intestinal metaplasia to adenocarcinoma of the esophagus (P = 0.002). Median c-myb expression levels were also significantly higher in histologically normal squamous esophagus tissues from cancer patients compared to normal esophagus tissues from patients without cancer (P < 0.001) and a control group without evidence of Barrett's esophagus or gastroesophageal reflux disease (P = 0.003). Very high c-myb mRNA expression levels were found only in patients with cancer.
These findings suggest that upregulation of c-myb mRNA expression is an early event in the development of Barrett's esophagus and associated adenocarcinoma, that high c-myb mRNA expression levels may be a clinically useful biomarker for the detection of occult adenocarcinoma, and that a widespread cancer "field" effect is present in the esophagus of patients with Barrett's-associated adenocarcinoma.
食管腺癌通过多阶段过程发展，其组织病理学特征是从巴雷特肠化生进展为不典型增生的巴雷特食管，最终发展为腺癌。这一过程的遗传基础日益为人所知，但尚无研究探讨转录因子c-myb在该疾病中的作用。
采用定量逆转录-聚合酶链反应（RT-PCR）方法，检测巴雷特肠化生标本（n = 16）、腺癌标本（n = 22）、配对的正常鳞状食管组织（n = 38）以及无巴雷特食管或慢性胃食管反流病患者的正常鳞状食管组织（n = 10）中c-myb mRNA的表达水平。
与正常食管组织相比，巴雷特肠化生组织中c-myb mRNA表达水平的中位数显著升高（P = 0.013）；与正常鳞状食管组织相比，巴雷特相关腺癌组织中c-myb mRNA表达水平的中位数也显著升高（P = 0.001）。在组织病理学上更严重的组织类型中，c-myb表达水平逐渐且显著升高，从正常鳞状食管黏膜到巴雷特肠化生，再从巴雷特肠化生到食管腺癌（P = 0.002）。与无癌患者的正常食管组织相比，癌症患者组织学正常的鳞状食管组织中c-myb表达水平的中位数也显著更高（P < 0.001），与无巴雷特食管或胃食管反流病证据的对照组相比也显著更高（P = 0.003）。仅在癌症患者中发现c-myb mRNA表达水平非常高。
这些发现表明，c-myb mRNA表达上调是巴雷特食管及其相关腺癌发生发展的早期事件，高c-myb mRNA表达水平可能是检测隐匿性腺癌的临床有用生物标志物，并且在巴雷特相关腺癌患者的食管中存在广泛的癌“场”效应。
