Skopelitou Antigone S, Mitselou Antigone, Katsanos Konstantinos H, Alexopoulou Vana, Tsianos Epameinondas V
Department of Pathology, Ioannina University Medical School, Greece.
Eur J Gastroenterol Hepatol. 2003 May;15(5):515-23. doi: 10.1097/01.meg.0000059113.41030.67.
Our purpose was to investigate the immunohistochemical expression of Fhit protein in chronic Helicobacter pylori related gastritides, gastric epithelial dysplasia and gastric carcinoma.
Because a subset of chronic H. pylori related gastritides, precancerous lesions and gastric tumours were found to be either entirely negative or to minimally express Fhit protein, it is suggested that alteration of the carcinogen susceptible fragile region within the FHIT gene is an early event in a subset of gastric adenocarcinomas.
We carried out immunohistochemical tests on archived material of formalin fixed, paraffin embedded tissues, using the anti-FHIT antibody and the streptavidin-biotin-peroxidase method, in a total of 135 gastric lesions (76 biopsies and 59 surgically resected gastric adenocarcinomas).
In this study, 79% of H. pylori related gastritides showed that the Fhit protein was either completely absent or there was a marked reduction of immunostaining. Similar results were obtained for 76.4% of cases of chronic gastritides with low and high-grade dysplasia, and 56% of gastric adenocarcinomas. A negative result for Fhit protein immunostaining was strongly associated with H. pylori infection (P = 0.0001) and with epithelial dysplasia (P = 0.01) but not with intestinal metaplasia or degree of activity. Additionally, negative or reduced immunostaining for Fhit was associated with the degree of dysplasia and progress of a subset of these lesions to infiltrating adenocarcinoma (P = 0.02). In gastric adenocarcinomas negative or weak immunostaining of the Fhit protein correlated with the histological grade (P = 0.01) and clinical stage of the disease (P = 0.01).
Our results suggest that, because Fhit protein immunostaining is completely absent in (1) the majority of H. pylori related chronic gastritides, (2) a subset of gastric dysplastic lesions, and (3) a proportion of primary gastric adenocarcinomas, irrespective of histological type, it can play an important role in the early development and progression of some gastric cancers.
我们的目的是研究Fhit蛋白在慢性幽门螺杆菌相关性胃炎、胃上皮发育异常和胃癌中的免疫组化表达。
由于发现一部分慢性幽门螺杆菌相关性胃炎、癌前病变和胃肿瘤要么完全阴性，要么Fhit蛋白表达极低，提示FHIT基因内致癌物敏感脆性区域的改变是一部分胃腺癌的早期事件。
我们使用抗Fhit抗体和链霉亲和素-生物素-过氧化物酶方法，对135例胃病变（76例活检和59例手术切除的胃腺癌）的福尔马林固定、石蜡包埋组织存档材料进行免疫组化检测。
在本研究中，79%的幽门螺杆菌相关性胃炎显示Fhit蛋白完全缺失或免疫染色明显减少。76.4%的低级别和高级别发育异常慢性胃炎病例以及56%的胃癌病例也得到了类似结果。Fhit蛋白免疫染色阴性结果与幽门螺杆菌感染（P = 0.0001）和上皮发育异常（P = 0.01）密切相关，但与肠化生或活动程度无关。此外，Fhit免疫染色阴性或减少与一部分病变的发育异常程度以及这些病变进展为浸润性腺癌相关（P = 0.02）。在胃腺癌中，Fhit蛋白免疫染色阴性或弱阳性与疾病的组织学分级（P = 0.01）和临床分期（P = 0.01）相关。
我们的结果表明，由于Fhit蛋白免疫染色在（1）大多数幽门螺杆菌相关性慢性胃炎、（2）一部分胃发育异常病变以及（3）一部分原发性胃腺癌中完全缺失，无论组织学类型如何，它在一些胃癌的早期发生和进展中可能起重要作用。
