三叶因子家族在胃癌及癌前病变组织中的表达及其意义

目的探讨三叶因子家族（TFF）在胃癌及癌前病变中的表达及其意义。方法选择经胃镜活检并经病理证实的基本正常或轻度浅表性胃炎患者20例（正常胃黏膜组）、慢性浅表性胃炎伴胃黏膜肠上皮化生患者30例（肠上皮化生组）、慢性萎缩性胃炎伴胃黏膜不典型增生患者24例（不典型增生组）和胃癌患者40例（胃癌组）。采用免疫组化S—P法检测上述受检者的手术标本中TFF1、TFF2和TFF3的表达情况，并分析TFF与胃癌组织学类型、分化程度、浆膜浸润、淋巴结转移及TNM分期等临床病理特征的关系。结果TFF1、TFF2在正常胃黏膜、不典型增生胃黏膜、肠上皮化生胃黏膜及胃癌组织中均有表达，二者表达强度依次呈递减趋势（P〈0．05）；TFF3在正常胃黏膜没有表达，而在肠上皮化生胃黏膜、不典型增生胃黏膜和胃癌组织中均有表达，表达强度依次呈递增趋势（P〈0．05）。在胃癌组织中，TFF1在低分化胃癌中的表达阳性率显著高于中高分化胃癌（73．7％与38．1％，P〈0．05），而TFF2在中高分化胃癌中的表达阳性率显著高于低分化胃癌（90．5％与47．4％，P〈0．01），二者均与胃癌是否发生浆膜浸润、是否有淋巴结转移及TNM分期无关（P〉0．05）；TFF3在有浆膜浸润、伴淋巴结转移和分期较晚（Ⅲ/Ⅳ期）胃癌组织中的表达阳性率分别为91．7％、88．9％和95．0％]显著高于无浆膜浸润及淋巴结转移和Ⅰ／Ⅱ期的胃癌组织（37．5％、46．2％和55．0％，P〈0．01），但与胃癌组织的分化程度无关（P〉0．05）；TFF1、TFF2和TFF3在弥漫型胃癌组织中的表达阳性率分别为75．0％、82．1％和85．7％]显著高于肠型胃癌组织分别为25．0％、41．7％和50．0％]，差异有统计学意义（P〈0．05）。结论TFF1和TFF2在正常胃黏膜-肠上皮化生-不典型增生-胃癌组织中的表达逐渐减少以及TFF3的表达逐渐增多可能在胃癌发生中起重要作用。TFF1和TFF2可能是胃癌抑制因子，其表达减少可能使胃癌恶性程度增加；TFF3可能与胃癌浸润转移有关，其表达增多则预后不良。

Expression of Trefoil Factor Family Members in Gastric Cancer, Precancerous Lesion and Their Significance

Objective To explore the expression and significance of trefoil factor 1 (TFF1) , TFF2 and TFF3 in pre-cancerous condition and gastric cancer. Methods TFF expression was determined by immunohistochemistry in paraffin - embedded samples from the patients including normal gastric mucosa ( 20 specimens) , intestinal metaplasia in gastritic mucosa (30 specimens), displastic gastritic micosa (24 specimens) and gastric cancer (40 specimens). To study the relationship the rela-tionship between TFF and gastric cancer tissues histologic type, differentiation of the tumor, depth of invasion, lymph node me-tastases and pathological stages (International union control cancer public TNM stages). Results TFF1, TFF2 and TFF3 were measured in the normal gastric mucosa, intestinal mataplasia, displasic gastric mucosa and gastric cancer, the level of TFF1 and TFF2 expression had a decreased tendency (P<0.05). TFF3 was absent in normal gastric mucosa, but measured in intestinal mataplasia, displasic gastric mucosa and gastric carcinomas, and the level of that expression had a increasing tendency (P < 0. 05). The positive rates of TFF1 expression in poorly differentiated gastric cancer were higher than those in moderately/well dif-ferentiated type (73.7% vs 38. 1% , P <0. 05) ; the TFF2 expression was predominately in well differentiated type, higher than those in poorly differentiated type (90. 5% vs 47.4% , P <0. 01) ; TFF1 and TFF2 was no correlation to gastric cancer se-rosal invasion, lymph node metastasis and TNM classification (P >0. 05). The positive rate of TFF3 in gastric cancers serosal invasion, lymph node metastasis and at stage Ⅲ/Ⅳ (91. 7% , 88. 9% and 95. 0% ) significantly higher than those without sero-sal invasion and lymph node metastasis and stage Ⅰ /Ⅱ (37. 5% , 46. 2% and 55. 0% , P <0. 01, respectively) , but it was no correlation to gastric cancer differentiated type ( P > 0. 05 ). The expression rate of TFF1, TFF2 and TFF3 in diffuse type (75. 0% , 82. 1% and 85. 7% ) were significantly higher than those intestinal type tumors (25. 0% , 41. 7% and 50. 0% , P < 0. 05, respectively). Conclusion Progressive loss of TFF1 and TFF2, together with the increase of TFF3 is likely to be in-volved in the gastric cancer. TFF1 and TFF2 probable depress gastric cancer, and might be a tumor suppressor factors. TFF3 that might play a role in the course of tumor invasion and metastasis. The patients with TFF3 positive gastric cancers may be poor prognosis.