不同胃黏膜病变的细胞增殖变化规律及其意义

Proliferative changes of human gastric mucosa cells in different pathological lesions and their clinical significance

目的 研究胃黏膜不同病变时细胞增殖的变化规律及其意义,寻找有效的生物学指标来预测和早期诊断胃癌。方法 采用免疫组织化学SP法检测了30例慢性浅表性胃炎(CSG)、26例慢性萎缩性胃炎(CAG)、40例肠上皮化生(IM)、22例异型增生(DYS)、22例早期胃癌(EGC)和26例进展期胃癌(AGC)的增殖细胞核抗原(PCNA)、表皮生长因子受体(EGFR)、转化生长因子β受体(TGFβR)Ⅰ和TGFβR Ⅱ的表达。所得数据采用秩和检验及Spearman等级相关分析。结果 相应于CSG、CAG、IM、DYS、EGC和AGC不同的胃黏膜病变,PCNA和EGFR的表达递增(P<0.0001),TGFβR Ⅰ(P=0.007)和TGFβR Ⅱ(P<0.0001)的表达递减。PCNA标记指数在DYS时高于CSG、CAG和IM,低于EGC和AGC,其差异有显著性(P<0.0001);EGFR在IM和DYS时比CSG和CAG明显升高,差异有显著性(P<0.0001);TGFβR Ⅰ在EGC和AGC时明显下降,与CSG相比差异有显著性(P=0.007);TGFβRⅡ在AGC时明显下降,与CSG、CAG、IM、DYS及EGC相比差异有显著性(P<0.13001)。EGFR表达与PCNA的表达呈正相关,TGFβR Ⅰ和TGFβR Ⅱ与PCNA分别呈负相关,TGFβR Ⅰ和TGFβRⅡ呈正相关。结论 不同的胃黏膜病变中,DYS是细胞增殖水平发生变化的关键环节;EGFR的升高和TGFβR的下降可能通过对细胞增生水平的调节促进胃癌的发生。

Objective To investigate the variation of cell proliferation and growth in different pathological lesions of gastric mucosa and to assess the possible roles of expression of epidermal growth factor receptor (EGFR) ,transforming growth factor beta receptor type Ⅰ and type Ⅱ(TGFβRⅠ ,TGFβR Ⅱ) . Methods The proliferating cell nuclear antigen(PCNA) , EGFR, TGFβR Ⅰ and TGFβR Ⅱwere studied in chronic superficial gastritis (CSG, n = 30) , chronic atrophic gastritis (CAG, re =26) , intestinal metaplasia (IM,n=40) , Dysplasia (DYS, n =22) , early gastric cancer (EGG, n =22) , advanced gastric cancer (AGC, n = 26) by immunohistochemical methods and their relations with carcinogenesis were analyzed. Results (1)In different gastric mucosa lesions ( CSG, CAG, IM, DYS, EGC, AGC), there were significantly different expression of PCNA (X2 = 91. 06, P < 0. 0001) , EGFR (X2 = 52. 82, P < 0. 0001) , TGFβRⅠ (X2 = 15. 93, P = 0. 007) and TGFβR Ⅱ (X2 = 40.48, P < 0. 0001) , PCNA and EGFR were increased, TGFβR Ⅰ and TGFβR Ⅱ were decreased. (2) In DYS stage, PCNALI (40.00± 16.34) was higher than in CSG (16.63±10. 52),CAG (16. 92±8. 50)and IM (23.25±18.64) ,but lower than EGC (53. 09 ±13. 51) and AGC (57. 54 ± 16. 88) (P <0.0001);(3) EGFR expression in IM (55.0%) and DYS (72.7%) were higher than in CSG (10.0% ) and CAG (3.8%) (P<0.0001), but no different with EGC (59. 1% )and AGC (73. 1% ). (4) TGFβR Ⅰ expression in EGC (50. 0% )and AGC (30. 8% ) were lower than in CSG (73. 3%) (P=0.007). (5) TGFβR Ⅱexpression in AGC (26. 9% ) was lower than in CSG (83. 3% ) , CAG (82. 8% ) , IM ( 65. 0% ) , DYS (54. 5% ) and EGC (45. 5% ) significantly (P < 0. 0001). (6)The expression of EGFR had positive correlation with PCNA , TGFβR Ⅰ and TGFβR Ⅱhad negative correlation with PCNA respectively, TGFβR Ⅰ and TGFβRⅡ had positive correlation. Conclusions DYS is the key link in the change of cell proliferation during gastric carcinogenesis; The increase of EGFR and the decrease of TGFβR may play important roles in promoting gastric carcinogenesis by affecting gastric cell proliferation.