CD44 v6基因编码蛋白表达与胃癌转移和预后的关系

Relationship between CD44v6 expression and prognosis in gastric carcinoma patients *

目的观察转移相关粘附分子拼接变异体ＣＤ４４ｖ６在人胃癌组织中的不同表达，探讨ＣＤ４４ｖ６与胃癌病理生物学行为之间的关系，评价ＣＤ４４ｖ６可否作为一个新的客观预测胃癌细胞转移潜能和胃癌患者预后的可靠生物学指标．方法采用鼠抗人ＣＤ４４ｖ６特异性ｍＡｂ，对４５例早期胃癌，２２例中期胃癌和１０３例晚期胃癌手术切除标本之胃原发灶与转移灶进行了ＡＢＣ免疫组化检测．应用χ２检验和Ｌｏｇｒａｎｋ检验方法对结果做统计学分析．结果ＣＤ４４ｖ６在晚期胃癌中的检出率为４６６％（４８／１０３），明显高于早期胃癌（２６７％，１２／４５）和中期胃癌（２７３％，６／２２，Ｐ＜００１）．伴淋巴结转移和伴肝脏转移之胃癌ＣＤ４４ｖ６检出率分别为４９％（５０／１０２）和７１４％（５／７），明显高于不伴转移的胃癌（１８６％，１１／５９，Ｐ＜００１）．肠型胃癌中ＣＤ４４ｖ６检出率为４４９％（４８／１０７），明显高于弥漫型胃癌（２７４％，１７／６２，Ｐ＜００５）．但是，ＣＤ４４ｖ６的表达与胃癌原发灶大小和组织学类型及分化程度未见明显相关．ＣＤ４４ｖ６阳性胃癌患者的术后生存期显著短于ＣＤ４４ｖ６阴性胃癌的患者（Ｐ＝００００２）．结论?

AIM To investigate differential expressions of the human metastasis molecule adhesion CD44 splice variant 6 (CD44v6) in gastric carcinomas (GC), and to evaluate whether CD44v6 can be a useful marker in predicting metastatic potential of GC and prognosis of the patients with GC. METHODS Forty five cases of early gastric carcinoma(EGC), 103 advanced gastric carcinoma(AGC) and 22 intermediate gastric carcinoma(MGC)surgically resected specimens were studied immunohistochemically by using a mAb against CD44v6 (from R&D Systems). An antigen retrieval method followed by a routine ABC Process was employed. RESULTS In the gastric mucosa adjacent to tumour, weak and focal CD44v6 expression was detected within the foveolar proliferation zone but not on mucoid surface epithelium. There was also focally positive reaction in the intestinal metaplasia adjacent to GC. CD44v6 was detected in the membrane of cancer cells in 38 8% (66/170) of GC investigated. CD44v6 was detected in 26 7% (12/45) of EGC, 27 3% (6/22) of MGC, and 46 6% (48/103) of AGC. CD44v6 was detected in 48 2% (53/110) of GC with lymph node metastasis (Ln mets) , 71 4% (5/7) of GC with liver metastasis, while only in 18 6% (11/59) of GC without any metastasis ( P <0 01). Furthermore, CD44v6 was detected in 47 out of 107 (43 9%) intestinal type gastric carcinomas, compared with 17 out of 62 (27 4%)in diffuse type tumours ( P <0 05). The strongly positive reaction to mAb CD44v6 was detected only in GC with Ln mets and liver mets but not in GC without mets ( P <0 05). CD44v6 positive GC patients showed a significantly shorter survival period after surgical operation than those with CD44v6 negative GC patients ( P =0 0002). CONCLUSION The expression of CD44v6 is correlated with progression and metastasis of GC, as well as with worse prognosis of patients with GC. CD44v6 is hopefully to be a useful marker of predicting the metastatic potential of GC and the prognosis of the patients with GC.