胃分化型肿瘤的肿瘤分化表型及其与肿瘤侵袭和基因改变的关系。
Tumor differentiation phenotype in gastric differentiated-type tumors and its relation to tumor invasion and genetic alterations.
作者信息
Yamazaki Kimiyasu, Tajima Yusuke, Makino Reiko, Nishino Nobukazu, Aoki Shigeo, Kato Masanori, Sakamoto Masaaki, Morohara Koji, Kaetsu Tsutomu, Kusano Mitsuo
机构信息
Department of Surgery, Division of General and Gastroenterological Surgery, Showa University, School of Medicine, Tokyo, Japan.
出版信息
World J Gastroenterol. 2006 Jun 28;12(24):3803-9. doi: 10.3748/wjg.v12.i24.3803.
AIM
To clarify the relations between tumor differentiation phenotype and tumor invasion or genetic alterations in gastric differentiated-type tumors.
METHODS
We examined the tumor differentiation phenotype, the presence of mutations in APC and p53, and the microsatellite instability (MSI) status in 48 gastric adenomas and 171 differentiated-type carcinomas. The tumor differentiation phenotype was determined by examining the expression of human gastric mucin (HGM), MUC6, MUC2 and CD10. The tumors were then classified into gastric- (G-), gastric and intestinal mixed- (GI-), or intestinal- (I-) phenotypes, according to the immunopositivity of the above markers. The presence of mutations in APC and p53 and the MSI status were also investigated in all the tumors.
RESULTS
Gastric adenomas were significantly associated with CD10 expression, I-phenotype tumors and the presence of APC mutations, compared with carcinomas (66.7% vs 25.1%, P < 0.0001; 56.3% vs 14.6%, P < 0.0001; 39.6% vs 14.0%, P < 0.0001, respectively) and inversely associated with expressions of HGM and MUC6 and the presence of p53 mutations (10.4% vs 62.6%, P < 0.0001; 39.6% vs 64.3%, P = 0.003; 2.0% vs 26.3%, P = 0.001, respectively). The frequency of APC mutations was significantly higher in HGM-negative tumors, MUC6-negative tumors, CD10-positive tumors and I-phenotype tumors than in HGM-positive tumors, MUC6-positive tumors, CD10-negative tumors and G-phenotype tumors (32.7% vs 7.1%, P < 0.0001; 27.8% vs 14.0%, P = 0.0182; 37.3% vs 10.4%, P < 0.0001; and 38.5% vs 9.5%, P = 0.0017, respectively). The frequency of MSI was significantly higher in MUC6-positive tumors, CD10-negative tumors and G-phenotype tumors than in MUC6-negative tumors, CD10-positive tumors and I-phenotype tumors (24.8% vs 6.7%, P = 0.0009; 22.2% vs 8.0%, P = 0.0143; and 28.6% vs 9.6%, P = 0.0353, respectively).
CONCLUSION
The tumor differentiation phenotype is closely related to tumor invasion and genetic alterations in gastric differentiated-type tumors.
目的
阐明胃分化型肿瘤中肿瘤分化表型与肿瘤侵袭或基因改变之间的关系。
方法
我们检测了48例胃腺瘤和171例分化型癌的肿瘤分化表型、APC和p53基因突变情况以及微卫星不稳定性（MSI）状态。通过检测人胃黏蛋白（HGM）、MUC6、MUC2和CD10的表达来确定肿瘤分化表型。然后根据上述标志物的免疫阳性情况，将肿瘤分为胃型（G-）、胃和肠混合型（GI-）或肠型（I-）表型。同时还对所有肿瘤的APC和p53基因突变情况以及MSI状态进行了研究。
结果
与癌相比，胃腺瘤与CD10表达、I型表型肿瘤以及APC基因突变显著相关（分别为66.7%对25.1%，P<0.0001；56.3%对14.6%，P<0.0001；39.6%对14.0%，P<0.0001），而与HGM和MUC6的表达以及p53基因突变呈负相关（分别为10.4%对62.6%，P<0.0001；39.6%对64.3%，P = 0.003；2.0%对26.3%，P = 0.001）。HGM阴性肿瘤、MUC6阴性肿瘤、CD10阳性肿瘤和I型表型肿瘤中APC基因突变的频率显著高于HGM阳性肿瘤、MUC6阳性肿瘤、CD10阴性肿瘤和G型表型肿瘤（分别为32.7%对7.1%，P<0.0001；27.8%对14.0%，P = 0.0182；37.3%对10.4%，P<0.0001；38.5%对9.5%，P = 0.0017）。MUC6阳性肿瘤、CD10阴性肿瘤和G型表型肿瘤中MSI的频率显著高于MUC6阴性肿瘤、CD10阳性肿瘤和I型表型肿瘤（分别为24.8%对6.7%，P = 0.0009；22.2%对8.0%，P = 0.0143；28.6%对9.6%，P = 0.0353）。
结论
胃分化型肿瘤的肿瘤分化表型与肿瘤侵袭和基因改变密切相关。
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