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自身免疫性胰腺炎患者主胰管乳头和胃及结肠黏膜中的 K-ras 突变。

K-ras mutation in the major duodenal papilla and gastric and colonic mucosa in patients with autoimmune pancreatitis.

机构信息

Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.

出版信息

J Gastroenterol. 2010 Jul;45(7):771-8. doi: 10.1007/s00535-010-0211-y. Epub 2010 Feb 16.

Abstract

BACKGROUND

Pancreatic cancer occurs in some patients with autoimmune pancreatitis (AIP). Significant K-ras mutations are frequently detected in the pancreas of AIP patients. AIP may be a pancreatic lesion of IgG4-related systemic disease. Gastric and colonic cancer can occur during the follow up of AIP patients. We examined K-ras mutations in the major duodenal papilla and gastric and colonic mucosa of AIP patients.

METHODS

K-ras analysis and/or immunohistochemical study was performed on the tissues of the major duodenal papilla (n = 8), gastric mucosa (n = 5), colonic mucosa (n = 3), pancreas (n = 5), common bile duct (n = 5), and gallbladder (n = 4) of 12 AIP patients.

RESULTS

Significant K-ras mutations were detected in the major duodenal papilla of 4 of 8 cases [GAT (n = 4)], in the gastric mucosa of 2 of 4 cases [AGT (n = 2)], and in the colonic mucosa of 2 of 3 cases [GAT (n = 2)]. Significant K-ras mutations were detected in the pancreas of all 5 cases [GAT (n = 5), in the common bile duct of 4 cases (GAT (n = 2), TGT (n = 1), and GCT/TGT (n = 1)], and in the gallbladder epithelium of 3 cases [GAT (n = 1), GCT (n = 1), and GTT (n = 1)]. K-ras mutations were detected in the organs associated with IgG4-related fibroinflammation with abundant infiltration of T lymphocytes and forkhead box P3-positive cells.

CONCLUSIONS

Significant K-ras mutations were frequently detected in the major duodenal papilla and gastric and colonic mucosa of AIP patients. AIP patients may have risk factors for gastric and colonic cancer, but the mechanisms of K-ras mutation and its clinical implications are not clear.

摘要

背景

胰腺癌发生于某些自身免疫性胰腺炎(AIP)患者中。在 AIP 患者的胰腺中常检测到显著的 K-ras 突变。AIP 可能是 IgG4 相关系统性疾病的胰腺病变。AIP 患者在随访期间可发生胃癌和结肠癌。我们检查了 AIP 患者的主要十二指肠乳头及胃和结肠黏膜中的 K-ras 突变。

方法

对 12 例 AIP 患者的主要十二指肠乳头(n = 8)、胃黏膜(n = 5)、结肠黏膜(n = 3)、胰腺(n = 5)、胆总管(n = 5)和胆囊(n = 4)的组织进行了 K-ras 分析和/或免疫组织化学研究。

结果

在 8 例中的 4 例(GAT,n = 4)主要十二指肠乳头、4 例中的 2 例(AGT,n = 2)胃黏膜和 3 例中的 2 例(GAT,n = 2)结肠黏膜中检测到显著的 K-ras 突变。在 5 例胰腺(GAT,n = 5)、4 例胆总管(GAT,n = 2,TGT,n = 1,GCT/TGT,n = 1)和 3 例胆囊上皮(GAT,n = 1,GCT,n = 1,GTT,n = 1)中检测到显著的 K-ras 突变。K-ras 突变发生于 IgG4 相关纤维炎症相关器官,伴有大量 T 淋巴细胞和叉头框 P3 阳性细胞浸润。

结论

在 AIP 患者的主要十二指肠乳头和胃及结肠黏膜中经常检测到显著的 K-ras 突变。AIP 患者可能有胃癌和结肠癌的危险因素,但 K-ras 突变的机制及其临床意义尚不清楚。

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