Nakata Bunzo, Yashiro Masakazu, Nishioka Nobuaki, Aya Makoto, Yamada Shinobu, Takenaka Chiemi, Ohira Masaichi, Ishikawa Tetsuro, Nishino Hiroji, Wakasa Kenichi, Seki Shuichi, Hirakawa Kosei
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Int J Cancer. 2002 Dec 20;102(6):655-9. doi: 10.1002/ijc.10771.
Intraductal papillary-mucinous carcinoma (IPMC) of the pancreas, a new entity of pancreatic cancer with a favorable prognosis, has shown a gradual increase in the number of reported cases. Patients with high-frequency microsatellite instability (MSI-H) tumors have been shown to survive longer than those with low-frequency MSI (MSI-L) or microsatellite stable (MSS) tumors in colorectal and gastric cancer. We investigated whether MSI-H in patients with IPMC can contribute to a good prognosis. The formalin-fixed paraffin-embedded tumors and surrounding normal pancreatic tissues from 10 patients with IPMCs and 16 with intraductal papillary-mucinous adenomas (IPMAs) were provided for DNA extraction after microdissection. Polymerase chain reaction (PCR) was carried out using 8 microsatellite primer marker sets. The mixed PCR samples were analyzed using a genetic analyzer. MSI-H was determined by assessment of microsatellite variations in 3 or more of the 8 tested markers. Immunohistochemical staining of the MSI-responsible proteins hMLH1 and hMSH2 was conducted for both the IPMC and IPMA samples. Ten percent of IPMC harbored MSI-H tumors, whereas no MSI-H tumors were detected in the IPMAs. Thirty percent of IPMC tumors and 25% of IPMA tumors showed MSI-L. All IPMCs and IPMAs showed normal expression of both hMLH1 and hMSH2. MSI-H and loss of hMLH1 and hMSH2 are very rare events in both IPMCs and IPMAs. We conclude that a good prognosis for patients with IPMC is not associated with MSI-H.
胰腺导管内乳头状黏液性癌(IPMC)是一种预后良好的新型胰腺癌,其报告病例数呈逐渐上升趋势。在结直肠癌和胃癌中,高频微卫星不稳定(MSI-H)肿瘤患者的生存期已被证实长于低频微卫星不稳定(MSI-L)或微卫星稳定(MSS)肿瘤患者。我们研究了IPMC患者中的MSI-H是否有助于良好预后。对10例IPMC患者和16例导管内乳头状黏液性腺瘤(IPMA)患者的福尔马林固定石蜡包埋肿瘤及周围正常胰腺组织进行显微切割后提取DNA。使用8个微卫星引物标记组进行聚合酶链反应(PCR)。混合PCR样本用基因分析仪进行分析。通过评估8个检测标记中3个或更多标记的微卫星变异来确定MSI-H。对IPMC和IPMA样本均进行了MSI相关蛋白hMLH1和hMSH2的免疫组化染色。10%的IPMC存在MSI-H肿瘤,而IPMA中未检测到MSI-H肿瘤。30%的IPMC肿瘤和25%的IPMA肿瘤表现为MSI-L。所有IPMC和IPMA均显示hMLH1和hMSH2表达正常。MSI-H以及hMLH1和hMSH2缺失在IPMC和IPMA中均为非常罕见的事件。我们得出结论,IPMC患者的良好预后与MSI-H无关。