结直肠癌黏液腺癌具有独特的分子遗传学特征。

Mucinous carcinomas of the colorectum have distinct molecular genetic characteristics.

作者信息

Song Geun Am, Deng Guoren, Bell Ian, Kakar Sanjay, Sleisenger Marvin H, Kim Young S

机构信息

Gastrointestinal Research Laboratory, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA.

出版信息

Int J Oncol. 2005 Mar;26(3):745-50.

PMID:15703832

Abstract

We compared the frequency of CpG island methylation phenotype (CIMP), inactivation of APC, p53 and DCC genes and K-ras and BRAF mutations in 39 mucinous carcinomas (MC) and 34 non-mucinous carcinomas (NMC) of the colorectum with different microsatellite instability (MSI) status. The higher incidence of MSI (36% vs. 18%) was observed in MC compared with NMC. APC inactivation and K-ras mutations occurred more frequently in NMC (APC, 88%, p<0.001; K-ras, 58%, p=0.01) than in MC (APC, 24%; K-ras, 28%) regardless of MSI status. BRAF mutation occurred at a higher frequency in MC (18%, p=0.01) than in NMC (0%). However, with respect to inactivation of p53 and DCC, MSI status did matter and in both NMC and MC, more frequent inactivation of p53 and DCC was observed in MSS tumors than in MSI tumors. MSS tumors of NMC had a higher frequency of p53 (58% by IHC, p=0.03 and 83% by LOH, p=0.02) and DCC inactivation (83%, p=0.02) compared to MSI tumors of NMC (p53, 33% by IHC and 20% by LOH; DCC, 20%). MSS tumors of MC also showed a higher frequency of p53 and DCC inactivation (p53, 45% by IHC, p=0.02 and 53% by LOH, p=0.005; DCC, 82%, p=0.001) compared to MSI tumors of MC (p53, 0% by IHC and 0% for LOH; DCC, 17%). MC showed a higher frequency of CIMP compared with NMC (41% vs. 11%, p=0.01). These results indicate that mucinous carcinomas of the colorectum exhibit distinct molecular genetic characteristics and may arise from distinct pathogenic pathways.

摘要

我们比较了39例结直肠黏液腺癌（MC）和34例非黏液腺癌（NMC）中，不同微卫星不稳定性（MSI）状态下CpG岛甲基化表型（CIMP）、APC、p53和DCC基因失活以及K-ras和BRAF突变的频率。与NMC相比，MC中MSI的发生率更高（36%对18%）。无论MSI状态如何，NMC中APC失活和K-ras突变的发生率均高于MC（APC，88%，p<0.001；K-ras，58%，p=0.01；MC中APC为24%，K-ras为28%）。BRAF突变在MC中的发生率高于NMC（18%，p=0.01对0%）。然而，关于p53和DCC的失活，MSI状态确实有影响，在NMC和MC中MSS肿瘤中p53和DCC失活的频率均高于MSI肿瘤。与NMC的MSI肿瘤相比（p53，免疫组化法为33%，杂合性缺失法为20%；DCC为20%），NMC的MSS肿瘤中p53（免疫组化法为58%，p=0.03，杂合性缺失法为83%，p=0.02）和DCC失活的频率更高（83%，p=0.02）。与MC的MSI肿瘤相比（p53，免疫组化法为0%，杂合性缺失法为0%；DCC为17%），MC的MSS肿瘤中p53和DCC失活的频率也更高（p53，免疫组化法为45%，p=0.02，杂合性缺失法为53%，p=0.005；DCC为82%，p=0.001）。与NMC相比，MC中CIMP的频率更高（41%对11%，p=0.01）。这些结果表明，结直肠黏液腺癌表现出独特的分子遗传特征，并可能源于不同的致病途径。