Koelzer Viktor H, Herrmann Pia, Zlobec Inti, Karamitopoulou Eva, Lugli Alessandro, Stein Ulrike
Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstrasse 31, Bern, CH-3010, Switzerland.
Clinical Pathology Division, Institute of Pathology, University of Bern, Murtenstrasse 31, Bern, CH-3010, Switzerland.
BMC Cancer. 2015 Mar 21;15:160. doi: 10.1186/s12885-015-1150-z.
Metastasis of colorectal cancer (CRC) is directly linked to patient survival. We previously identified the novel gene Metastasis Associated in Colon Cancer 1 (MACC1) in CRC and demonstrated its importance as metastasis inducer and prognostic biomarker. Here, we investigate the geographic expression pattern of MACC1 in colorectal adenocarcinoma and tumor buds in correlation with clinicopathological and molecular features for improvement of survival prognosis.
We performed geographic MACC1 expression analysis in tumor center, invasive front and tumor buds on whole tissue sections of 187 well-characterized CRCs by immunohistochemistry. MACC1 expression in each geographic zone was analyzed with Mismatch repair (MMR)-status, BRAF/KRAS-mutations and CpG-island methylation.
MACC1 was significantly overexpressed in tumor tissue as compared to normal mucosa (p < 0.001). Within colorectal adenocarcinomas, a significant increase of MACC1 from tumor center to front (p = 0.0012) was detected. MACC1 was highly overexpressed in 55% tumor budding cells. Independent of geographic location, MACC1 predicted advanced pT and pN-stages, high grade tumor budding, venous and lymphatic invasion (p < 0.05). High MACC1 expression at the invasive front was decisive for prediction of metastasis (p = 0.0223) and poor survival (p = 0.0217). The geographic pattern of MACC1 did not correlate with MMR-status, BRAF/KRAS-mutations or CpG-island methylation.
MACC1 is differentially expressed in CRC. At the invasive front, MACC1 expression predicts best aggressive clinicopathological features, tumor budding, metastasis formation and poor survival outcome.
结直肠癌（CRC）转移与患者生存率直接相关。我们之前在CRC中鉴定出了新基因结肠癌转移相关基因1（MACC1），并证明了其作为转移诱导因子和预后生物标志物的重要性。在此，我们研究了MACC1在结直肠腺癌和肿瘤芽中的地理表达模式，并将其与临床病理和分子特征相关联，以改善生存预后。
我们通过免疫组织化学对187例特征明确的CRC全组织切片的肿瘤中心、浸润前沿和肿瘤芽进行了MACC1的地理表达分析。分析了每个地理区域中MACC1的表达与错配修复（MMR）状态、BRAF/KRAS突变和CpG岛甲基化的关系。
与正常黏膜相比，MACC1在肿瘤组织中显著过表达（p < 0.001）。在结直肠腺癌中，检测到MACC1从肿瘤中心到前沿显著增加（p = 0.0012）。55%的肿瘤芽细胞中MACC1高度过表达。独立于地理位置，MACC1可预测晚期pT和pN分期、高级别肿瘤芽、静脉和淋巴浸润（p < 0.05）。浸润前沿的高MACC1表达对转移预测（p =
0.0223）和不良生存（p = 0.0217）起决定性作用。MACC1的地理模式与MMR状态、BRAF/KRAS突变或CpG岛甲基化无关。
MACC1在CRC中差异表达。在浸润前沿，MACC1表达最能预测侵袭性临床病理特征、肿瘤芽、转移形成和不良生存结果。
