heterogeneity analysis of metastasis associated in colon cancer 1 macc1 for survival prognosis of colorectal cancer patients a retrospective cohort study background 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 prognosismethods we performed geographic macc1 expression analysis in tumor center invasive front and tumor buds on whole tissue sections of 187 wellcharacterized crcs by immunohistochemistry macc1 expression in each geographic zone was analyzed with mismatch repair mmrstatus brafkrasmutations and cpgisland methylationresults macc1 was significantly overexpressed in tumor tissue as compared to normal mucosa p0001 within colorectal adenocarcinomas a significant increase of macc1 from tumor center to front p00012 was detected macc1 was highly overexpressed in 55 tumor budding cells independent of geographic location macc1 predicted advanced pt and pnstages high grade tumor budding venous and lymphatic invasion p005 high macc1 expression at the invasive front was decisive for prediction of metastasis p00223 and poor survival p00217 the geographic pattern of macc1 did not correlate with mmrstatus brafkrasmutations or cpgisland methylationconclusion 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