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 prognosis. Methods 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. Results 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. Conclusion 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
