Loss of microfibril-associated protein 5 (MFAP5) expression in colon cancer stroma.

MFAP5, a 25-kD microfibril-associated glycoprotein that is involved in elastic microfibril assembly, has been demonstrated to be significantly downregulated in tumor stroma by previous gene expression study. The aim of this study was to confirm the reduced expression of MFAP5 in colonic tumor stroma using immunohistochemistry and to explore the utility of MFAP5 as a marker to facilitate diagnosing an invasive component versus pseudoinvasion in colon polyps. In all 19 colon cancer resection cases evaluated, while there was intact MFAP5 immunoreactivity in the uninvolved normal connective tissue, there was marked reduction of MFAP5 immunoreactivity in the desmoplastic stroma surrounding the invasive component. The difference in MFAP5 expression levels was most pronounced within the tumor, while a more heterogeneous expression pattern was observed at the tumor invasive front. Reduction of MFAP5 staining was also observed in the stroma around mucin pools in 6 out of 9 sections from mucinous adenocarcinomas and in areas with high-grade dysplasia. For the polypectomy cases, intact expression of MFAP5 was seen in the stroma surrounding the displaced adenomatous glands in 9 out of 12 polyps with pseudoinvasion. Loss of expression of MFAP5 was observed in the stroma surrounding small foci of invasive adenocarcinoma in 8 of 10 malignant polyps. MFAP5 is a useful marker that may help distinguish normal connective tissue from stroma within invasive colonic adenocarcinoma. MFAP5 may facilitate the distinction between pseudoinvasion and true invasive cancer in colonic adenomatous polyps with a sensitivity of 80% (confidence interval 44-96%) and a specificity of 75% (confidence interval 43-93%) in this small cohort.