MACC1, a Potential Diagnostic Marker for Early Stage Colorectal Cancer
Bing Ren, Vladislav Zakharov, Charlotte Ryan, Loralee McMahon, Qi Yang, Wenqing Cao. University of Rochester Medical Center, Rochester, NY
Background: Metastasis-Associated in Colon Cancer 1 (MACC1), a newly identified gene, may act as a key regulator of the HGF-MET pathway, and is associated with both malignant and metastasis of colorectal carcinoma (CRC). To explore potential markers for early detecting malignancy and predicting metastasis of CRC, we evaluate the expression of MACC1 and MET in adenoma, adenoma with high grade dysplasia, malignant polyps and adenocarcinoma with metastasis.
Design: A total of 48 cases were analyzed, including 13 tubular adenomas, 11 adenomas with high grade dysplasia, 19 malignant polyps (15 intramucosal, 4 invasive adenocarcinoma), and 5 adenocarcinomas with distant metastasis. MACC1 and MET expression were investigated by immunohistochemical method. Cytoplasmic staining for each protein was semiquantified as negative (0), positive with low level expression (1) or positive with high level expression (2). The expression of MACC1 and MET in different groups was evaluated and statistically analyzed.
Results: Positive MACC1 staining was seen in 15% of adenoma, 63% of adenoma with high grade dysplasia, 89% of malignant polyps (13 intramucosal and 4 T1 invasive carcinoma) and 100% of invasive carcinoma with metastasis (P<0.01). Furthermore, high level MACC1 expression was observed in all (5/5) of carcinoma with metastasis and 16% (3/19) of malignant polyps, but not in adenoma or adenoma with high grade dysplasia (P<0.01). Although no significant different expression of MET was found among experimental groups, the correlation between MACC1 and MET expression was seen in carcinoma with metastasis. 80% of metastatic carcinoma showed high expression of both MACC1 and MET. On 10 to 53 months follow up, 7 of 19 of patients with malignant polyps had subsequent segment resection, none of the 19 patients with malignent polyps develops distant metastasis.
Conclusions: Our study suggests that MACC1 may be an important indicator for malignant transition from adenoma to high grade dysplasia, and invasive adenocarcinoma. The expression of MACC1 may serve as a marker for early diagnosis of colorectal cancer. High expression of both MACC1 and MET in colorectal adenocarcinoma with metastasis confirmed the essential roles of these two proteins in the process of cancer metastasis. Met expression does not have diagnostic value in early colorectal malignancy.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 74, Tuesday Afternoon