Abstract 553: Can MACC1 plasma transcripts in colon adenoma patients be used as an early indicator of metastasis potential
Authors: Hassan Brim, Pia Hermann, Mehdi Nouraie, Babak Shokrani, Ed Lee, Tahmineh Haidary, Hassan Ashktorab, Ulrik Stein
Journal: Cancer Research (2014)

Abstract Background: Several studies have reported the detection of Metastatic Associated Colon Cancer 1 (MACC1) in colorectal cancer (CRC) patients’ tissues and blood. However the expression of this marker in earlier stages has not been investigated. Aim: To determine MACC1 expression in colonic adenoma, CRC, and blood of African Americans (AA). Materials &amp; Methods: Three tissue microarrays of normal (n=32), adenoma (n=74) and CRC (n=46) tissues from AA patients were constructed. Immunohistochemistry (IHC) using an anti-MACC1 antibody was performed. The stained slides were read by two pathologists who were blinded as to the samples diagnosis. Both staining intensity and percentage were established. The IHC results were analyzed in light of the demographic and pathological characteristics of the patients. Plasma samples from normal (n=45), hyperplastic (HPP; n=15) and tubular adenoma (n=33) patients were tested for MACC1 transcripts. A Mann Whitney Rank Sum Test was used to assess the statistical differences in MACC1 transcripts’ detection. Results: The TMA staining revealed MACC1 expression in all three TMAs including the normals. These normals correspond to adjacent tissues to cancer samples which might explain the MACC1 staining. Male gender showed an increase of MACC1 expression in all three TMA separately or combined (p&amp;lt;0.05). The diagnostic ability of MACC1 was good in the adenoma samples when compared to the normal with an AUC=0.65 (95%CI: 0.55-0.74). The cytoplasmic staining percentage in adenomas had the best combination of sensitivity (0.77) and specificity (0.56). This diagnostic value was less significant in cancer samples (AUC=0.51 (95%CI: 0.43-0.58)). MACC1 transcripts were significantly more expressed in colonic lesions samples when compared to normal patients’ plasma (normal vs. (TA+HPP), p=0.014; normal vs. TA: p=0.011). However, MACC1 transcription in normal vs. HPP samples, was not statically significant (P=0.239). Conclusion: Here we demonstrate that MACC1 is expressed very early in the carcinogenic process since it was detected in adenoma tissue from AA. Its correlation with male gender cannot be explained at this time as there are no epidemiological data that support gender associated metastatic phenotype. MACC1 plasma transcripts reveal that this marker is not only detectable in preneoplastic lesions but also released in patients’ circulation. This finding might be capitalized on to determine colonic lesions with potential metastatic characteristics. [U.S. and H.A. contributed equally to this work.] Citation Format: Hassan Brim, Pia Hermann, Mehdi Nouraie, Babak Shokrani, Ed Lee, Tahmineh Haidary, Hassan Ashktorab, Ulrik Stein. Can MACC1 plasma transcripts in colon adenoma patients be used as an early indicator of metastasis potential. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 553. doi:10.1158/1538-7445.AM2014-553