The Expression And Its Clinical Significance Of A Disintegrin And Metalloprotease17in Colorectal Adenoma And Cancer

Objective:Primary colorectal cancer (CRC) is one of the most common malignant tumors in China.The incidence has been rising.Despite curarive resection of the primary tumor,40%to50%of the patients ultimately die of metastases.There is an urgent demand for new biological markers that can serve as diognotic and prognostic markers for CRC.A disintegrin and metalloprotease17(ADAM17) is a transmembrane protease which cleaves the ligands of epidermal growth factor(EGFR), such as transforming growth factor-α(TGF-α) and amphiregulin(AR).The soluble and active ligands after cleavage activate EGFR.In the previous studies, ADAM17,ligands and EGFR were shown to play important roles in the development of CRC.The objective of this study is to observe the protein expressions of ADAM17, TGF-α and AR in CRC,colorectal adenoma and adjacent-to-tumor-non-neoplastic mucosa, analyze the relations of the protein expressions of ADAM17、TGF-α and AR and clinico-pathological characteristics of the patients with CRC and adenoma and investigate the possibilities of AD AM17、TGF-α and AR as diagnostic and prognostic biomarkers for CRC and adenoma.Methods:Sixty specimens of CRC after radical resection and forty specimens of colorectal adenomas after colonoscopic resection were collected.There were twenty specimens of adjacent-to-tumor-non-neoplastic mucosa after the radical resection in the control group.The tissue sections were formalin-fixed and paraffin-embedded. ADAM17,TGF-α and AR proteins were respectively detected by immunohistochemistry (IHC).Clinico-pathological characteristics of the patients were recorded.Results:1. ADAM17、TGF-α and AR proteins were mainly expresed in the cytoplasm and membrane. The staining was strong and diffuse with brown granules in CRC. The staining was slightly diffuse with moderately brown granules in adenomas.The staining was weak and patchy with slightly brown granules in adjacent-to-tumor-non-neoplastic mucosa. The staining got stronger gradually in the sequence of adjacent-to-tumor-non-neoplastic mucosa, adenoma and CRC. 2. The positive rates of ADAM17protein expressions were80.0%,55.0%and15.0%respectively and with statistical difference in general.3. The positive rates of TGF-a protein expressions were71.7%,52.5%and20.0%respectively with statistical difference in general.4. The positive rates of AR protein expressions were75.0%、60.0%and10.0%respectively with statistical difference in general.5. In CRC group,the positive rates of ADAM17,TGF-α and AR protein expressions of metastastic group were higher than that of non-metastastic group with significant difference. The positive rates of ADAM17and AR protein expressions of T3+T4group were higher than that of T1+T2group with significant difference.6. The positive rates of ADAM17and AR protein expressions in adenomas with high grade glandular intraepithelial neoplasia were higher than that in adenomas with low grade glandular intraepithelial neoplasia with significant difference.7. The protein expressions of ADAM17were correlated with those of TGF-α and AR in CRC and adenoma groups.Conclusions:1. In the sequence of adjacent-to-tumor-non-neoplastic mucosa,adenoma and CRC,the protein staining of AD AM17, TGF-α and AR got stronger and the positive rates of ADAM17, TGF-α and AR protein expressions got higher progressively.2. The positive rates of ADAM17, TGF-α and AR protein expressions in CRC group were higher than that in adjacent-to-tumor-non-neoplastic mucosa groups.3. The expression levels of ADAM17, TGF-α and AR proteins were correlated with distant metastases of CRC.4. The expression levels of ADAM17and AR proteins were correlated with the grade of glandular intraepithelial neoplasia of adenoma.5. The protein expressions of ADAM17were correlated with those of TGF-α and AR in CRC and adenoma groups.6. ADAM17, TGF-α and AR proteins may play important roles in the adenoma-carcinoma sequence and act as diagnostic and prognostic biomarkers for CRC and colorectal adenoma.