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Year : 2012  |  Volume : 1  |  Issue : 2  |  Page : 57-64

Cancerogenesis in colorectal neoplasms: Evidence from early onset colorectal cancer

Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Correspondence Address:
Mahsa Molaei
Gastroenterology and Liver Diseases Research Center, Taleghani Hospital Shahid Beheshti University of Medical Sciences, Tehran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-0513.99562

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Objective: Majority of colorectal cancers (CRC) happen via two distinct mechanisms of genomic instability: chromosomal and microsatellite instability. The proportion to which colorectal cancers belong to these pathways is well addressed in literature. However, there is much paucity and controversy regarding this proportion in early onset CRC; therefore, in the present study, major proteins involved in chromosomal and microsatellite instability pathways were determined in 104 early-onset CRC specimens. Materials and Methods: Outcome measures comprised expression of 4 mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, PMS2), and two representative proteins of chromosomal instability pathway (P53 and β-catenin), which were determined by immunohistochemistry. Results: Twenty-nine cases (27.9%) had loss of expression of MMR proteins, of which 17 belonged to MutSα pathway and 12 to MutLα. Four tumors had solitary loss of PMS2. Tumors with abnormal MMR status were more likely to be right sided, and occurred mainly in familial setting (P<0.05). Seventy-four specimens (71.2%) had abnormal expression of P53 or β-catenin, of which 58 had P53 over-expression and 32 had abnormal β-catenin expression. There was an inverse association between P53 over-expression and abnormal MMR status (P<0.05). Conclusions: Taken together, our study demonstrated that loss of expression of MMR proteins happens more frequently in early-onset CRC, and on the contrary, the role of CIN pathway is less highlighted at the same time. Moreover, because of its ability to track the losses of expression of PMS2, IHC is recommended for determining the eligibility of mutation analysis of MMR genes, especially in younger ages.

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