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Downregulation of human leukocyte antigen Class I expression: An independent prognostic factor in colorectal cancer


1 Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Department of Immunology, Medical School, Shahid Beheshti University of Medical Sciences, Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
5 Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Tehran, Iran

Correspondence Address:
Mohammad Reza Zali,
Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, P.O. Box: 19857-17411, Yeman Street, Chamran Expressway, Tehran
Iran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_429_18

Aim: In the present study, we evaluated the clinical prognostic value of human leukocyte antigen (HLA (Class I tumor cell expression in a series of colorectal cancer (CRC) patients and also explored the association of this expression profile with molecular features such as mutation status of KRAS and BRAF, microsatellite stability status, and clinicopathological characteristics of the patients. Patients and Methods: Formalin-fixed paraffin-embedded tumor tissue of 258 CRC patient's sections were immunohistochemically stained and subsequently quantified for HLA Class I expression by the tumor cells. Determination of microsatellite instability (MSI) tumor status was ascertained using mononucleotide repeat microsatellite targets. KRAS and BRAF mutations were screened by polymerase chain reaction (PCR)-sequencing and cast-PCR, respectively. Results: HLA Class I expression was normal in 91 cases (35.3%), downregulated in 119 (46.1%), and loss of expression in 48 (18.6%) cases. Forty (15.5%) tumors were MSI-H (MSH), 49 were MSI-L (19%), and 169 were microsatellite stable (MSS) (65.5%). Thirty-six (14%) and 15 (5.8%) of the patients exhibited mutation in the KRAS and BRAF, respectively. It was found that patients with downregulated expression of HLA Class I were associated with Stage II tumors (P < 0.001) and a MSS tumor status (P < 0.001), while patients with loss of expression were associated with MSH status (P < 0.001). Univariate and multivariate analyses revealed that HLA Class I downregulated expression was an independent prognostic parameter for shorter overall patient survival time (hazard ratio: 1.8, P = 0.003). Conclusions:HLA Class I expression is an independent and sensitive clinical prognostic marker that might be used in CRC patients.


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    -  Nazemalhosseini-Mojarad E
    -  Asadzadeh-Aghdaei H
    -  Mohammadpour S
    -  Esfahani AT
    -  Porhoseingholi MA
    -  Molaei M
    -  Jalali A
    -  K. Kuppen PJ
    -  Zali MR
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