title: ARID1A expression in early stage colorectal adenocarcinoma: an exploration of its prognostic significance.
abstract: ARID1A is a chromatin remodeling gene that is mutated in a number of cancers including colorectal carcinoma (CRC). Loss of ARID1A has been associated with an adverse outcome in some types of cancer. However, literature data have not been consistent. Major limitations of some outcome studies include small sample size and heterogeneous patient population. In this study, we evaluated the prognostic value of ARID1A in a homogeneous group of early stage CRC patients, a population where prognostic markers are particularly relevant. We collected a retrospective series of 578 stage I or II CRCs. All patients underwent surgery with curative intent and without neoadjuvant or adjuvant therapy. ARID1A expression was analyzed by immunohistochemistry using tissue microarray. We found ARID1A loss in 49 of 552 analyzable tumors (8.9%). Compared with the ARID1A-retained group, cases with ARID1A loss were associated with female sex (P<.001), mismatch-repair protein deficiency (P<.001), poor differentiation (P<.001), lymphovascular invasion (P=.001), and higher pT stage (P=.047). However, at a median follow-up of 49months, ARID1A loss did not correlate with overall, disease-specific, or recurrence-free survival. This is the first systematic analysis to evaluate the prognostic significance of ARID1A in stage I/II CRCs, and our data indicate that ARID1A loss lacks prognostic significance in this population despite its association with other adverse features. Such data are clinically relevant, as efforts are ongoing in identifying markers that can detect the small but significant subset of early stage CRCs that will have a poor outcome.
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065. Electronic address: leel1@mskcc.org.
authors.forename: Lik Hang
authors.initials: LH
authors.lastname: Lee
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065. Electronic address: sadote@mskcc.org.
authors.forename: Eran
authors.initials: E
authors.lastname: Sadot
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065. Electronic address: sinisa.ivelja@gmail.com.
authors.forename: Sinisa
authors.initials: S
authors.lastname: Ivelja
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065. Electronic address: vakianie@mskcc.org.
authors.forename: Efsevia
authors.initials: E
authors.lastname: Vakiani
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065. Electronic address: hechtmaj@mskcc.org.
authors.forename: Jaclyn F
authors.initials: JF
authors.lastname: Hechtman
authors.affiliation: Life Sciences & Molecular Diagnostics, GE Global Research, General Electric Company, 1 Research Circle, Niskayuna, NY, 12309. Electronic address: sevinsky@ge.com.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sevinsky
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065. Electronic address: klimstrd@mskcc.org.
authors.forename: David S
authors.initials: DS
authors.lastname: Klimstra
authors.affiliation: Life Sciences & Molecular Diagnostics, GE Global Research, General Electric Company, 1 Research Circle, Niskayuna, NY, 12309. Electronic address: ginty@research.ge.com.
authors.forename: Fiona
authors.initials: F
authors.lastname: Ginty
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065. Electronic address: shiaj@mskcc.org.
authors.forename: Jinru
authors.initials: J
authors.lastname: Shia
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000628:therapy; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000172:deficiency; D004268:DNA-Binding Proteins; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013997:Time Factors; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000032:analysis*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C112476:ARID1A protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D045643:DNA Repair Enzymes
keywords: ARID1A; Biomarker; Colorectal adenocarcinoma; Immunohistochemistry; Microsatellite instability