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Can a Biomarker-Based Scoring System Predict Pathologic Complete Response After Preoperative Chemoradiotherapy for Rectal Cancer?

 Hyuk Hur  ;  Nam Kyu Kim  ;  Byung Soh Min  ;  Seung Hyuk Baik  ;  Kang Young Lee  ;  Woong Sub Koom  ;  Joong Bae Ahn  ;  Hoguen Kim 
 DISEASES OF THE COLON & RECTUM, Vol.57(5) : 592-601, 2014 
Journal Title
Issue Date
Adenocarcinoma/pathology* ; Adenocarcinoma/surgery ; Adenocarcinoma/therapy* ; Adult ; Aged ; Biomarkers, Tumor/analysis* ; Biopsy ; Chemoradiotherapy* ; Combined Modality Therapy ; Fluorouracil/therapeutic use ; Humans ; Leucovorin/therapeutic use ; Lymphatic Metastasis/pathology ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Polymerase Chain Reaction ; Predictive Value of Tests ; Radiotherapy Dosage ; Rectal Neoplasms/pathology* ; Rectal Neoplasms/surgery ; Rectal Neoplasms/therapy* ; Retrospective Studies ; Sigmoidoscopy ; Treatment Outcome
Rectal cancer ; Chemoradiotherapy ; Pathologic complete response ; Biomarkers ; Predictive system
BACKGROUND: Numerous molecular markers have been investigated as potential predictors of tumor responses to preoperative chemoradiotherapy (preCRT) for rectal cancer. OBJECTIVE: To develop a system in which biomarkers are used to predict the likelihood of a pathologic complete response (pCR) to preCRT. DESIGN & SETTING: This is a retrospective analysis of tumor specimens collected prior to preCRT from 81 patients who underwent curative resection for primary rectal adenocarcinoma between June 2008 and February 2012. MAIN OUTCOME MEASURES: Using tissue microarrays and immunohistochemistry, expression levels of twelve candidate biomarkers (p53, p21, Bcl2, Bax, EGFR, Cox-2, MLH-1, MSH-2, Ku70, VEGF, TS, Ki-67) were evaluated in paraffin-embedded tumor samples collected before preCRT. The correlation between biomarker expression levels and the pathologic response to preCRT was assessed based on histopathological staging (pTNM) and tumor regression grade (TRG). RESULTS: Expression levels of 4 biomarkers (p53, VEGF, p21, Ki67) correlated with pCR. Patients showing low expression of p53 and/or high expression of VEGF, p21, and Ki67 exhibited a significantly greater pCR rate. A scoring system devised so that one point was given for each biomarker whose expression level correlated with pCR (score range: 0-4) showed that 1 of 26 patients with scores of 0 to 1 achieved pCR, whereas 26 of 55 patients with scores of 2 to 4 achieved pCR (3.8% vs. 47.3%, p < 0.001). For prediction of pCR, the scoring system showed 96.3% sensitivity, 46.3% specificity, a 47.3% positive predictive value, and a 96.2% negative predictive value. LIMITATIONS: Immunohistochemistry has limitations related to reproducibility and the ability to provide quantitative information. In addition, this study lacks test and validation sets. CONCLUSIONS: Expression levels of 4 biomarkers correlated with pCR after preCRT for rectal cancer. A scoring system based on levels of biomarker expression showed good sensitivity and negative predictive value for pCR.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Koom, Woong Sub(금웅섭) ORCID logo https://orcid.org/0000-0002-9435-7750
Kim, Nam Kyu(김남규) ORCID logo https://orcid.org/0000-0003-0639-5632
Kim, Hogeun(김호근)
Min, Byung Soh(민병소) ORCID logo https://orcid.org/0000-0003-0180-8565
Baik, Seung Hyuk(백승혁) ORCID logo https://orcid.org/0000-0003-4183-2332
Ahn, Joong Bae(안중배) ORCID logo https://orcid.org/0000-0001-6787-1503
Lee, Kang Young(이강영)
Hur, Hyuk(허혁) ORCID logo https://orcid.org/0000-0002-9864-7229
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