Can a biomarker-based scoring system predict pathologic complete response after preoperative chemoradiotherapy for rectal cancer?

Hyuk Hur, Namkyu Kim, Byung Soh Min, Seung Hyuk Baik, Kang Young Lee, Woong Sub Koom, Joong Bae Ahn, Hoguen Kim

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)592-601
Number of pages10
JournalDiseases of the Colon and Rectum
Volume57
Issue number5
DOIs
Publication statusPublished - 2014 Jan 1

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Chemoradiotherapy
Rectal Neoplasms
Biomarkers
Vascular Endothelial Growth Factor A
Immunohistochemistry
Melanocyte-Stimulating Hormones
Neoplasms
Neoplasm Staging
Paraffin
Adenocarcinoma
Sensitivity and Specificity

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Hur, Hyuk ; Kim, Namkyu ; Min, Byung Soh ; Baik, Seung Hyuk ; Lee, Kang Young ; Koom, Woong Sub ; Ahn, Joong Bae ; Kim, Hoguen. / Can a biomarker-based scoring system predict pathologic complete response after preoperative chemoradiotherapy for rectal cancer?. In: Diseases of the Colon and Rectum. 2014 ; Vol. 57, No. 5. pp. 592-601.
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title = "Can a biomarker-based scoring system predict pathologic complete response after preoperative chemoradiotherapy for rectal cancer?",
abstract = "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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Can a biomarker-based scoring system predict pathologic complete response after preoperative chemoradiotherapy for rectal cancer? / Hur, Hyuk; Kim, Namkyu; Min, Byung Soh; Baik, Seung Hyuk; Lee, Kang Young; Koom, Woong Sub; Ahn, Joong Bae; Kim, Hoguen.

In: Diseases of the Colon and Rectum, Vol. 57, No. 5, 01.01.2014, p. 592-601.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Can a biomarker-based scoring system predict pathologic complete response after preoperative chemoradiotherapy for rectal cancer?

AU - Hur, Hyuk

AU - Kim, Namkyu

AU - Min, Byung Soh

AU - Baik, Seung Hyuk

AU - Lee, Kang Young

AU - Koom, Woong Sub

AU - Ahn, Joong Bae

AU - Kim, Hoguen

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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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