Correlation of gene methylation in surgical margin imprints with locoregional recurrence in head and neck squamous cell carcinoma

Masamichi Hayashi, Gaosong Wu, Jong Lyel Roh, Xiaofei Chang, Xiufeng Li, Julie Ahn, Marla Goldsmith, Zubair Khan, Justin Bishop, Zhe Zhang, Xian Chong Zhou, Jeremy Richmon, Nishant Agrawal, Wayne M. Koch

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22 Citations (Scopus)

Abstract

BACKGROUND Securing negative surgical margins is a critical goal for head and neck surgery. Local recurrence develops even in some patients who have histologically negative surgical margins. Minimal residual tumor cells may lead to locoregional recurrence despite clear histologic margins reported at the time of resection of head and neck squamous cell carcinoma (HNSCC). To identify subclinical residual disease, the authors analyzed deep margin imprint samples collected on 1-layer nitrocellulose sheets. METHODS Bisulfite-treated DNA samples from 73 eligible patients were amplified by quantitative methylation-specific polymerase chain reaction (QMSP) targeting 6 genes (deleted in colorectal cancer [DCC], endothelin receptor type B [EDNRB], homeobox protein A9 [HOXA9], kinesin family member 1A [KIF1A], nidogen-2 [NID2], and N-methyl D-aspartate receptor subtype 2B [NR2B]). QMSP values were dichotomized as positive or negative. Associations between the QMSP status of deep margin samples and clinical outcomes were evaluated. RESULTS Two-gene methylation combinations among the genes DCC, EDNRB, and HOXA9 were associated with decreased locoregional recurrence-free survival, recurrence-free survival, and overall survival. The methylated gene combination of EDNRB and HOXA9 in margin imprints was the most powerful predictor of poor locoregional recurrence-free survival (hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.30-8.46; P = .012) independent of standard histologic factors. In addition, methylation of both EDNRB and HOXA9 indicated a trend toward reduced recurrence-free survival (HR, 2.74; 95% CI, 0.90-8.33; P = .075) and reduced OS (HR, 5.78; 95% CI, 0.75-44.7; P = .093) in multivariable analysis. CONCLUSIONS A panel of gene methylation targets in deep surgical margin imprints provides a potential predictive marker of postoperative locoregional recurrence. Intraoperative use of molecular margin imprint analysis may assist surgeons in obtaining rigorously negative surgical margins and improve the outcome of head and neck surgery. Cancer 2015;121:1957-1965.

Original languageEnglish (US)
Pages (from-to)1957-1965
Number of pages9
JournalCancer
Volume121
Issue number12
DOIs
StatePublished - Jun 1 2015

Fingerprint

Methylation
Endothelin B Receptors
Recurrence
Genes
Survival
Confidence Intervals
Polymerase Chain Reaction
Colorectal Neoplasms
Neck
Head
Kinesin
Collodion
Gene Targeting
Residual Neoplasm
Carcinoma, squamous cell of head and neck
Margins of Excision
N-Methyl-D-Aspartate Receptors
homeobox protein HOXA9
DNA
Neoplasms

Keywords

  • head and neck cancer
  • locoregional recurrence
  • methylation
  • squamous cell carcinoma
  • surgical margin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Correlation of gene methylation in surgical margin imprints with locoregional recurrence in head and neck squamous cell carcinoma. / Hayashi, Masamichi; Wu, Gaosong; Roh, Jong Lyel; Chang, Xiaofei; Li, Xiufeng; Ahn, Julie; Goldsmith, Marla; Khan, Zubair; Bishop, Justin; Zhang, Zhe; Zhou, Xian Chong; Richmon, Jeremy; Agrawal, Nishant; Koch, Wayne M.

In: Cancer, Vol. 121, No. 12, 01.06.2015, p. 1957-1965.

Research output: Contribution to journalArticle

Hayashi, M, Wu, G, Roh, JL, Chang, X, Li, X, Ahn, J, Goldsmith, M, Khan, Z, Bishop, J, Zhang, Z, Zhou, XC, Richmon, J, Agrawal, N & Koch, WM 2015, 'Correlation of gene methylation in surgical margin imprints with locoregional recurrence in head and neck squamous cell carcinoma', Cancer, vol. 121, no. 12, pp. 1957-1965. https://doi.org/10.1002/cncr.29303
Hayashi, Masamichi ; Wu, Gaosong ; Roh, Jong Lyel ; Chang, Xiaofei ; Li, Xiufeng ; Ahn, Julie ; Goldsmith, Marla ; Khan, Zubair ; Bishop, Justin ; Zhang, Zhe ; Zhou, Xian Chong ; Richmon, Jeremy ; Agrawal, Nishant ; Koch, Wayne M. / Correlation of gene methylation in surgical margin imprints with locoregional recurrence in head and neck squamous cell carcinoma. In: Cancer. 2015 ; Vol. 121, No. 12. pp. 1957-1965.
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abstract = "BACKGROUND Securing negative surgical margins is a critical goal for head and neck surgery. Local recurrence develops even in some patients who have histologically negative surgical margins. Minimal residual tumor cells may lead to locoregional recurrence despite clear histologic margins reported at the time of resection of head and neck squamous cell carcinoma (HNSCC). To identify subclinical residual disease, the authors analyzed deep margin imprint samples collected on 1-layer nitrocellulose sheets. METHODS Bisulfite-treated DNA samples from 73 eligible patients were amplified by quantitative methylation-specific polymerase chain reaction (QMSP) targeting 6 genes (deleted in colorectal cancer [DCC], endothelin receptor type B [EDNRB], homeobox protein A9 [HOXA9], kinesin family member 1A [KIF1A], nidogen-2 [NID2], and N-methyl D-aspartate receptor subtype 2B [NR2B]). QMSP values were dichotomized as positive or negative. Associations between the QMSP status of deep margin samples and clinical outcomes were evaluated. RESULTS Two-gene methylation combinations among the genes DCC, EDNRB, and HOXA9 were associated with decreased locoregional recurrence-free survival, recurrence-free survival, and overall survival. The methylated gene combination of EDNRB and HOXA9 in margin imprints was the most powerful predictor of poor locoregional recurrence-free survival (hazard ratio [HR], 3.31; 95{\%} confidence interval [CI], 1.30-8.46; P = .012) independent of standard histologic factors. In addition, methylation of both EDNRB and HOXA9 indicated a trend toward reduced recurrence-free survival (HR, 2.74; 95{\%} CI, 0.90-8.33; P = .075) and reduced OS (HR, 5.78; 95{\%} CI, 0.75-44.7; P = .093) in multivariable analysis. CONCLUSIONS A panel of gene methylation targets in deep surgical margin imprints provides a potential predictive marker of postoperative locoregional recurrence. Intraoperative use of molecular margin imprint analysis may assist surgeons in obtaining rigorously negative surgical margins and improve the outcome of head and neck surgery. Cancer 2015;121:1957-1965.",
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T1 - Correlation of gene methylation in surgical margin imprints with locoregional recurrence in head and neck squamous cell carcinoma

AU - Hayashi, Masamichi

AU - Wu, Gaosong

AU - Roh, Jong Lyel

AU - Chang, Xiaofei

AU - Li, Xiufeng

AU - Ahn, Julie

AU - Goldsmith, Marla

AU - Khan, Zubair

AU - Bishop, Justin

AU - Zhang, Zhe

AU - Zhou, Xian Chong

AU - Richmon, Jeremy

AU - Agrawal, Nishant

AU - Koch, Wayne M.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - BACKGROUND Securing negative surgical margins is a critical goal for head and neck surgery. Local recurrence develops even in some patients who have histologically negative surgical margins. Minimal residual tumor cells may lead to locoregional recurrence despite clear histologic margins reported at the time of resection of head and neck squamous cell carcinoma (HNSCC). To identify subclinical residual disease, the authors analyzed deep margin imprint samples collected on 1-layer nitrocellulose sheets. METHODS Bisulfite-treated DNA samples from 73 eligible patients were amplified by quantitative methylation-specific polymerase chain reaction (QMSP) targeting 6 genes (deleted in colorectal cancer [DCC], endothelin receptor type B [EDNRB], homeobox protein A9 [HOXA9], kinesin family member 1A [KIF1A], nidogen-2 [NID2], and N-methyl D-aspartate receptor subtype 2B [NR2B]). QMSP values were dichotomized as positive or negative. Associations between the QMSP status of deep margin samples and clinical outcomes were evaluated. RESULTS Two-gene methylation combinations among the genes DCC, EDNRB, and HOXA9 were associated with decreased locoregional recurrence-free survival, recurrence-free survival, and overall survival. The methylated gene combination of EDNRB and HOXA9 in margin imprints was the most powerful predictor of poor locoregional recurrence-free survival (hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.30-8.46; P = .012) independent of standard histologic factors. In addition, methylation of both EDNRB and HOXA9 indicated a trend toward reduced recurrence-free survival (HR, 2.74; 95% CI, 0.90-8.33; P = .075) and reduced OS (HR, 5.78; 95% CI, 0.75-44.7; P = .093) in multivariable analysis. CONCLUSIONS A panel of gene methylation targets in deep surgical margin imprints provides a potential predictive marker of postoperative locoregional recurrence. Intraoperative use of molecular margin imprint analysis may assist surgeons in obtaining rigorously negative surgical margins and improve the outcome of head and neck surgery. Cancer 2015;121:1957-1965.

AB - BACKGROUND Securing negative surgical margins is a critical goal for head and neck surgery. Local recurrence develops even in some patients who have histologically negative surgical margins. Minimal residual tumor cells may lead to locoregional recurrence despite clear histologic margins reported at the time of resection of head and neck squamous cell carcinoma (HNSCC). To identify subclinical residual disease, the authors analyzed deep margin imprint samples collected on 1-layer nitrocellulose sheets. METHODS Bisulfite-treated DNA samples from 73 eligible patients were amplified by quantitative methylation-specific polymerase chain reaction (QMSP) targeting 6 genes (deleted in colorectal cancer [DCC], endothelin receptor type B [EDNRB], homeobox protein A9 [HOXA9], kinesin family member 1A [KIF1A], nidogen-2 [NID2], and N-methyl D-aspartate receptor subtype 2B [NR2B]). QMSP values were dichotomized as positive or negative. Associations between the QMSP status of deep margin samples and clinical outcomes were evaluated. RESULTS Two-gene methylation combinations among the genes DCC, EDNRB, and HOXA9 were associated with decreased locoregional recurrence-free survival, recurrence-free survival, and overall survival. The methylated gene combination of EDNRB and HOXA9 in margin imprints was the most powerful predictor of poor locoregional recurrence-free survival (hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.30-8.46; P = .012) independent of standard histologic factors. In addition, methylation of both EDNRB and HOXA9 indicated a trend toward reduced recurrence-free survival (HR, 2.74; 95% CI, 0.90-8.33; P = .075) and reduced OS (HR, 5.78; 95% CI, 0.75-44.7; P = .093) in multivariable analysis. CONCLUSIONS A panel of gene methylation targets in deep surgical margin imprints provides a potential predictive marker of postoperative locoregional recurrence. Intraoperative use of molecular margin imprint analysis may assist surgeons in obtaining rigorously negative surgical margins and improve the outcome of head and neck surgery. Cancer 2015;121:1957-1965.

KW - head and neck cancer

KW - locoregional recurrence

KW - methylation

KW - squamous cell carcinoma

KW - surgical margin

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