Molecular characterization of late stomal recurrence following total laryngectomy

  • Authors:
    • Josena K. Stephen
    • Mausumi Symal
    • Kang Mei Chen
    • Tamer Ghanem
    • Robert Deeb
    • Veena Shah
    • Shaleta Havard
    • Maria J. Worsham
  • View Affiliations

  • Published online on: January 10, 2011     https://doi.org/10.3892/or.2011.1136
  • Pages: 669-676
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Abstract

The goal was to determine recurrent or second primary status for late stomal malignancies, 16 and 17 years post-total laryngectomy in two laryngeal squamous cell carcinoma (LSCC) patients, based on DNA methylation signatures and HPV typing. Adopting a literature review based definition of late stomal recurrences as new primaries at the site of the stoma or neopharynx occurring >5 years after total laryngectomy, we employed a multi-gene candidate approach to examine promoter methylation in 24 tumor suppressor genes and PCR-based assays for HPV status offered additional insights into whether the late stomal tumors post-total laryngectomy were related or not. The primary tumor for Patient 1 was negative for HPV but had aberrant hypermethylation of APC, MLH1 and BRCA1. The stomal biopsy 17-years later showed presence of HPV-16 without any methylated genes. In Patient 2, HPV-11 and promoter methylation of APC identified in the primary tumor was also observed in the stomal malignancy 16 years post-total laryngectomy. Additional information provided by molecular typing for HPV and methylation markers underscored Patient 1's and 2's late stomal presentation as most likely a second primary and recurrence, respectively. DNA methylation markers are particularly advantageous because DNA methylation is an early event in tumorigenesis, and the epigenetic modification, 5-methylcytosine, is a stable marker. Molecular marks to discern genetic heterogeneity or relatedness of stomal malignancies several years post-total laryngectomy can provide clues to their status as either second primaries or likely recurrences. Our results support the hypothesis that a subset of stomal recurrences after total laryngectomy represents second primary tumors.

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March 2011
Volume 25 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Stephen JK, Symal M, Chen KM, Ghanem T, Deeb R, Shah V, Havard S and Worsham MJ: Molecular characterization of late stomal recurrence following total laryngectomy. Oncol Rep 25: 669-676, 2011.
APA
Stephen, J.K., Symal, M., Chen, K.M., Ghanem, T., Deeb, R., Shah, V. ... Worsham, M.J. (2011). Molecular characterization of late stomal recurrence following total laryngectomy. Oncology Reports, 25, 669-676. https://doi.org/10.3892/or.2011.1136
MLA
Stephen, J. K., Symal, M., Chen, K. M., Ghanem, T., Deeb, R., Shah, V., Havard, S., Worsham, M. J."Molecular characterization of late stomal recurrence following total laryngectomy". Oncology Reports 25.3 (2011): 669-676.
Chicago
Stephen, J. K., Symal, M., Chen, K. M., Ghanem, T., Deeb, R., Shah, V., Havard, S., Worsham, M. J."Molecular characterization of late stomal recurrence following total laryngectomy". Oncology Reports 25, no. 3 (2011): 669-676. https://doi.org/10.3892/or.2011.1136