PMID- 21225233
OWN - NLM
STAT- MEDLINE
DCOM- 20110509
LR  - 20211020
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 25
IP  - 3
DP  - 2011 Mar
TI  - Molecular characterization of late stomal recurrence following total 
      laryngectomy.
PG  - 669-76
LID - 10.3892/or.2011.1136 [doi]
AB  - 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.
FAU - Stephen, Josena K
AU  - Stephen JK
AD  - Department of Otolaryngology/Head and Neck Surgery, Henry Ford Hospital, Detroit, 
      MI 48202, USA.
FAU - Symal, Mausumi
AU  - Symal M
FAU - Chen, Kang Mei
AU  - Chen KM
FAU - Ghanem, Tamer
AU  - Ghanem T
FAU - Deeb, Robert
AU  - Deeb R
FAU - Shah, Veena
AU  - Shah V
FAU - Havard, Shaleta
AU  - Havard S
FAU - Worsham, Maria J
AU  - Worsham MJ
LA  - eng
GR  - R01 DE015990/DE/NIDCR NIH HHS/United States
GR  - R01 DE 15990/DE/NIDCR NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110110
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
SB  - IM
MH  - Aged
MH  - Carcinoma, Squamous Cell/complications/*genetics/pathology/*surgery
MH  - DNA Methylation
MH  - Epigenomics
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Human papillomavirus 11/genetics/physiology
MH  - Human papillomavirus 16/genetics/physiology
MH  - Humans
MH  - Laryngeal Neoplasms/complications/*genetics/pathology/*surgery
MH  - Laryngectomy/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/complications/*genetics/pathology
MH  - Neoplasms, Second Primary/complications/genetics/pathology
MH  - Papillomavirus Infections/complications/genetics/pathology
MH  - Surgical Stomas/*pathology
PMC - PMC3718469
MID - NIHMS486601
EDAT- 2011/01/13 06:00
MHDA- 2011/05/10 06:00
PMCR- 2013/07/22
CRDT- 2011/01/13 06:00
PHST- 2010/09/24 00:00 [received]
PHST- 2010/10/27 00:00 [accepted]
PHST- 2011/01/13 06:00 [entrez]
PHST- 2011/01/13 06:00 [pubmed]
PHST- 2011/05/10 06:00 [medline]
PHST- 2013/07/22 00:00 [pmc-release]
AID - 10.3892/or.2011.1136 [doi]
PST - ppublish
SO  - Oncol Rep. 2011 Mar;25(3):669-76. doi: 10.3892/or.2011.1136. Epub 2011 Jan 10.