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Epigenetic down‐regulation of SOX 2 is an independent poor prognostic factor for hypopharyngeal cancers
Author(s) -
Avincsal Mehmet Ozgur,
Jimbo Naoe,
Fujikura Kohei,
Shinomiya Hirotaka,
Otsuki Naoki,
Morimoto Koichi,
Furukawa Tatsuya,
Morita Naruhiko,
Maehara Ritsuko,
Itoh Tomoo,
Nibu Kenichi,
Zen Yoh
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13436
Subject(s) - medicine , immunostaining , cell , immunohistochemistry , pathology , biology , genetics
Aims We recently reported that a small subset (7%) of oesophageal squamous cell carcinomas completely lacking SOX 2 expression had unique clinicopathological features and a dismal prognosis. The aim of the present study was to elucidate whether the findings obtained in oesophageal cancers are applicable to hypopharyngeal squamous cell carcinomas ( HPSCC s) or oropharyngeal squamous cell carcinomas ( OPSCC s). Methods and results The study cohort consisted of consecutive patients with HPSCC ( n = 130) and OPSCC ( n = 65) who underwent surgery without preoperative therapy. On immunostaining, SOX 2 was almost entirely negative in 10 of 130 HPSCC s (8%) and seven of 65 OPSCC s (11%). No significant differences were observed in clinicopathological features, including p16 status, between SOX 2‐positive and SOX 2‐negative cancers. However, patients with SOX 2‐negative HPSCC had significantly worse overall and recurrence‐free survival than those with SOX 2‐positive HPSCC , whereas such a prognostic relationship was not confirmed in patients with OPSCC . In a multivariate analysis, the loss of SOX 2 expression appeared to be an independent poor prognostic factor for patients with HPSCC . In a sequencing analysis, no mutation was found in SOX 2 . As SOX 2 is known to contain an extensive CpG island before the transcription start site, methylation‐specific polymerase chain reaction for the SOX 2 promoter was performed. Methylated alleles were found in nine of 10 SOX 2‐negative HPSCC s but in none of SOX 2‐positive HPSCC s. Conclusions Similarly to oesophageal cancers, a small subset (8%) of HPSCC s characteristically almost completely lacking SOX 2 expression appeared to be aggressive neoplasms with high recurrence rates. Promoter hypermethylation was determined to be a major mechanism underlying epigenetic SOX 2 silencing.