title: SOX2 amplification is a common event in squamous cell carcinomas of different organ sites.
abstract: Acquired chromosomal aberrations, including gene copy number alterations, are involved in the development and progression of human malignancies. SOX2, a transcription factor-coding gene located at 3q26.33, is known to be recurrently and specifically amplified in squamous cell carcinomas of the lung, the esophagus, and the oral cavity. In these organs, the SOX2 protein plays an important role in tumorigenesis and tumor survival. The aim of this study was to determine whether SOX2 amplification is also found in squamous cell carcinomas in other organs commonly affected by this tumor entity. In addition, we examined a large spectrum of lung cancer entities with neuroendocrine differentiation (ie, small cell cancers, large cell cancers, typical and atypical carcinoids) for SOX2 and TTF1 copy number gains to reveal potential molecular ties to squamous cell carcinomas or adenocarcinomas of the lung. Applying fluorescence in situ hybridization, we assessed squamous cell carcinomas of the cervix uteri (n = 47), the skin (n = 57), and the penis (n = 53) for SOX2 copy number alterations and detected amplifications in 28%, 28%, and 32% of tumors, respectively. Furthermore, we performed immunohistochemical SOX2 staining and found that SOX2 amplification is significantly associated with overexpression of the corresponding protein in squamous cell carcinomas (P < .001). Of the lung cancer entities with neuroendocrine differentiation, only small cell cancers and large cell cancers exhibited SOX2 or TTF1 amplifications at significant frequencies, indicating that at least a subset of these might be dedifferentiated forms of squamous cell carcinomas or adenocarcinomas of the lung. We conclude that SOX2 amplification and consequent SOX2 protein overexpression may represent important mechanisms of tumor initiation and progression in a considerable subset of squamous cell carcinomas.
authors.affiliation: Institute of Pathology, Comprehensive Cancer Center, University Hospital of Tuebingen, 72076 Tuebingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Maier
authors.forename: Theresia
authors.initials: T
authors.lastname: Wilbertz
authors.forename: Martin
authors.initials: M
authors.lastname: Braun
authors.forename: Veit
authors.initials: V
authors.lastname: Scheble
authors.forename: Markus
authors.initials: M
authors.lastname: Reischl
authors.forename: Ralf
authors.initials: R
authors.lastname: Mikut
authors.forename: Roopika
authors.initials: R
authors.lastname: Menon
authors.forename: Pavel
authors.initials: P
authors.lastname: Nikolov
authors.forename: Karen
authors.initials: K
authors.lastname: Petersen
authors.forename: Christine
authors.initials: C
authors.lastname: Beschorner
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Christoph
authors.initials: C
authors.lastname: Kakies
authors.forename: Chris
authors.initials: C
authors.lastname: Protzel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bauer
authors.forename: Alex
authors.initials: A
authors.lastname: Soltermann
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Annette
authors.initials: A
authors.lastname: Staebler
authors.forename: Claudia
authors.initials: C
authors.lastname: Lengerke
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018196:Carcinoma, Adenosquamous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D004273:DNA, Neoplasm; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors