title: Loss of PTEN is associated with elevated EGFR and HER2 expression and worse prognosis in salivary gland cancer.
abstract: BACKGROUND
  Activity of the tumour-suppressor gene PTEN is reduced in different types of cancer and implicates non-responsiveness to targeted therapy. This study evaluates the gene and protein status of PTEN in salivary gland carcinomas.
  
  
  METHODS
  A total of 287 carcinomas of the major and minor salivary glands were investigated for phosphatase and tensin homologue located on chromosome 10 (PTEN) deletion and loss of PTEN expression using fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC), respectively. Results were correlated to clinicopathological parameters, long-term survival, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) (IHC and FISH) status of the tumours.
  
  
  RESULTS
  Hemizygous deletions of PTEN were found in 35 out of 232 (15.1%) carcinomas, while homozygous deletions were observed in 17 out of 232 (7.3%) tumours. Phosphatase and tensin homologue located on chromosome 10 deletion was common in certain histological subtypes and especially homozygous deletion was associated with high-grade malignancy, lymph node metastases and unfavourable long-term prognosis (P<0.001). Loss of PTEN expression was present in 59 out of 273 (21.6%) carcinomas and was significantly correlated to genomic PTEN deletion, high-grade malignancy (P<0.001), increased tumour size (P=0.036), lymph node metastases (P=0.007) and worse disease-specific survival (P=0.002). Genomic PTEN deletion, in particular homogenous deletion (P<0.001) predominantly occurred in tumours with increased gene copy number of EGFR (60.0%) and/or amplification of HER2 (63.6%). Loss of PTEN expression was frequently found in tumours overexpressing EGFR (28.6%) and/or HER2 (52.6%).
  
  
  CONCLUSIONS
  PTEN function is reduced in different types of salivary gland cancer indicating unfavourable prognosis. Its association with EGFR and HER2 signalling might affect targeted therapy.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. tobias.ettl@klinik.uni-regensburg.de
authors.forename: T
authors.initials: T
authors.lastname: Ettl
authors.forename: K
authors.initials: K
authors.lastname: Baader
authors.forename: C
authors.initials: C
authors.lastname: Stiegler
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: A
authors.initials: A
authors.lastname: Agaimy
authors.forename: J
authors.initials: J
authors.lastname: Zenk
authors.forename: T
authors.initials: T
authors.lastname: Kühnel
authors.forename: M
authors.initials: M
authors.lastname: Gosau
authors.forename: K
authors.initials: K
authors.lastname: Zeitler
authors.forename: S
authors.initials: S
authors.lastname: Schwarz
authors.forename: G
authors.initials: G
authors.lastname: Brockhoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology
chemical_list: D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases; C494929:PTEN protein, human