Loss of PTEN is associated with elevated EGFR and HER2 expression and worse prognosis in salivary gland cancer

Department of Oral and Maxillofacial Surgery, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
British Journal of Cancer (Impact Factor: 4.84). 02/2012; 106(4):719-26. DOI: 10.1038/bjc.2011.605
Source: PubMed

ABSTRACT 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.
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.
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%).
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.

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Available from: Gero Brockhoff, Sep 26, 2015
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    • "PTEN (SpectrumOrange) and chromosomal enumeration probe 10 (CEP10, Spectrum Green) FISH was performed as per manufacturer’s recommendations (Abbot Molecular, Des Plaines, IL, USA) and as previously described [22]. Results were interpreted using previously established thresholds [23,24]: PTEN homozygous deletion was defined as >20% of cells without PTEN locus signal and the presence of ≥2 CEP10 signals. Hemizygous PTEN deletion was defined as >30% of cells with only one PTEN signal and the presence of ≥2 CEP10 signals. "
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    • "Analysis of microarray data from cell lines and bulk tumors isolated from human neurofibromas and MPNSTs indicate that there is a selective pressure to lose PTEN expression, while EGFR expression is induced during disease progression (Figures 4(a) and 4(b)). It has recently been shown that loss of PTEN is associated with elevated EGFR and HER2 expression and worse prognosis in salivary gland cancer, further demonstrating the importance of these two genes in other cancer types [32]. In the current study, we have provided genetic evidence that loss of Pten cooperates with EGFR overexpression in Schwann cells, in the evolution from a low-grade to high-grade PNST using our GEMM. "
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