title: Altered PTEN function caused by deletion or gene disruption is associated with poor prognosis in rectal but not in colon cancer.
abstract: Colorectal cancer is the third most common malignancy worldwide. Anti-epidermal growth factor receptor (EGFR)-targeted therapy shows clinical evidence in this malignancy and improves outcome. The tumor suppressor gene phosphatase and tensin homologue (PTEN) is considered a potential predictor of nonresponse to anti-EGFR agents. The purpose of this study was to assess whether associations between PTEN alterations (PTEN gene deletion or PTEN gene disruption) and clinical outcome could be caused by a prognostic (and not predictive) effect of PTEN inactivation. Therefore, we analyzed 404 colorectal cancers not previously treated with anti-EGFR drugs in a tissue microarray format. PTEN deletion and PTEN gene rearrangements were analyzed by fluorescence in situ hybridization. Heterogeneity analysis of all available large tissue sections was performed in 6 cases with genomic PTEN alteration. Twenty-seven (8.8%) of 307 analyzable colorectal cancer spots showed genomic PTEN alterations including 24 hemizygous and 1 homozygous deletion as well as 2 PTEN gene disruptions. Genomic PTEN alterations were associated with reduced patient survival in rectal cancer in univariate and multivariate analyses (P = .012; hazard ratio, 2.675; 95% confidence interval, 1.242-5.759) but not in colon cancer. Large-section evaluation revealed a homogeneous distribution pattern in all 4 analyzed cases with PTEN deletion and in both cases with a PTEN gene disruption. In conclusion, genomic PTEN gene alterations caused by deletion or gene disruption characterize a fraction of rectal cancers with particularly poor outcome.
authors: General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors: B A
authors: BA
authors: Bohn
authors: S
authors: S
authors: Mina
authors: A
authors: A
authors: Krohn
authors: R
authors: R
authors: Simon
authors: M
authors: M
authors: Kluth
authors: S
authors: S
authors: Harasimowicz
authors: A
authors: A
authors: Quaas
authors: M
authors: M
authors: Bockhorn
authors: J R
authors: JR
authors: Izbicki
authors: G
authors: G
authors: Sauter
authors: A
authors: A
authors: Marx
authors: P R
authors: PR
authors: Stahl
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Colorectal neoplasms; Fluorescence in situ hybridization; Gene deletion; PTEN phosphohydrolase