Altered PTEN function caused by deletion or gene disruption is associated with poor prognosis in rectal but not in colon cancer
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Altered PTEN function caused by deletion or gene disruption is associated with poor prognosis in rectal but not in colon cancer. / Bohn, B A; Mina, S; Krohn, A; Simon, R; Kluth, M; Harasimowicz, Silvia; Quaas, A; Bockhorn, M; Izbicki, J R; Sauter, G; Marx, A; Stahl, P R.
in: HUM PATHOL, Jahrgang 44, Nr. 8, 01.08.2013, S. 1524-33.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Altered PTEN function caused by deletion or gene disruption is associated with poor prognosis in rectal but not in colon cancer
AU - Bohn, B A
AU - Mina, S
AU - Krohn, A
AU - Simon, R
AU - Kluth, M
AU - Harasimowicz, Silvia
AU - Quaas, A
AU - Bockhorn, M
AU - Izbicki, J R
AU - Sauter, G
AU - Marx, A
AU - Stahl, P R
N1 - Copyright © 2013 Elsevier Inc. All rights reserved.
PY - 2013/8/1
Y1 - 2013/8/1
N2 - 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.
AB - 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.
KW - Aged
KW - Colonic Neoplasms
KW - Female
KW - Gene Deletion
KW - Humans
KW - In Situ Hybridization, Fluorescence
KW - Kaplan-Meier Estimate
KW - Male
KW - Middle Aged
KW - PTEN Phosphohydrolase
KW - Prognosis
KW - Proportional Hazards Models
KW - Rectal Neoplasms
KW - Tissue Array Analysis
KW - Tumor Markers, Biological
U2 - 10.1016/j.humpath.2012.12.006
DO - 10.1016/j.humpath.2012.12.006
M3 - SCORING: Journal article
C2 - 23465274
VL - 44
SP - 1524
EP - 1533
JO - HUM PATHOL
JF - HUM PATHOL
SN - 0046-8177
IS - 8
ER -