Partial PTEN deletion is linked to poor prognosis in breast cancer
Standard
Partial PTEN deletion is linked to poor prognosis in breast cancer. / Lebok, P; Kopperschmidt, V; Kluth, M; Hube-Magg, C; Özden, C; Taskin, B; Hussein, K; Mittenzwei, A; Lebeau, A; Witzel, I; Wölber, L; Mahner, S; Jänicke, F; Geist, S; Paluchowski, P; Wilke, C; Heilenkötter, U; Simon, Ronald; Sauter, Guido; Terracciano, L; Krech, R; von der Assen, A; Müller, V; Burandt, E.
In: BMC CANCER, Vol. 15, No. 1, 2015, p. 963.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Partial PTEN deletion is linked to poor prognosis in breast cancer
AU - Lebok, P
AU - Kopperschmidt, V
AU - Kluth, M
AU - Hube-Magg, C
AU - Özden, C
AU - Taskin, B
AU - Hussein, K
AU - Mittenzwei, A
AU - Lebeau, A
AU - Witzel, I
AU - Wölber, L
AU - Mahner, S
AU - Jänicke, F
AU - Geist, S
AU - Paluchowski, P
AU - Wilke, C
AU - Heilenkötter, U
AU - Simon, Ronald
AU - Sauter, Guido
AU - Terracciano, L
AU - Krech, R
AU - von der Assen, A
AU - Müller, V
AU - Burandt, E
PY - 2015
Y1 - 2015
N2 - BACKGROUND: Deletions of chromosome 10q23, including the PTEN (phosphatase and tensin homolog) locus, are known to occur in breast cancer, but systematic analyses of its clinical relevance are lacking.METHODS: We thus analyzed a tissue microarray (TMA) with 2,197 breast cancers by fluorescence in-situ hybridization (FISH) using a PTEN-specific probe.RESULTS: PTEN deletions were detected in 19 % of no special type, 9 % of lobular, 4 % of tubular cancers and 46 % in carcinomas with medullary features. 98.7 % of deletions were heterozygous and only 1.3 % were homozygous. PTEN deletion was significantly linked to advanced tumor stage (p = 0.0054), high-grade (p < 0.0001), high tumor cell proliferation (Ki67 Labeling Index; p < 0.0001), and shortened overall survival (p = 0.0090). PTEN deletions were inversely associated with features of luminal type breast cancers (ER/PR positivity; p < 0.0001 each, and CCND1 amplification; p = 0.0020). PTEN deletions were also strongly linked to amplification of genes involved in the PTEN/AKT pathway such as MYC (p = 0.0430) and HER2 (p = 0.0065). Remarkably the combined analysis of MYC, HER2, CCND1 and PTEN aberrations suggested that aberrations of multiple PTEN/AKT pathway genes have a strong additive effect on breast cancer prognosis. While cancers with one of these aberrations behaved only marginally different from cancers with none, disease outcome was markedly worse in cancers with two or more aberrations as compared to those with only one aberration (p = 0.0002). In addition, the particularly poor prognosis of patients with HER2 amplification and PTEN deletions challenges the concept of PTEN deletions interfering with trastuzumab therapy.CONCLUSION: PTEN deletion occurs in a relevant fraction of breast cancers, and is linked to aggressive tumor behavior. Reduced PTEN function cooperates with MYC and HER2 activation in conferring aggressive phenotype to cancer cells.
AB - BACKGROUND: Deletions of chromosome 10q23, including the PTEN (phosphatase and tensin homolog) locus, are known to occur in breast cancer, but systematic analyses of its clinical relevance are lacking.METHODS: We thus analyzed a tissue microarray (TMA) with 2,197 breast cancers by fluorescence in-situ hybridization (FISH) using a PTEN-specific probe.RESULTS: PTEN deletions were detected in 19 % of no special type, 9 % of lobular, 4 % of tubular cancers and 46 % in carcinomas with medullary features. 98.7 % of deletions were heterozygous and only 1.3 % were homozygous. PTEN deletion was significantly linked to advanced tumor stage (p = 0.0054), high-grade (p < 0.0001), high tumor cell proliferation (Ki67 Labeling Index; p < 0.0001), and shortened overall survival (p = 0.0090). PTEN deletions were inversely associated with features of luminal type breast cancers (ER/PR positivity; p < 0.0001 each, and CCND1 amplification; p = 0.0020). PTEN deletions were also strongly linked to amplification of genes involved in the PTEN/AKT pathway such as MYC (p = 0.0430) and HER2 (p = 0.0065). Remarkably the combined analysis of MYC, HER2, CCND1 and PTEN aberrations suggested that aberrations of multiple PTEN/AKT pathway genes have a strong additive effect on breast cancer prognosis. While cancers with one of these aberrations behaved only marginally different from cancers with none, disease outcome was markedly worse in cancers with two or more aberrations as compared to those with only one aberration (p = 0.0002). In addition, the particularly poor prognosis of patients with HER2 amplification and PTEN deletions challenges the concept of PTEN deletions interfering with trastuzumab therapy.CONCLUSION: PTEN deletion occurs in a relevant fraction of breast cancers, and is linked to aggressive tumor behavior. Reduced PTEN function cooperates with MYC and HER2 activation in conferring aggressive phenotype to cancer cells.
U2 - 10.1186/s12885-015-1770-3
DO - 10.1186/s12885-015-1770-3
M3 - SCORING: Journal article
C2 - 26672755
VL - 15
SP - 963
JO - BMC CANCER
JF - BMC CANCER
SN - 1471-2407
IS - 1
ER -
