8p deletion is strongly linked to poor prognosis in breast cancer
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8p deletion is strongly linked to poor prognosis in breast cancer. / Lebok, P; Mittenzwei, A; Kluth, M; Özden, C; Taskin, B; Hussein, Kais; Möller, K; Hartmann, A; Lebeau, A; Witzel, I; Mahner, S; Wölber, L; Jänicke, F; Geist, S; Paluchowski, P; Wilke, C; Heilenkötter, U; Simon, R; Sauter, G; Terracciano, L; Krech, R; von der Assen, A; Müller, V; Burandt, E.
In: CANCER BIOL THER, Vol. 16, No. 7, 2015, p. 1080-7.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - 8p deletion is strongly linked to poor prognosis in breast cancer
AU - Lebok, P
AU - Mittenzwei, A
AU - Kluth, M
AU - Özden, C
AU - Taskin, B
AU - Hussein, Kais
AU - Möller, K
AU - Hartmann, A
AU - Lebeau, A
AU - Witzel, I
AU - Mahner, S
AU - Wölber, L
AU - Jänicke, F
AU - Geist, S
AU - Paluchowski, P
AU - Wilke, C
AU - Heilenkötter, U
AU - Simon, R
AU - Sauter, G
AU - Terracciano, L
AU - Krech, R
AU - von der Assen, A
AU - Müller, V
AU - Burandt, E
PY - 2015
Y1 - 2015
N2 - Deletions of chromosome 8p occur frequently in breast cancers, but analyses of its clinical relevance have been limited to small patient cohorts and provided controversial results. A tissue microarray with 2,197 breast cancers was thus analyzed by fluorescence in-situ hybridization using an 8p21 probe in combination with a centromere 8 reference probe. 8p deletions were found in 50% of carcinomas with no special type, 67% of papillary, 28% of tubular, 37% of lobular cancers and 56% of cancers with medullary features. Deletions were always heterozygous. 8p deletion was significantly linked to advanced tumor stage (P < 0.0001), high-grade (P < 0.0001), high tumor cell proliferation (Ki67 Labeling Index; P < 0.0001), and shortened overall survival (P < 0.0001). For example, 8p deletion was seen in 32% of 290 grade 1, 43% of 438 grade 2, and 65% of 427 grade 3 cancers. In addition, 8p deletions were strongly linked to amplification of MYC (P < 0.0001), HER2 (P < 0.0001), and CCND1 (p = 0.001), but inversely associated with ER receptor expression (p = 0.0001). Remarkably, 46.5% of 8p-deleted cancers harbored amplification of at least one of the analyzed genes as compared to 27.5% amplifications in 8p-non-deleted cancers (P < 0.0001). In conclusion, 8p deletion characterizes a subset of particularly aggressive breast cancers. As 8p deletions are easy to analyze, this feature appears to be highly suited for future DNA based prognostic breast cancer panels. The strong link of 8p deletion with various gene amplifications raises the possibility of a role for regulating genomic stability.
AB - Deletions of chromosome 8p occur frequently in breast cancers, but analyses of its clinical relevance have been limited to small patient cohorts and provided controversial results. A tissue microarray with 2,197 breast cancers was thus analyzed by fluorescence in-situ hybridization using an 8p21 probe in combination with a centromere 8 reference probe. 8p deletions were found in 50% of carcinomas with no special type, 67% of papillary, 28% of tubular, 37% of lobular cancers and 56% of cancers with medullary features. Deletions were always heterozygous. 8p deletion was significantly linked to advanced tumor stage (P < 0.0001), high-grade (P < 0.0001), high tumor cell proliferation (Ki67 Labeling Index; P < 0.0001), and shortened overall survival (P < 0.0001). For example, 8p deletion was seen in 32% of 290 grade 1, 43% of 438 grade 2, and 65% of 427 grade 3 cancers. In addition, 8p deletions were strongly linked to amplification of MYC (P < 0.0001), HER2 (P < 0.0001), and CCND1 (p = 0.001), but inversely associated with ER receptor expression (p = 0.0001). Remarkably, 46.5% of 8p-deleted cancers harbored amplification of at least one of the analyzed genes as compared to 27.5% amplifications in 8p-non-deleted cancers (P < 0.0001). In conclusion, 8p deletion characterizes a subset of particularly aggressive breast cancers. As 8p deletions are easy to analyze, this feature appears to be highly suited for future DNA based prognostic breast cancer panels. The strong link of 8p deletion with various gene amplifications raises the possibility of a role for regulating genomic stability.
U2 - 10.1080/15384047.2015.1046025
DO - 10.1080/15384047.2015.1046025
M3 - SCORING: Journal article
C2 - 25961141
VL - 16
SP - 1080
EP - 1087
JO - CANCER BIOL THER
JF - CANCER BIOL THER
SN - 1538-4047
IS - 7
ER -
