Overexpression of c-erbB-2 protein correlates with chromosomal gain at the c-erbB-2 locus and patient survival in advanced colorectal carcinomas.
Overexpression of the c-erbB-2 protein (also called HER-2/neu) is observed in a variety of malignancies including colorectal cancer (CRC). In this study we aimed to evaluate the rate of c-erbB-2 overexpression in our tumor collection and to clarify its correlation with the chromosomal status at the c-erbB-2 locus in CRC. Additionally we correlated the c-erbB-2 overexpression and the chromosomal gain of 17q with patient survival. Seventy-four specimens were analyzed immunohistochemically using a polyclonal c-erbB-2 antibody (DAKO) and the staining was scored according to the Clinical Trial Assay recommendations (0-3+). Of these, 45 cases were analyzed by comparative genomic hybridization (CGH) and immunohistochemistry (IHC). Overexpression was observed in 51% of the cases (score > or = 2). Chromosomal gains at the c-erbB-2 locus were clearly correlated with overexpression of the gene (P = 0.0009). Furthermore Kaplan-Meier analysis showed that overexpression of c-erbB-2 was significantly associated with poor survival and thus could serve as a prognostic marker. We conclude that c-erbB-2 is related with tumor progression in CRC which can be observed on protein level and reflects chromosomal gain at the locus at 17q.
Institute of Pathology, Charité-Campus Mitte, Berlin, Germany.
Thomas
T
Knösel
Youngwei
Y
Yu
Ulrike
U
Stein
Holger
H
Schwabe
Karsten
K
Schlüns
Peter Michael
PM
Schlag
Manfred
M
Dietel
Iver
I
Petersen
D022981:Allelic Imbalance; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics* / Q000648:ultrastructure; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D015993:Life Tables; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000502:physiology*; D016019:Survival Analysis
D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases