HER-2 and HER-3 expression in liver metastases of patients with colorectal cancer.
OBJECTIVE
In this study, we evaluate the frequency of HER-2 and HER-3 expression in liver metastases from patients with colorectal cancer (CRLM). We analyzed the potential of HER-2 and HER-3 as therapeutic targets and evaluated their prognostic value.


METHODS
Overall 208 patients with CRLM were enrolled. HER-2 and HER-3 expression were determined in metastatic tissue of diagnostic punch biopsies (n = 29) or resection specimens (n = 179). The results of immunohistochemistry (IHC) scoring and In-situ-hybridization (ISH)-amplification were correlated with clinical parameters and for the 179 resected patients with cancer-specific (CSS) and overall survival (OS). The mean follow-up time was 56.7 months.


RESULTS
Positivity of HER-2 status (IHC score 2+/ISH+ and IHC 3+) was found in 8.2% of CRLM. High expression of HER-3 (IHC score 2+ and IHC 3+) was detected in 75.0% of liver metastases. CSS after liver surgery was determined and was independent from the HER-2 status (p = 0.963); however HER-3 was prognostic with a favorable course for patients showing an overexpression of HER-3 (p = 0.037).


CONCLUSIONS
HER-2 overexpression occurs in only 8% of patients with CRLM but with 75% of cases HER-3 is frequently overexpressed in CRLM. Therefore, HER-2 and particularly HER-3 could serve as novel targets to be addressed within multimodal treatment approaches.
Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany.
Hanna
H
Styczen
Targos Molecular Pathology, Pathology Nordhessen, Kassel, Germany.
Iris
I
Nagelmeier
Department of Medical Statistics, University Medical Center, Göttingen, Germany.
Tim
T
Beissbarth
Department of Medical Statistics, University Medical Center, Göttingen, Germany.
Manuel
M
Nietert
Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany.
Kia
K
Homayounfar
Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany.
Thilo
T
Sprenger
Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany.
Ute
U
Boczek
Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany.
Kathrin
K
Stanek
Department of Pathology, University Medical Center, Göttingen, Germany.
Julia
J
Kitz
Department of Radiotherapy and Radiooncology, University Medical Center, Göttingen, Germany.
Hendrik A
HA
Wolff
Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany.
B Michael
BM
Ghadimi
Targos Molecular Pathology, Pathology Nordhessen, Kassel, Germany.
Peter
P
Middel
Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany.
Torsten
T
Liersch
Targos Molecular Pathology, Pathology Nordhessen, Kassel, Germany.
Josef
J
Rüschoff
Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany.
Lena-Christin
LC
Conradi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003106:Colon / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D020893:Receptor, ErbB-3 / Q000096:biosynthesis / Q000235:genetics*; D012007:Rectum / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome
D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C508053:ERBB2 protein, human
HER-2; HER-3; colorectal cancer; liver metastases; targeted therapy