PMID- 14502781
OWN - NLM
STAT- MEDLINE
DCOM- 20031028
LR  - 20141120
IS  - 0022-4790 (Print)
IS  - 0022-4790 (Linking)
VI  - 84
IP  - 2
DP  - 2003 Oct
TI  - Absence of HER2 overexpression in metastatic malignant melanoma.
PG  - 82-8
AB  - BACKGROUND AND OBJECTIVES: Currently available systemic therapies for malignant 
      melanoma produce low response rates in patients, and more effective treatment 
      modalities are clearly needed. Trastuzumab (Herceptin), the antibody to the HER2 
      oncoprotein, has had a significant impact on therapy for patients with 
      HER2-overexpressing metastatic breast cancer. This study examined the incidences 
      of HER2 protein overexpression and HER2 gene amplification in metastatic 
      malignant melanoma, which remain unclear in the literature. METHODS: The study 
      evaluated patients with stage III and stage IV malignant melanoma who were 
      treated between 1983 and 1999. Tissue blocks were retrieved and reviewed to 
      confirm the diagnosis. From the 101 cases identified, 49 (31 stage III and 18 
      stage IV) had sufficient residual tumor sample to enable an assay to be 
      performed. The blocks were tested for HER2 overexpression using the DAKO 
      HercepTest immunohistochemical (IHC) assay. Any sample that tested 1+ or greater 
      for HER2 expression on IHC and a randomly selected subset of HER2-negative 
      samples were tested for the presence of HER2 gene amplification using the Vysis 
      PathVysion fluorescence in situ hybridization (FISH) assay. RESULTS: The median 
      age of the 49 selected patients was 52.2 years, and the male-to-female ratio was 
      1.23:1 (27 men to 22 women). All of the 49 cases of malignant melanoma were 
      negative for HER2 overexpression by IHC. However, two samples (3%) were found to 
      have a weak level of HER2 expression (1+ level of staining). Subsequent FISH 
      results on the samples that were 1+ on IHC were negative for HER2 gene 
      amplification. FISH results on 21 other randomly selected IHC-negative samples 
      were also negative for HER2 amplification. Flow cytometry failed to show HER2 
      overexpression in two melanoma cell lines, and treatment of these cells with 
      trastuzumab did not affect their proliferation rate. CONCLUSIONS: We found a low 
      incidence of HER2 expression and no evidence of HER2 protein overexpression or 
      HER2 gene amplification in metastatic malignant melanoma tissues. Therefore, 
      routine testing for HER2 overexpression or HER2 amplification would not be of 
      benefit in this patient population. These results also imply that anti-HER2 
      therapy with trastuzumab is highly unlikely to provide benefit for patients with 
      metastatic melanoma.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Inman, J Lucas
AU  - Inman JL
AD  - Department of General Surgery, Wake Forest University, Winston-Salem, North 
      Carolina 27157, USA.
FAU - Kute, Tim
AU  - Kute T
FAU - White, Wain
AU  - White W
FAU - Pettenati, Mark
AU  - Pettenati M
FAU - Levine, Edward A
AU  - Levine EA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Surg Oncol
JT  - Journal of surgical oncology
JID - 0222643
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Breast Neoplasms/metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Gene Amplification
MH  - Gene Expression Regulation, Neoplastic
MH  - *Genes, erbB-2
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Melanoma/*genetics/*metabolism/pathology
MH  - Prospective Studies
MH  - Receptor, ErbB-2/*biosynthesis
MH  - Tumor Cells, Cultured
EDAT- 2003/09/23 05:00
MHDA- 2003/10/29 05:00
CRDT- 2003/09/23 05:00
PHST- 2003/09/23 05:00 [pubmed]
PHST- 2003/10/29 05:00 [medline]
PHST- 2003/09/23 05:00 [entrez]
AID - 10.1002/jso.10297 [doi]
PST - ppublish
SO  - J Surg Oncol. 2003 Oct;84(2):82-8. doi: 10.1002/jso.10297.