PMID- 11595720
OWN - NLM
STAT- MEDLINE
DCOM- 20011205
LR  - 20221207
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 7
IP  - 10
DP  - 2001 Oct
TI  - Expression of Her-2/neu in human lung cancer cell lines by immunohistochemistry 
      and fluorescence in situ hybridization and its relationship to in vitro 
      cytotoxicity by trastuzumab and chemotherapeutic agents.
PG  - 3239-50
AB  - Overexpression of the Her-2/neu oncogene and receptor protein was reported in 
      approximately 20% of breast cancers and was associated with a poor prognosis. 
      Her-2/neu expression was a predictor for response to trastuzumab, a monoclonal 
      antibody that recognizes the Her-2/neu cell surface receptor. Data regarding the 
      expression of Her-2/neu in lung cancer are far more limited, and there is little 
      information regarding the influence of Her-2/neu expression and response to 
      trastuzumab alone or in combination with chemotherapeutic agents. In this report 
      we evaluated Her-2/neu gene expression by fluorescence in situ hybridization 
      (FISH) and the cell surface expression of the Her-2/neu receptor by 
      immunohistochemistry using the HercepTest and by FACS analysis in 31 lung cancer 
      cell lines with 5 breast cancer cell lines as controls. By FACS, we found 
      Her-2/neu overexpression (mean fluorescence intensity >8) in 2 of the 22 
      non-small cell lung cancer (NSCLC) cell lines (9%), none of 11 small cell lung 
      cancer (SCLC) cell lines, and 4 of 5 breast cancer cell lines. A positive 
      HercepTest (2+ or 3+) was found in 6 of 19 NSCLC cell lines (26%, 2+; 5%, 3+), 1 
      of 3 SCLC cell lines (33%), and 4 of 5 breast cancer cell lines (80%). One of 6 
      NSCLC cell lines examined (17%) had gene amplification with >32 copies of 
      Her-2/neu/cell and had homogeneous staining regions. One NSCLC cell line had a 
      maximum of 14 copies of Her-2/neu/cell, and 3 had modest increases in Her-2/neu 
      gene copy number without gene amplification (maximum 5-8 copies/cell). None of 
      the SCLC cell lines had more than a maximum of 4 copies/cell, whereas the 2 
      breast cancer cell lines had maximum Her-2/neu copy numbers of 80 and 5, 
      respectively. Aneusomy rather than true amplification was the major cause of 
      increased Her-2/neu expression in most of the NSCLC cell lines. There was a 
      strong correlation when the results of fluorescence-activated cell sorter, 
      HercepTest results, and FISH were compared in pairs. Furthermore, Trastuzumab 
      produced a G(1) cell cycle arrest and growth inhibition only in cell lines 
      expressing Her-2/neu. The IC(50) for growth inhibition was correlated with cell 
      surface Her-2/neu expression. The combination of trastuzumab and chemotherapeutic 
      agents produced more than additive growth inhibition in cell lines expressing 
      Her-2/neu, but the level of additivity was not related to the amount of Her-2/neu 
      expression. These data indicate that trastuzumab alone and in combination with 
      chemotherapeutic agents should be tested in NSCLC patients and that Her-2/neu 
      should be assessed by both immunohistochemistry and FISH methods in these studies 
      to determine which test is the best predictor of outcome.
FAU - Bunn, P A Jr
AU  - Bunn PA Jr
AD  - Lung Cancer Program, Department of Medicine, University of Colorado Cancer 
      Center, 4200 East Ninth Avenue, Denver CO 80262, USA.
FAU - Helfrich, B
AU  - Helfrich B
FAU - Soriano, A F
AU  - Soriano AF
FAU - Franklin, W A
AU  - Franklin WA
FAU - Varella-Garcia, M
AU  - Varella-Garcia M
FAU - Hirsch, F R
AU  - Hirsch FR
FAU - Baron, A
AU  - Baron A
FAU - Zeng, C
AU  - Zeng C
FAU - Chan, D C
AU  - Chan DC
LA  - eng
GR  - CA 46934-09/CA/NCI NIH HHS/United States
GR  - CA 58187-04/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 5V9KLZ54CY (Vinblastine)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
RN  - P88XT4IS4D (Paclitaxel)
RN  - Q20Q21Q62J (Cisplatin)
RN  - Q6C979R91Y (Vinorelbine)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/*pharmacology
MH  - Carcinoma, Non-Small-Cell Lung/genetics/metabolism/pathology
MH  - Cell Cycle/drug effects
MH  - Cell Division/*drug effects
MH  - Cisplatin/pharmacology
MH  - Deoxycytidine/*analogs & derivatives/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/genetics/metabolism/pathology
MH  - Paclitaxel/pharmacology
MH  - Receptor, ErbB-2/analysis/*genetics/immunology
MH  - Trastuzumab
MH  - Tumor Cells, Cultured
MH  - Vinblastine/*analogs & derivatives/pharmacology
MH  - Vinorelbine
MH  - Gemcitabine
EDAT- 2001/10/12 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/12 10:00
PHST- 2001/10/12 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/12 10:00 [entrez]
PST - ppublish
SO  - Clin Cancer Res. 2001 Oct;7(10):3239-50.