TY - JOUR
T1 - HER family receptor abnormalities in lung cancer brain metastases and corresponding primary tumors
AU - Sun, Menghong
AU - Behrens, Carmen
AU - Feng, Lei
AU - Ozburn, Natalie
AU - Tang, Ximing
AU - Yin, Guosheng
AU - Komaki, Ritsuko
AU - Varella-Garcia, Marileila
AU - Waun, Ki Hong
AU - Aldape, Kenneth D.
AU - Wistuba, Ignacio I.
PY - 2009/8/1
Y1 - 2009/8/1
N2 - Purpose: To compare the characteristics of deregulation of HERre ceptors and their ligands between primary tumor and corresponding brain metastases of non - small cell lung carcinoma (NSCLC). Experimental Design: Fifty-five NSCLC primary tumors and corresponding brain metastases specimens were examined for the immunohistochemical expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, Her2, Her3, and phosphorylated Her3, and their ligands EGF, transforming growth factor-a, amphiregulin, epiregulin, betacellulin, heparin-binding EGFR-like growth factor, neuregulin (NRG) 1, and NRG2. Analysis of EGFR copy number using fluorescence in situ hybridization and mutation by PCR-based sequencing was also done. Results: Metastases showed significantly higher immunohistochemical expression of EGF (membrane: brain metastases 66.0 versus primary tumors 48.5; P = 0.027; nucleus: brain metastases 92.2 versus 67.4; P = 0.008), amphiregulin (nucleus: brain metastases 53.7 versus primary tumors 33.7; P = 0.019), phosphorylated EGFR( membrane: brain metastases 161.5 versus primary tumors 76.0; P < 0.0001; cytoplasm: brainmetastases101.5 versus primary tumors 55.9; P = 0.014), and phosphorylated Her3 (membrane: brain metastases 25.0 versus primary tumors 3.7; P = 0.001) than primary tumors did. Primary tumors showed significantly higher expression of cytoplasmic transforming growth factor-α(primary tumors 149.8 versus brain metastases 111.3; P = 0.008) and NRG1 (primary tumors 158.5 versus brain metastases 122.8; P = 0.006). In adenocarcinomas, a similar high frequency of EGFR copy number gain (high polysomy and amplification) was detected in primary (65%) and brain metastasis (63%) sites. However, adenocarcinoma metastases (30%) showed higher frequency of EGFR amplification than corresponding primary tumors (10%). Patients whose primary tumors showed EGFR amplification tended to develop brainmetastases at an earlier time point. Conclusions: Our findings suggest that NSCLC brain metastases have some significant differences in HERf amily receptor - related abnormalities from primary lung tumors.
AB - Purpose: To compare the characteristics of deregulation of HERre ceptors and their ligands between primary tumor and corresponding brain metastases of non - small cell lung carcinoma (NSCLC). Experimental Design: Fifty-five NSCLC primary tumors and corresponding brain metastases specimens were examined for the immunohistochemical expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, Her2, Her3, and phosphorylated Her3, and their ligands EGF, transforming growth factor-a, amphiregulin, epiregulin, betacellulin, heparin-binding EGFR-like growth factor, neuregulin (NRG) 1, and NRG2. Analysis of EGFR copy number using fluorescence in situ hybridization and mutation by PCR-based sequencing was also done. Results: Metastases showed significantly higher immunohistochemical expression of EGF (membrane: brain metastases 66.0 versus primary tumors 48.5; P = 0.027; nucleus: brain metastases 92.2 versus 67.4; P = 0.008), amphiregulin (nucleus: brain metastases 53.7 versus primary tumors 33.7; P = 0.019), phosphorylated EGFR( membrane: brain metastases 161.5 versus primary tumors 76.0; P < 0.0001; cytoplasm: brainmetastases101.5 versus primary tumors 55.9; P = 0.014), and phosphorylated Her3 (membrane: brain metastases 25.0 versus primary tumors 3.7; P = 0.001) than primary tumors did. Primary tumors showed significantly higher expression of cytoplasmic transforming growth factor-α(primary tumors 149.8 versus brain metastases 111.3; P = 0.008) and NRG1 (primary tumors 158.5 versus brain metastases 122.8; P = 0.006). In adenocarcinomas, a similar high frequency of EGFR copy number gain (high polysomy and amplification) was detected in primary (65%) and brain metastasis (63%) sites. However, adenocarcinoma metastases (30%) showed higher frequency of EGFR amplification than corresponding primary tumors (10%). Patients whose primary tumors showed EGFR amplification tended to develop brainmetastases at an earlier time point. Conclusions: Our findings suggest that NSCLC brain metastases have some significant differences in HERf amily receptor - related abnormalities from primary lung tumors.
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U2 - 10.1158/1078-0432.CCR-08-2921
DO - 10.1158/1078-0432.CCR-08-2921
M3 - Article
C2 - 19622585
AN - SCOPUS:68049147562
SN - 1078-0432
VL - 15
SP - 4829
EP - 4837
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 15
ER -