TY - JOUR
T1 - Heterogeneity of EGFR aberrations and correlation with histological structures
T2 - Analyses of therapy-naive isogenic lung cancer lesions with EGFR mutation
AU - Suda, Kenichi
AU - Murakami, Isao
AU - Yu, Hui
AU - Ellison, Kim
AU - Shimoji, Masaki
AU - Genova, Carlo
AU - Rivard, Christopher J.
AU - Mitsudomi, Tetsuya
AU - Hirsch, Fred R.
N1 - Publisher Copyright:
© 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
PY - 2016
Y1 - 2016
N2 - Introduction: EGFR gene somatic mutation is reportedly homogeneous. However, there are few data regarding the heterogeneity of expression of mutant EGFR protein and EGFR gene copy number, especially in extrathoracic lesions. These types of data may enhance our understanding of the biology of EGFR-mutated lung cancer and our understanding of the heterogeneous response patterns to EGFR TKIs. Methods: An 81-year-old never-smoking female with lung adenocarcinoma could not receive any systemic therapy because of her poor performance status. After her death, 15 tumor specimens from different sites were obtained by autopsy. Expression of mutant EGFR protein and EGFR gene copy numbers were assessed by immunohistochemical analysis and by silver in situ hybridization, respectively. Heterogeneity in these EGFR aberrations was compared between metastatic sites (distant versus lymph node) or histological structures (micropapillary versus nonmicropapillary). Results: All lesions showed positive staining for mutant EGFR protein, except for 40% of the papillary component in one of the pulmonary metastases (weak staining below the 1+ threshold). Expression of mutant-specific EGFR protein, evaluated by H-score, was significantly higher in the micropapillary components than in the nonmicropapillary components (Mann-Whitney U test, p = 0.014). EGFR gene copy number was quite different between lesions but not correlated with histological structure or metastatic form. However, EGFR gene copy numbers were similar between histological structures in each lesion. Conclusion: These data indicate that expression of EGFR mutant protein and EGFR gene copy number do not change as a consequence of tumor progression. This also justifies using the biopsy specimens from metastases as a surrogate for primary tumors.
AB - Introduction: EGFR gene somatic mutation is reportedly homogeneous. However, there are few data regarding the heterogeneity of expression of mutant EGFR protein and EGFR gene copy number, especially in extrathoracic lesions. These types of data may enhance our understanding of the biology of EGFR-mutated lung cancer and our understanding of the heterogeneous response patterns to EGFR TKIs. Methods: An 81-year-old never-smoking female with lung adenocarcinoma could not receive any systemic therapy because of her poor performance status. After her death, 15 tumor specimens from different sites were obtained by autopsy. Expression of mutant EGFR protein and EGFR gene copy numbers were assessed by immunohistochemical analysis and by silver in situ hybridization, respectively. Heterogeneity in these EGFR aberrations was compared between metastatic sites (distant versus lymph node) or histological structures (micropapillary versus nonmicropapillary). Results: All lesions showed positive staining for mutant EGFR protein, except for 40% of the papillary component in one of the pulmonary metastases (weak staining below the 1+ threshold). Expression of mutant-specific EGFR protein, evaluated by H-score, was significantly higher in the micropapillary components than in the nonmicropapillary components (Mann-Whitney U test, p = 0.014). EGFR gene copy number was quite different between lesions but not correlated with histological structure or metastatic form. However, EGFR gene copy numbers were similar between histological structures in each lesion. Conclusion: These data indicate that expression of EGFR mutant protein and EGFR gene copy number do not change as a consequence of tumor progression. This also justifies using the biopsy specimens from metastases as a surrogate for primary tumors.
KW - Autopsy
KW - Lung adenocarcinoma
KW - Micropapillary
KW - Mutant-specific antibody
KW - Silver in situ hybridization
UR - http://www.scopus.com/inward/record.url?scp=84991045039&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2016.05.017
DO - 10.1016/j.jtho.2016.05.017
M3 - Article
C2 - 27257133
AN - SCOPUS:84991045039
SN - 1556-0864
VL - 11
SP - 1711
EP - 1717
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 10
ER -