TY - JOUR
T1 - Terminal respiratory unit type lung adenocarcinoma is associated with distinctive EGFR immunoreactivity and EGFR mutations
AU - Peterson, Michael R.
AU - Piao, Zhe
AU - Bazhenova, Lyudmila A.
AU - Weidner, Noel
AU - Yi, Eunhee S.
PY - 2007/9
Y1 - 2007/9
N2 - Approximately 10% to 20% of nonsmall cell lung cancer patients respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as gefitinib. Responders are mostly nonsmokers and women with tumors displaying bronchioloalveolar features. Mutations of the tyrosine kinase domain of the EGFR gene have been associated with a clinical response to gefitinib. A recent study reported that the terminal respiratory unit (TRU)-type adenocarcinoma shares the clinical profile and EGFR mutations of gefitinib responders. EGFR immunoreactivity in this context has not been reported in the literature. We performed a detailed immunohistochemical analysis of EGFR expression on 124 consecutive lung resection specimens for malignancy, to survey the EGFR immunoreactivity in lung cancers in general and to correlate EGFR immunoreactivity with EGFR mutations and TRU-type histology. EGFR positivity was seen most frequently in squamous cell carcinomas (77%), followed by TRU-type adenocarcinomas (63%), large cell carcinomas (23%), and non-TRU-type adenocarcinomas (12%). A distinctive basally oriented cytoplasmic positivity was observed exclusively in TRU-type adenocarcinomas. EGFR mutation was identified in 6 of 54 cases studied and all 6 cases were TRU-type adenocarcinomas. Five of six cases with EGFR mutation were positive for EGFR immunostain with the basal cytoplasmic localization. In conclusion, EGFR immunoreactivity with basal cytoplasmic pattern was exclusively seen in TRU-type adenocarcinoma and a subset of these cases was seen with EGFR mutations in the responders to EGFR inhibitor therapy.
AB - Approximately 10% to 20% of nonsmall cell lung cancer patients respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as gefitinib. Responders are mostly nonsmokers and women with tumors displaying bronchioloalveolar features. Mutations of the tyrosine kinase domain of the EGFR gene have been associated with a clinical response to gefitinib. A recent study reported that the terminal respiratory unit (TRU)-type adenocarcinoma shares the clinical profile and EGFR mutations of gefitinib responders. EGFR immunoreactivity in this context has not been reported in the literature. We performed a detailed immunohistochemical analysis of EGFR expression on 124 consecutive lung resection specimens for malignancy, to survey the EGFR immunoreactivity in lung cancers in general and to correlate EGFR immunoreactivity with EGFR mutations and TRU-type histology. EGFR positivity was seen most frequently in squamous cell carcinomas (77%), followed by TRU-type adenocarcinomas (63%), large cell carcinomas (23%), and non-TRU-type adenocarcinomas (12%). A distinctive basally oriented cytoplasmic positivity was observed exclusively in TRU-type adenocarcinomas. EGFR mutation was identified in 6 of 54 cases studied and all 6 cases were TRU-type adenocarcinomas. Five of six cases with EGFR mutation were positive for EGFR immunostain with the basal cytoplasmic localization. In conclusion, EGFR immunoreactivity with basal cytoplasmic pattern was exclusively seen in TRU-type adenocarcinoma and a subset of these cases was seen with EGFR mutations in the responders to EGFR inhibitor therapy.
KW - Adenocarcinoma
KW - EGFR
KW - Gefitinib
KW - Immunohistochemistry
KW - Lung
KW - Terminal respiratory unit
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UR - http://www.scopus.com/inward/citedby.url?scp=34548242808&partnerID=8YFLogxK
U2 - 10.1097/PAI.0b013e31802d1590
DO - 10.1097/PAI.0b013e31802d1590
M3 - Article
C2 - 17721266
AN - SCOPUS:34548242808
SN - 1541-2016
VL - 15
SP - 242
EP - 247
JO - Applied Immunohistochemistry and Molecular Morphology
JF - Applied Immunohistochemistry and Molecular Morphology
IS - 3
ER -