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T. Shigenobu
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OA10 - EGFR Mutations (ID 382)
- Event: WCLC 2016
- Type: Oral Session
- Track: Biology/Pathology
- Presentations: 1
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OA10.05 - EGFR Gene Mutations Affect Tumor-Infiltrating Stromal Cell Components in Early-Stage Lung Adenocarcinoma (ID 6305)
11:45 - 11:55 | Author(s): T. Shigenobu
- Abstract
- Presentation
Background:
Tumors are complex structures consisting of cancer cells surrounded by a tumor stroma that is now recognized to be critical for cancer progression. Although epidermal growth factor receptor (EGFR) mutations are frequently observed in non-small cell lung carcinoma, it remains poorly understood whether EGFR mutations in cancer cells affect the tumor stroma. In this study, we studied the status of EGFR mutations in early-stage lung adenocarcinoma and analyzed the relations of EGFR mutations to tumor-infiltrating stromal cell components.
Methods:
A total of 152 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete tumor resection in Keio University Hospital between 2010 and 2014 were studied. Genomic DNA was isolated from formalin-fixed, paraffin-embedded tumor sections and mutational analyses of EGFR gene exons 19, 20 and 21 were performed by a polymerase chain reaction-based method. Paraffin sections were also subjected to immunohistochemistry for CD3, FOXP3, CD163 or CD204. Numbers of CD3-, FOXP3-, CD163- or CD204-immunostained cells were counted by observing 5 different fields at x200 magnification.
Results:
EGFR mutations were detected in 71 (47%) of the 152 patients with clinical stage IA lung adenocarcinoma and were found more frequently in women and non-smokers. These contained 38 patients with missense mutations in exon 21 (L858R) and 30 patients with deletions in exon 19. By immunohistochemistry, the number of stromal macrophages positive for CD163 or CD204, markers for tumor-associated macrophages (TAMs), was significantly decreased within tumors with EGFR mutations compared to within those with wild-type EGFR, whereas the number of CD3[+] T cells or FOXP3[+] regulatory T cells was comparable between these groups. Both tumors with missense mutations in exon 21 and deletions in exon 19 had a similar trend toward decreased TAMs in the tumor stroma.
Conclusion:
Our data suggest that EGFR mutations in early-stage lung adenocarcinoma are associated with decreased TAMs in the tumor stroma. EGFR mutation status might act on not only cancer cell behavior but tumor microenvironment.
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