Yuichi Fujimoto1, Shinsaku Togo1, Miniwan Tulafu1, Kazue Shimizu1, Takuo Hayashi2, Toshimasa Uekusa3, Yuichirou Honma1, Yukiko Namba1, Kazuya Takamochi4, Shiaki Oh4, Kenji Suzuki4, Kazuhisa Takahashi1. 1. Department of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan ; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan. 2. Department of Pathology, Juntendo University School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan. 3. Department of Pathology, Labor Health and Welfare Organization Kanto Rosai Hospital 1-1 Kizukisumiyoshi-cho, Nakahara-Ku, Kawasaki, Kanagawa Prefecture 211-8510, Japan. 4. Department of General Thoracic Surgery, Juntendo University School of Medicine 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
Abstract
BACKGROUND: Lung adenocarcinoma is often composed of a complex and heterogeneous mixture of histological subtypes. Invasive adenocarcinomas are now classified by their predominant pattern, using the comprehensive histological subtyping of the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS) classifications. This study aimed to determine whether the expression levels of predictive chemotherapy biomarkers are associated with the histological subtypes proposed by the IASLC/ATS/ERS classification. MATERIALS AND METHODS: We reviewed data on representative tissue samples from 27 patients who received surgical resection and the expression of excision repair cross complementation group 1 (ERCC1), class III β-tubulin, thymidylate synthase (TS), ribonucleotide reductase M1 (RRM1), and c-Met were examined using immunostaining on tumor tissue slides. We assessed immunohistochemical H-scores, as calculated from the intensity and distribution of intratumor expression, according to the IASLC/ATS/ERS histological subtype. RESULTS: The expression levels of predictive chemotherapy biomarkers varied according to histological subtype. The H-scores of TS and class III β-tubulin expression levels were higher in solid-type components than they were in lepidic-type components Tumors with solid predominant histology tended to recur earlier than non-solid predominant tumors. However, none of the H-scores in histologically predominant tissues was significantly associated with staging or overall survival. CONCLUSIONS: Immunohistochemical H-scores of the predictive chemotherapy biomarkers were strongly associated with histological subtype. The presence of a solid subtype, which was associated with poor outcomes, might be assessed by measuring these biomarkers in mixed subtype adenocarcinomas.
BACKGROUND:Lung adenocarcinoma is often composed of a complex and heterogeneous mixture of histological subtypes. Invasive adenocarcinomas are now classified by their predominant pattern, using the comprehensive histological subtyping of the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS) classifications. This study aimed to determine whether the expression levels of predictive chemotherapy biomarkers are associated with the histological subtypes proposed by the IASLC/ATS/ERS classification. MATERIALS AND METHODS: We reviewed data on representative tissue samples from 27 patients who received surgical resection and the expression of excision repair cross complementation group 1 (ERCC1), class III β-tubulin, thymidylate synthase (TS), ribonucleotide reductase M1 (RRM1), and c-Met were examined using immunostaining on tumor tissue slides. We assessed immunohistochemical H-scores, as calculated from the intensity and distribution of intratumor expression, according to the IASLC/ATS/ERS histological subtype. RESULTS: The expression levels of predictive chemotherapy biomarkers varied according to histological subtype. The H-scores of TS and class III β-tubulin expression levels were higher in solid-type components than they were in lepidic-type components Tumors with solid predominant histology tended to recur earlier than non-solid predominant tumors. However, none of the H-scores in histologically predominant tissues was significantly associated with staging or overall survival. CONCLUSIONS: Immunohistochemical H-scores of the predictive chemotherapy biomarkers were strongly associated with histological subtype. The presence of a solid subtype, which was associated with poor outcomes, might be assessed by measuring these biomarkers in mixed subtype adenocarcinomas.
Entities:
Keywords:
Class III β-tubulin; Thymidylate synthase; c-Met; excision repair cross complementation group 1; immunohistochemistry; ribonucleotide reductase M1
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