Establish of new deteciton of EGFR mutation status using immunostaining in non-small cell lung cancer

2013 Fiscal Year Final Research Report

• Project/Area Number: 23790425
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Kurume University
• Principal Investigator: KAWAHARA Akihiko 久留米大学, 大学病院, 臨床検査技師 (00469347)
• Project Period (FY): 2011 – 2013
• Keywords: 病理学 / 免疫染色 / EGFR遺伝子変異抗体

Research Abstract

To establish a testing algorithm for EGFR mutation status in NSCLC patients, we utilized PNA-LNA PCR clamp assay and immunostaining. In the 133 samples, positive, negative and equivocal results for EGFR mutation-specific antibodies were observed in 37 patients (27.8%), 85 patients (63.9%) and 11 patients (8.3%), respectively. Thirty-seven patients showed positive EGFR expression by immunostaining, and 35 (94.6%) of these also tested positive in the DNA-based assay. Of 85 EGFR-negative patients by immunostaining, 77 (90.6%) also tested negative in the DNA-based assay. In NSCLC patients treated with EGFR-TKIs, the progression-free survival after the start of EGFR-TKIs treatment was significantly longer in patients with EGFR positive expression than in those with equivocal and negative expression (P = 0.002). Our results suggest immunostaining for EGFR mutation-specific antibodies are a new test for EGFR-TKI inhibition and could be a useful indicator with regard to patient management.

Research Products

• [Journal Article] Erlotinib resistance in lung cancer cells mediated by integrinβ1/Src/Akt-driven bypass signaling (2013)
  • Author(s): Kanda R, Kawahara A, Watari K, Murakami Y, Sonoda K, Maeda M, Fujita H, Kage M, Uramoto H, Costa C, Kuwano M, Ono M
  • Journal Title: Cancer Res Volume: 73巻 Pages: 6243-6253
  • DOI: 10.1158/0008-5472.CAN-12-4502
  • Peer Reviewed
• [Journal Article] Prognostic Value of EGFR Mutation and ERCC1 in Patients with Non-Small Cell Lung Cancer Undergoing Platinum-Based Chemotherapy (2013)
  • Author(s): Yamashita F, Azuma K, Yoshida T, Yamada K, Kawahara A, Hattori S, Takeoka H, Zaizen Y, Kawayama T, Kage M, Hoshino T
  • Journal Title: PLoS One Volume: 8巻 Pages: e71356
  • DOI: 10.1371/journal.pone.0071356
  • Peer Reviewed
• [Journal Article] Comparison of adverse events and efficacy between gefitinib and erlotinib in patients with non-small-cell lung cancer : a retrospective analysis (2013)
  • Author(s): Yoshida T, Yamada K, Azuma K, Kawahara A, Abe H, Hattori S, Yamashita F, Zaizen Y, Kage M, Hoshino T
  • Journal Title: Med Oncol Volume: 30巻 Pages: 349
  • DOI: 10.1007/s12032-012-0349-y
  • Peer Reviewed
• [Journal Article] 液状細胞診にて診断した気管支腺原発の粘表皮癌の1例 (2013)
  • Author(s): 福満千容,河原明彦,山口知彦,安倍秀幸,多比良朋希,高瀬頼妃呼,秋葉純,鹿毛政義
  • Journal Title: 日本臨床細胞学雑誌 Volume: 52巻 Pages: 473-477
  • DOI: 10.5795/jjscc.52.473
  • Peer Reviewed
• [Journal Article] A diagnostic algorithm using EGFR mutation-specific antibodies for rapid response EGFR-TKI treatment in patients with non-small cell lung cancer (2012)
  • Author(s): Kawahara A, Taira T, Azuma K, Tominaga M, Hattori S, Kawahara M, Abe H, Yamaguchi T, Akiba J, Takamori S, Hayashi A, Kage M
  • Journal Title: Lung Cancer Volume: 78巻 Pages: 39-44
  • DOI: 10.1016/j.lungcan.2012.07.002
  • Peer Reviewed
• [Journal Article] 乳癌肺転移との鑑別を要したEGFR遺伝子変異を伴う原発性肺癌の1例 (2012)
  • Author(s): 河原明彦,山口知彦,安倍秀幸,多比良朋希,吉田友子,内藤嘉紀,秋葉純,鹿毛政義
  • Journal Title: 日本臨床細胞学会雑誌 Volume: 51巻 Pages: 120-124
  • DOI: 10.5795/jjscc.51.120
  • Peer Reviewed
• [Journal Article] Chemotherapy for non-small cell lung cancer complicated by idiopathic interstitial pneumonia (2012)
  • Author(s): Kinoshita T, Azuma K, Sasada T, Okamoto M, Hattori S, Imamura Y, Yamada K, Tajiri M, Yoshida T, Zaizen Y, Kawahara A, Fujimoto K, Hoshino T
  • Journal Title: Oncol Lett Volume: 4巻 Pages: 477-482
  • DOI: 10.3892/ol.2012.753
  • Peer Reviewed
• [Journal Article] Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy (2012)
  • Author(s): Zaizen Y, Azuma K, Kurata S, Sadashima E, Hattori S, Sasada T, Imamura Y, Kaida H, Kawahara A, Kinoshita T, Ishibashi M, Hoshino T
  • Journal Title: Eur J Radiol Volume: 81巻 Pages: 4179-4184
  • DOI: 10.1016/j.ejrad.2012.07.009
  • Peer Reviewed
• [Journal Article] Loss of Activating EGFR Mutant Gene Contributes to Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in Lung Cancer Cells (2012)
  • Author(s): Tabara K, Kanda R, Sonoda K, Kubo T, Murakami Y, Kawahara A, Azuma K, Abe H, Kage M, Yoshinaga A, Tahira T, Hayashi K, Arao T, Nishio K, Rosell R, Kuwano M, Ono M
  • Journal Title: PLoS One Volume: 7巻 Pages: e41017
  • DOI: 10.1371/journal.pone.0041017
  • Peer Reviewed
• [Journal Article] NDRG1/Cap43/Drg-1 may Predict Tumor Angiogenesis and Poor Outcome in Patients with Lung Cancer (2012)
  • Author(s): Azuma K, Kawahara A, Hattori S, Taira T, Tsurutani J, Watari K, Shibata T, Murakami Y, Takamori S, Ono M, Izumi H, Kage M, Yanagawa T, Nakagawa K, Hoshino T, Kuwano M
  • Journal Title: J Thorac Oncol Volume: 7巻 Pages: 779-789
  • DOI: 10.1097/JTO.0b013e31824c92b4
  • Peer Reviewed
• [Journal Article] Immunological evaluation of personalized peptide vaccination in refractory small cell lung cancer (2012)
  • Author(s): Terazaki Y, Yoshiyama K, Matsueda S, Watanabe N, Kawahara A, Naito Y, Suekane S, Komatsu N, Ioji T, Yamada A, Mine T, Terasaki M, Itoh K, Takamori S, Sasada T
  • Journal Title: Cancer Sci Volume: 103巻 Pages: 638-644
  • DOI: 10.1111/j.1349-7006.2012.02202.x
  • Peer Reviewed
• [Journal Article] Association of the Expression of Mutant Epidermal Growth Factor Receptor Protein as Determined with Mutation-Specific Antibodies in Non-small Cell Lung Cancer with Progression-Free Survival after Gefitinib Treatment (2012)
  • Author(s): Azuma K, Okamoto I, Kawahara A, Taira T, Nakashima K, Hattori S, Kinoshita T, Takeda M, Nakagawa K, Takamori S, Kuwano M, Ono M, Kage M
  • Journal Title: J Thorac Oncol Volume: 7巻 Pages: 122-127
  • DOI: 10.1097/JTO.0b013e31822eeba2
  • Peer Reviewed
• [Journal Article] Identification of non-small-cell lung cancer with activating EGFR mutations in malignant effusion and cerebrospinal fluid : Rapid and sensitive detection of exon 19 deletion E746-A750 and exon 21 L858R mutation by immunocytochemistry (2011)
  • Author(s): Kawahara A, Azuma K, Sumi A, Taira T, Nakashima K, Aikawa E, Abe H, Yamaguchi T, Takamori S, Akiba J, Kage M
  • Journal Title: Lung Cancer Volume: 74巻 Pages: 35-40
  • DOI: 10.1016/j.lungcan.2011.02.002
  • Peer Reviewed
• [Journal Article] Comparison of the expression levels of napsin A, thyroid transcription factor-1, and p63 in nonsmall cell lung cancer using cytocentrifuged bronchial brushings (2011)
  • Author(s): Aikawa E, Kawahara A, Hattori S, Yamaguchi T, Abe H, Taira T, Azuma K, Kage M
  • Journal Title: Cancer Cytopathol Volume: 119巻 Pages: 335-340
  • DOI: 10.1002/cncy.20162
  • Peer Reviewed
• [Presentation] Integrin beta1/Src/Akt-driven Bypass Signaling Pathway confers EGFR-TKI Resistance in Lung Cancer Cells (2013)
  • Author(s): Mayumi Ono, Rina Kanda, Kosuke Watari, Kahori Sonoda, Masashi, Maeda, Yuichi Murakami, Akihiko Kawahara, Masayoshi Kage, Hidetaka Uramoto, Michihiko Kuwano
  • Organizer: 72th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
  • Year and Date: 2013-10-03
• [Presentation] A case of EML4-ALK-positive lung adenocarcinoma with signet-ring cells (2013)
  • Author(s): Akihiko Kawahara, Tomoki Taira, Tomohiko Yamaguchi, Hideyuki Abe, Tomoko Yoshida, Yorihiko Takase, Chihiro Fukumitsu, Jun Akiba, Kage Masayoshi
  • Organizer: The 12^<th > Korea-Japan Joint Meeting for Diagnostic Cytopathology
  • Place of Presentation: 韓国
  • Year and Date: 2013-09-07
• [Presentation] Integrinβ1/Akt経路活性化を介した肺癌における新規エルロチニブ耐性獲得メカニズム (2013)
  • Author(s): 神田利奈,渡公祐,河原明彦,鹿毛政義,浦本秀隆,岡本勇,中川和彦,桑野信彦,小野眞弓
  • Organizer: 第17回日本がん分子標的治療学会
  • Place of Presentation: 京都
  • Year and Date: 2013-06-13
• [Presentation] 液状気管支細胞診を用いた肺癌診断 (2013)
  • Author(s): 福満千容,河原明彦,多比良朋希,山口知彦,安倍秀幸,吉田友子,髙瀨頼妃呼,秋葉純,谷川健,鹿毛政義
  • Organizer: 第54回日本臨床細胞学会総会
  • Place of Presentation: 東京
  • Year and Date: 2013-06-02
• [Presentation] LBCを用いた気管支擦過細胞診の現状.肺癌治療における細胞診の役割 (2013)
  • Author(s): 河原明彦
  • Organizer: 中四国実践セミナー
  • Place of Presentation: 愛媛
  • Year and Date: 2013-03-09
• [Presentation] 液状検体における細胞診の役割と遺伝子診断 (2012)
  • Author(s): 河原明彦,多比良朋希,山口知彦,安倍秀幸,吉田友子,髙瀨頼妃呼,福満千容,秋葉純,鹿毛政義
  • Organizer: 第51回日本臨床細胞学会秋期大会
  • Place of Presentation: 新潟
  • Year and Date: 2012-11-10
• [Presentation] 液状細胞診にて診断した気管支原発粘表皮癌の1例 (2012)
  • Author(s): 福満千容,河原明彦,山口知彦,安倍秀幸,多比良朋希,吉田友子,髙瀨頼妃呼,秋葉純,鹿毛政義
  • Organizer: 第51回日本臨床細胞学会秋期大会
  • Place of Presentation: 新潟
  • Year and Date: 2012-11-10
• [Presentation] Identification of non-small-cell lung cancer with activating EGFR mutations in malignant effusion and cerebrospinal fluid (2012)
  • Author(s): Kawahara Akihiko
  • Organizer: 37^<th> European Congress of Cytology
  • Place of Presentation: Croatia, Dubrovnik
  • Year and Date: 2012-09-30
• [Presentation] Interleukin 1 promotes lymph node metastasis by lung cancer cells through modification of tumor stroma cells (2012)
  • Author(s): Tomohiro Shibata, Kosuke Watari, Akihiko Kawahara, Yuichi Murakami, Hiroshi Nabeshima, Koichi Azuma, Masayoshi Kage, Naofumi Mukaida, Michihiko Kuwano, Takashi Takahashi, Mayumi Ono
  • Organizer: 71th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 71th Annual Meeting of the Japanese Cancer Association
  • Year and Date: 2012-09-21
• [Presentation] A novel mechanism for acquired resistance to EGFR-TKI in human lung cancer : loss of activating mutant EGFR gene allele (2012)
  • Author(s): Rina Kanda, Yuichi Murakami, Akihiko Kawahara, Koichi Azuma, Masayoshi Kage, Tomoko Tahira, Michihiko Kuwano, Mayumi Ono
  • Organizer: 71th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Hokkaido
  • Year and Date: 2012-09-21
• [Presentation] Characteristics of immunohistochemical ALK-positive lung cancer (2012)
  • Author(s): Jun Akiba, Akihiko Kawahara, Masayoshi Kage, Hirohisa Yano
  • Organizer: 71th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Hokkaido
  • Year and Date: 2012-09-19
• [Presentation] ワークショップ.肺癌患者の診断と治療における呼吸器細胞診の役割 (2011)
  • Author(s): 河原明彦,多比良朋希,安部秀幸,山口知彦,吉田友子,秋葉純,鹿毛政義
  • Organizer: 第50回日本臨床細胞学会秋期大会
  • Place of Presentation: 東京
  • Year and Date: 2011-10-23
• [Presentation] Immunocytochemical diagnosis of activating EGFR mutations in NSCLC using mutation-specific antibodies (2011)
  • Author(s): Kawahara Akihiko, Koichi Azuma, Kuwano Michihiko, Masayoshi Kage, Mayumi Ono
  • Organizer: 70^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] 再発肺癌細胞におけるEGFR遺伝子変異の免疫細胞化学による検出 (2011)
  • Author(s): 河原明彦,山口知彦,安倍秀幸,多比良朋希,吉田友子,内藤嘉紀,秋葉純,鹿毛政義
  • Organizer: 第52回日本臨床細胞学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2011-05-21