Peripheral location, TTF-1 expression and prognosis of SCLC

• Project/Area Number: 24501347
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnosis
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: NISHIO Makoto 公益財団法人がん研究会, その他部局等, その他 (00281593)
• Co-Investigator(Kenkyū-buntansha): ISHIKAWA Yuichi 公益財団法人がん研究会がん研究所, 病理部, 部長 (80222975)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 小細胞肺がん / TTF-1 / マイクロアレイ / 予後 / 免疫組織化学

Outline of Final Research Achievements

In this study, we examined whether SCLC is really a central-type tumor and the relationship between tumor location, TTF-1 expression and prognosis of SCLC.　Ninety six SCLCs, diagnosed from biopsies or surgical materials, for which detailed computed tomography (CT) images were available, were collected consecutively from Japanese patients between 2004 and 2011. We examined the location of the primary tumor (central or peripheral) using thin-sliced CT, a TTF-1 immunohistochemical expression, and clinicopathology including prognosis.Of the 96 SCLCs, 75% were of the peripheral type and found to have a significantly worse prognosis than central-type tumors. TTF-1 expression was significantly correlated with peripheral location (p = 0.030). Multivariate analysis revealed that high TNM stages and the peripheral location were independent markers for poor survival. TTF-1 is a marker for peripheral location and a poor prognosis for SCLC.

Research Products

• [Journal Article] The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. (2014)
  • Author(s): Friboulet, L., Li, N., Katayama, R., Lee, C. C., Gainor, J. F., Crystal, A. S., Michellys, P. Y., Awad, M. M., Yanagitani, N., Kim, S., Pferdekamper, A. C., Li, J., Kasibhatla, S., Sun, F., Sun, X., Hua, S., McNamara, P., Mahmood, S., Lockerman, E. L., Fujita, N., Nishio, M., Harris, J. L., Shaw, A. T., Engelman, J. A.
  • Journal Title: Cancer Discov. Volume: 4 (6) Pages: 662-673
  • Peer Reviewed
• [Journal Article] A subset of small cell lung cancer with low neuroendocrine expression and good prognosis: a comparison study of surgical and inoperable cases with biopsy. (2014)
  • Author(s): Hamanaka, W., Motoi, N., Ishikawa, S., Ushijima, M., Inamura, K., Hatano, S., Uehara, H., Okumura, S., Nakagawa, K., Nishio, M., Horai, T., Aburatani, H., Matsuura, M., Iwasaki, A., Ishikawa, Y.
  • Journal Title: Hum. Pathol. Volume: 45 (5) Pages: 1045-1056
  • Peer Reviewed
• [Journal Article] Phase II study of erlotinib for acquired resistance to gefitinib in patients with advanced non-small cell lung cancer. (2014)
  • Author(s): Horiike, A., Yamamoto, N., Tanaka, H., Yanagitani, N., Kudo, K., Ohyanagi, F., Ono, A., Naito, T., Murakami, H., Horai, T., Nishio, M.
  • Journal Title: Anticancer Res. Volume: 34 (4) Pages: 1975-1981
  • Peer Reviewed
• [Journal Article] Dacomitinib as first-line treatment in patients with clinically or molecularly selected advanced non-small-cell lung cancer: a multicentre, open-label, phase 2 trial. (2014)
  • Author(s): Janne, P. A., Ou, S. H., Kim, D. W., Oxnard, G. R., Martins, R., Kris, M. G., Dunphy, F., Nishio, M., O'Connell, J., Paweletz, C., Taylor, I., Zhang, H., Goldberg, Z., Mok, T.
  • Journal Title: Lancet Oncol. Volume: 15 (13) Pages: 1433-1441
  • Peer Reviewed
• [Journal Article] Etoposide and cisplatin versus irinotecan and cisplatin in patients with limited-stage small-cell lung cancer treated with etoposide and cisplatin plus concurrent accelerated hyperfractionated thoracic radiotherapy (JCOG0202): a randomised phase 3 study. (2014)
  • Author(s): Kubota, K., Hida, T., Ishikura, S., Mizusawa, J., Nishio, M., Kawahara, M., Yokoyama, A., Imamura, F., Takeda, K., Negoro, S., Harada, M., Okamoto, H., Yamamoto, N., Shinkai, T., Sakai, H., Matsui, K., Nakagawa, K., Shibata, T., Saijo, N., Tamura, T.
  • Journal Title: Lancet Oncol. Volume: 15 (1) Pages: 106-113
  • Peer Reviewed
• [Presentation] A randomized phase III study of cisplatin (CDDP), etoposide (ETOP) and irinotecan versus topotecan as second-line chemotherapy in patients with sensitive relapsed small-cell lung cancer (SCLC): Japan Clinical Oncology Group study JCOG0605. (2014)
  • Author(s): Goto, K., Ohe, Y., Seto, T., Takahashi, T., Nakagawa, K., Yamamoto, N., Yokoyama, A., Takeda, K., Nishio, M., Mori, K., Satouchi, M., Hida, T., Kudoh, S., Nogami, N., Imamura, F., Kiura, K., Okamoto, H., Sawa, T., Shibata, T., Tamura, T.
  • Organizer: ASCO 50th Annual Meeting
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2014-05-30
• [Presentation] Prophylactic cranial irradiation (PCI) has a detrimental effect on the overall survival (OS) of patients (pts) with extensive disease small cell lung cancer (ED-SCLC): Results of a Japanese randomized phase III trial. (2014)
  • Author(s): Seto, T., Takahashi, T., Yamanaka, T., Harada, H., Nokihara, H., Saka, H., Nishio, M., Nakagawa, K., Takayama, K., Ishimoto, O., Takeda, K., Yoshioka, H., Tachihara, M., Sakai, H., Goto, K., Yamamoto, N.
  • Organizer: ASCO 50th Annual Meeting
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2014-05-30
• [Presentation] 末梢型小細胞肺がんは中枢型に比べ予後不良で、遺伝子発現プロファイルが異なる (2013)
  • Author(s): 宮内栄作、齋藤雄一、二宮浩範、 元井紀子、西尾誠人、奥村栄、 石川雄一
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: ホテルニューオータニ東京
• [Presentation] Primary location of small cell lung cancer (SCLC) and TTF-1 expression: are most SCLCs really of hilar origin? (2012)
  • Author(s): Eisaku Miyauchi, Hiroshi Ono, Hironori Ninomiya, Kentaro Inamura, Noriko Motoi, Makoto Nishio, Sakae Okumura, Yuichi Ishikawa.
  • Organizer: 3rd European Lung Cancer Conference (ELCC)
  • Place of Presentation: Geneva, Switzerland
• [Presentation] 小細胞肺がんの層別化の試み－発生起源の再検討と発がん機構に注目して－ (2012)
  • Author(s): 宮内栄作、齋藤雄一、二宮浩範、元井紀子、西尾誠人、奥村栄、石川雄一
  • Organizer: 第53回日本肺癌学会総会
  • Place of Presentation: 岡山コンベンションセンター