Author of

• 12769

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  P3.18 - Poster Session 3 - Pathology (ID 177)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12775

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    P3.18-006 - Non-terminal respiratory unit lung adenocarcinoma: can have 3 subtypes and is associated with poor prognosis (ID 1727)

    09:30 - 09:30  |  Author(s): S. Sumiyoshi
    • Abstract

    Background
    Terminal respiratory unit (TRU) adenocarcinoma, which is proposed as a distinct subset of lung adenocarcinomas, develops in periphery of the lung parenchyma, is similar in cell morphology to type II pneumocytes or Clara cells, is positive for the expression of thyroid transcription factor-1 (TTF-1), and harbors mutations in the gene encoding the epidermal growth factor receptor (EGFR). The clinicopathological characteristics are generally well defined. In contrast, few studies have focused on non-TRU type adenocarcinomas. We herein analyzed clinicopathologic and prognostic findings of non-TRU type adenocarcinomas.

    Methods
    We selected 244 consecutive patients with lung adenocarcinomas underwent pulmonary resection at Kyoto University Hospital between January 2001 and December 2007. All cases were classified according to IASLC/ATS/ERS criteria. Findings of significant prognostic factors for lung adenocarcinomas prompted analyses of lymphatic invasion, vascular invasion, pleural invasion, tumor grade. We annalyzed immunohistochemical expression of the mucins MUC5B, MUC5AC, as well as TTF-1 using TMA blocks comprising lung adenocarcinoma specimens from the 244 patients. The presence of mutations in EGFR and KRAS was also determined.

    Results
    TTF-1, MUC5B, and MUC5AC were detected in 219 (89.6%), 75 (30.7%) and 33 cases (13.5%), respectively. Cluster analysis of the protein expression and EGFR and KRAS mutations yielded four classes of tumors as follows: TRU-type (TTF-1(+), MUC5B(-), MUC5AC(-)); Combined-type (TTF-1(+), MUC5B(+) and/or MUC5AC(+)); Bronchiolar-type (TTF-1(-), MUC5B(+) and/or MUC5AC(+)); and Null-type (TTF-1(-), MUC5B(-), MUC5AC(-), EGFR mutations(-), KRAS mutations(-)). TRU-type tumors were significantly associated with non-mucinous adenocarcinoma in situ (AIS), whereas Bronchiolar-type tumors were associated with mucinous AIS. Combined-type cases were intermediate in morphology between TRU-type and Bronchiolar-type cases (P < 0.001). TRU-type was associated with significantly better prognosis (5-year disease free survival rate (5y-DFS-rate) = 75.2%, 5-year overall survival rate (5y-OS-rate) = 83.8%), followed by Combined-type (5y-DFS-rate = 61.7%, 5y-OS-rate = 73.2%), Bronchiolar-type (5 y-DFS-rate = 53.6%, 5y-OS-rate = 53.9%), and Null-type (5y-DFS-rate = 40.0%, 5 y-OS-rate = 40.0%). Multivariate analyses indicated that non-TRU type significantly correlated with poorer prognosis for DFS (hazard ratio (HR) = 1.946; 95% confidence interval (CI) 1.139-3.322; P = 0.015) and OS (HR = 1.933; 95% CI 1.072-3.491; P = 0.030).

    Conclusion
    The present study demonstrates that lung adenocarcinomas expressing MUC5B and MUC5AC could represent the non-TRU type and have a poorer prognosis than that of TRU-type lung adenocarcinomas. In addition, three distinct subtypes of non-TRU type adenocarcinomas were discovered. There are no effective treatments for patients with non-TRU type lung adenocarcinoma, while patients with TRU-type lung adenocarcinoma can be treated with EGFR inhibitors. Therefore, the characterization of non-TRU type lung adenocarcinomas described here, suggests that patients with this disease can be identified as candidates for receiving treatments that will hopefully be developed in the future.