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Journal of Thoracic Oncology
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Original Article|Articles in Press

Micropapillary and Solid Histologic Patterns in N1 and N2 Lymph Node Metastases Are Independent Factors of Poor Prognosis in Patients with Stage II-III Lung Adenocarcinoma

Published:January 18, 2023DOI:https://doi.org/10.1016/j.jtho.2023.01.002
Micropapillary and Solid Histologic Patterns in N1 and N2 Lymph Node Metastases Are Independent Factors of Poor Prognosis in Patients with Stage II-III Lung Adenocarcinoma
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      ABSTRACT

      Introduction

      High-grade histologic patterns are associated with poor prognosis in patients with primary nonmucinous lung adenocarcinoma (ADC). We investigated whether the presence of micropapillary and/or solid patterns (MIP/SOL) in lymph node (LN) metastases has prognostic value.

      Methods

      Patients who underwent lobectomy for pathologic stage II-III lung ADC with N1 or N2 LN metastases (n=360; 2000–2012) were analyzed. We assessed overall survival (OS), lung cancer–specific cumulative incidence of death (LC-CID), and cumulative incidence of recurrence (CIR) between patients with and without MIP/SOL patterns in LN metastases. Multivariable Cox regression analysis was used to quantify the association between MIP/SOL patterns and outcomes.

      Results

      Micropapillary and solid patterns in LN metastases were associated with a higher incidence of smoking history (p=0.004), tumor necrosis (p=0.013), and spread of tumor through air spaces (p<0.0001), a higher prevalence of micropapillary or solid pattern in the primary tumor (p<0.0001), shorter OS (5-year OS, 40% [95% CI, 29%-56%] vs. 63% [48-83%) for no MIP/SOL in LNs; p=0.03), higher LC-CID (5-year, 43% [29%-56%] vs. 14% (4-29%); p=0.013), and higher CIR (5-year, 65% [50%-77%] vs. 43% (25-60%); p=0.057). Micropapillary and solid patterns in LN metastases were independently associated with poor outcomes: OS (hazard ratio [HR], 1.81 [95% CI, 1.00-3.29]; p=0.05), LC-CID (HR, 3.10 [1.30-7.37]; p=0.01), and CIR (HR, 2.06 [1.09-3.90]; p=0.026).

      Conclusion

      MIP/SOL histological patterns in N1 or N2 LN metastases are associated with worse outcomes in patients with stage II-III lung ADC. MIP/SOL histological patterns in LN metastases can stratify patients with high-risk stage II-III lung ADC.

      Keywords

      Abbreviations:

      ACI (acinar), ADC (adenocarcinoma), CI (confidence interval), CIR (cumulative incidence of recurrence), HR (hazard ratio), IQR (Interquartile range), LC-CID (lung cancer–specific cumulative incidence of death), LEP (lepidic), LN (lymph node), MIP (micropapillary), N (nodal), OS (overall survival), PAP (papillary), SOL (solid), STAS (spread of tumor through air spaces), T (tumor)
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      Article info

      Publication history

      Accepted: January 3, 2023
      Received in revised form: December 15, 2022
      Received: October 3, 2022

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      Research Support: P.S.A.’s laboratory work is supported by grants from the National Institutes of Health (P30 CA008748, R01 CA236615-01, and R01 CA235667), the U.S. Department of Defense (BC132124, LC160212, CA170630, CA180889, and CA200437), the Batishwa Fellowship, the Comedy vs. Cancer Award, the Dalle Pezze Foundation, the Derfner Foundation, the Esophageal Cancer Education Fund, the Geoffrey Beene Foundation, the Memorial Sloan Kettering Technology Development Fund, the Miner Fund for Mesothelioma Research, the Mr. William H. Goodwin and Alice Goodwin, the Commonwealth Foundation for Cancer Research, and the Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center. P.S.A.’s laboratory receives research support from ATARA Biotherapeutics. All sponsors played no role in any aspect of this work. D.R. J’s laboratory work is supported by National Institutes of Health grants R01CA217169 and R01CA240472.

      Conflict of Interest Statement: D.R.J. is a member of the Advisory Council for Astra Zeneca and a member of a Clinical Trial Steering Committee for Merck. P.S.A. declares research funding from ATARA Biotherapeutics; Scientific Advisory Board Member and Consultant for ATARA Biotherapeutics, Bayer, Carisma Therapeutics, Imugene, ImmPactBio, Johnson & Johnson, Orion Pharma, Outpace Bio; Patents, royalties, and intellectual property on mesothelin-targeted CAR and other T-cell therapies, which have been licensed to ATARA Biotherapeutics, issued patent method for detection of cancer cells using virus, and pending patent applications on PD-1 dominant negative receptor, on a wireless pulse-oximetry device, and on an ex vivo malignant pleural effusion culture system.

      Memorial Sloan Kettering Cancer Center has licensed intellectual property related to mesothelin-targeted CARs and T-cell therapies to ATARA Biotherapeutics and has associated financial interests.

      CRediT roles:

      Yan Li: Investigation, data curation, roles/writing – original draft

      Alexander J. Byun: Data curation & validation

      Jennie K. Choe: Data curation, investigation

      Shaohua Lu: Investigation, methodology

      David Restle: Validation, writing - review & editing

      Takashi Eguchi: Data curation, methodology, investigation, writing - review & editing

      Kay See Tan: Formal analysis, visualization

      Jasmeen Saini: Investigation, writing - review & editing

      James Huang: Writing - review & editing

      Gaetano Rocco: Writing - review & editing

      David R. Jones: Writing - review & editing

      William D. Travis: Data curation, investigation & writing - review & editing

      Prasad S. Adusumilli: Conceptualization, Funding acquisition, Project administration, Supervision, writing - review & editing.

      Identification

      DOI: https://doi.org/10.1016/j.jtho.2023.01.002

      Copyright

      © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

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