Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 May;18(5):608-619.
doi: 10.1016/j.jtho.2023.01.002. Epub 2023 Jan 18.

Micropapillary and Solid Histologic Patterns in N1 and N2 Lymph Node Metastases Are Independent Factors of Poor Prognosis in Patients With Stages II to III Lung Adenocarcinoma

Yan Li  1 , Alexander J Byun  2 , Jennie K Choe  2 , Shaohua Lu  3 , David Restle  2 , Takashi Eguchi  4 , Kay See Tan  5 , Jasmeen Saini  2 , James Huang  2 , Gaetano Rocco  2 , David R Jones  2 , William D Travis  6 , Prasad S Adusumilli  7
Affiliations

Micropapillary and Solid Histologic Patterns in N1 and N2 Lymph Node Metastases Are Independent Factors of Poor Prognosis in Patients With Stages II to III Lung Adenocarcinoma

Yan Li et al. J Thorac Oncol. 2023 May.

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 (MIP), solid (SOL), or both patterns in lymph node (LN) metastases has prognostic value.

Methods: Patients who underwent lobectomy for pathologic stages II to 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: MIP and SOL 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 MIP or SOL in the primary tumor (p < 0.0001), shorter OS (5-y OS, 40% [95% confidence interval or CI: 29%-56%] versus 63% [48%-83%] for no MIP/SOL in LNs, p = 0.03), higher LC-CID (5-y, 43% [29%-56%] versus 14% [4%-29%], p = 0.013), and higher CIR (5-y, 65% [50%-77%] versus 43% [25%-60%], p = 0.057). MIP and SOL 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).

Conclusions: MIP/SOL histologic patterns in N1 or N2 LN metastases are associated with worse outcomes in patients with stages II to III lung ADC. MIP/SOL histologic patterns in LN metastases can stratify patients with high-risk stages II to III lung ADC.

Keywords: Micropapillary adenocarcinoma; N classification; Nodal metastasis; Non–small cell lung cancer; Solid adenocarcinoma.

PubMed Disclaimer

Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.
Patient flowchart. ADC, adenocarcinoma; IMA, invasive mucinous adenocarcinoma; LN, lymph node.
Figure 2.
Figure 2.
Prevalence of micropapillary (MIP) and solid (SOL) pattern in lymph nodes (LNs) and primary tumors. (A) Violin plot describing the distribution of MIP and SOL pattern in LN from patients with N1 versus N2 staging. (B) Violin plot describing the distribution of MIP and SOL pattern in LN from patients with single versus multiple involved LNs. (C) Violin plot describing the distribution of MIP and SOL pattern in primary tumors of which corresponding LNs had MIP and/or SOL pattern present. (D) Violin plot describing the distribution of MIP and SOL pattern in primary tumors of which corresponding LNs were either acinar (ACI), papillary (PAP), MIP, or SOL predominant. (E) Alluvial plot describing the proportion of patients with each predominant histologic subtype in the primary tumor and in the corresponding LNs. (F) Correlation of the percentage of histologic patterns between primary tumors and LNs. For each histological subtype (ACI, PAP, MIP and SOL), the mean percentage of the pattern in the LN across patients is calculated within four groups of increasing percentages (0–4%, 5–24%, 25–49%, 50–100%) of the pattern in the primary tumor. #, p>0.05; *p<0.05; ***p<0.0001.
Figure 3.
Figure 3.
Overall survival, lung cancer–specific cumulative incidence of death, and cumulative incidence of recurrence for patients stratified by N1 versus N2 staging (A-C) or micropapillary (MIP) and/or solid (SOL) patterns in lymph nodes (LNs) (D-F).
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Asamura H, Chansky K, Crowley J, et al. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revision of the N Descriptors in the Forthcoming 8th Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2015;10:1675–1684. 10.1097/jto.0000000000000678. - DOI - PubMed
    1. Li S, Yan S, Lu F, et al. Validation of the 8th Edition Nodal Staging and Proposal of New Nodal Categories for Future Editions of the TNM Classification of Non-Small Cell Lung Cancer. Ann Surg Oncol 2021;28:4510–4516. 10.1245/s10434-020-09461-y. - DOI - PubMed
    1. Yun JK, Lee GD, Choi S, et al. Comparison between lymph node station- and zone-based classification for the future revision of node descriptors proposed by the International Association for the Study of Lung Cancer in surgically resected patients with non-small-cell lung cancer. Eur J Cardiothorac Surg 2019;56:849–857. 10.1093/ejcts/ezz147. - DOI - PubMed
    1. Park BJ, Kim TH, Shin S, et al. Recommended Change in the N Descriptor Proposed by the International Association for the Study of Lung Cancer: A Validation Study. J Thorac Oncol 2019;14:1962–1969. 10.1016/j.jtho.2019.07.034. - DOI - PubMed
    1. Chiappetta M, Lococo F, Leuzzi G, et al. External validation of the N descriptor in the proposed tumour-node-metastasis subclassification for lung cancer: the crucial role of histological type, number of resected nodes and adjuvant therapy. Eur J Cardiothorac Surg 2020;58:1236–1244. 10.1093/ejcts/ezaa215. - DOI - PubMed

Publication types