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Thoracic

E169: Evaluating the Prognostic Impact of Tumor Microenvironment of Metastasis Doorways in Non-Small Cell Lung Cancer and Invasive Pancreatic Ductal Adenocarcinoma

    ePoster Abstract Author(s)

  • Rajika Jindani, MD MPH MS

    Thoracic Oncology Research Fellow/ General Surgery Resident
    Montefiore Medical Center/Albert Einstein College of Medicine, United States

    • Submitter(s)

  • Rajika Jindani, MD MPH MS

    Thoracic Oncology Research Fellow/ General Surgery Resident
    Montefiore Medical Center/Albert Einstein College of Medicine, United States

    • Author(s)

  • Rajika Jindani, MD MPH MS

    Thoracic Oncology Research Fellow/ General Surgery Resident
    Montefiore Medical Center/Albert Einstein College of Medicine, United States

  • LA

    Lina Ariyan, BS

    PhD Student
    Albert Einstein College of Medicine, United States

  • MM

    Maria Maldifassi, PhD

    Assistant Research Professor
    Albert Einstein College of Medicine, United States

  • EZ

    Erika Pereira Zambalde, PhD

    Research Fellow
    Albert Einstein College of Medicine, United States

  • FM

    Francisco Puerta Martinez, PhD

    Research Assistant Professor
    Albert Einstein College of Medicine, United States

  • Jorge Humberto Rodriguez-Quintero, MD

    Thoracic Oncology Research Fellow/ General Surgery Resident
    Montefiore Medical Center/ Albert Einstein College of Medicine
    Bronx, New York, United States

  • MW

    Meng Wang, MD PhD

    Research Fellow
    Albert Einstein College of Medicine, United States

  • JY

    Jihua Yang, MD MS

    Research Fellow
    Albert Einstein College of Medicine, United States

  • HC

    Haiying Cheng, MD

    Professor
    Department of Oncology, Albert Einstein School of Medicine, United States

  • RE

    Robert Eddy, PhD

    Research Professor
    Albert Einstein College of Medicine, United States

  • NP

    Nicole Panarelli, MD

    Surgical Pathologist
    Department of Surgery and Pathology, Albert Einstein School of Medicine, United States

  • MO

    Maja Oktay, MD PhD

    Professor of Surgery and Pathology
    Albert Einstein College of Medicine, United States

  • JC

    John Condeelis, PhD

    Chair Emeritus Department of Anatomy & Structural Biology
    Albert Einstein College of Medicine, United States

  • BS

    Brendon Stiles, MD

    Professor, Department of Cardiothoracic & Vascular Surgery
    Montefiore Medical Center/ Albert Einstein College of Medicine
    Bronx, New York, United States

  • JM

    John C. McAuliffe, MD PhD

    Associate Professor, Department of Surgery and Pathology
    Montefiore Medical Center/ Albert Einstein College of Medicine
    Bronx, New York, United States

Introduction: Non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) are leading causes of cancer-related deaths attributed largely to overwhelming metastatic burden. The Tumor Microenvironment of Metastasis (TMEM) doorway is the sole portal of tumor cell intravasation in breast cancer and its density within a tumor is a prognostic tool for distant metastatic treatment failure. The aim of this study is to evaluate whether TMEM doorway score correlates with clinical features, such as tumor grade, treatment status, and local and distant metastasis in NSCLC and PDAC. These findings would support the hypothesis of a common mechanism of dissemination in adenocarcinomas.

Methods: This project is a collaborative effort to investigate the role of TMEM doorways as a common, actionable mechanism of dissemination in adenocarcinoma. Patients with NSCLC and PDAC who underwent surgical resection from 2013-2022 were identified through retrospective chart review and human tissue slides were obtained from institutional tissue banks. Kaplan-Meier curves and multivariable Cox regression will be used to assess differences in demographics and cancer-specific outcomes based on TMEM doorway score.

Results:

The mean TMEM doorway score was 51/hpf for NSCLC and 9/hpf for PDAC. In the NSCLC group, metastases were found in the brain (54.5%), liver (9%), ribs (18.2%), and lung (18.2%). In the PDAC group, most metastases were found in the liver (47.1%) and lungs (41.2%). In the PDAC cohort, high TMEM doorway scores were found in high grade (Grade 2, 72.7% vs. Grade 1, 30.4%, p=.008) and poorly differentiated tumors (50% vs. moderate-well, 25.8%, p=0.36). In NSCLC patients, TMEM doorway score was not associated with pathologic features or recurrence in this small cohort.  Progression-free survival data is being followed but remains immature (Figure 2).

Conclusions: The identification of the TMEM doorway in NSCLC and PDAC is a novel finding, potentially linked to metastatic processes. These results support the rationale for expanded evaluation of the implications of the TMEM doorway in oncologic outcomes in NSCLC and PDAC. Functionality of TMEM doorways should be assessed to determine their prognostic value. 

 

Learning Objectives:

  • Upon completion, the participant will be able to define what a Tumor Microenvironment of Metastasis (TMEM) doorway is structurally and functionally, and its correlation with Mena gene expression.
  • Upon completion, the participant will be able to understand the utility of the TMEM doorway score as a prognostic marker in NSCLC and PDAC.
  • Upon completion, the participant will be able to list the clinical features associated with higher TMEM doorway score.