A Prospective Clinical Trial to Evaluate Mesothelin as a Biomarker for the Clinical Management of Esophageal Adenocarcinoma (EAC) Patients The incidence of esophageal adenocarcinoma (EAC) is rising at an annual rate of 8%. Most EAC patients present at an advanced stage disease with an overall 5-year survival rate of 10%. Of the patients who present with potentially curable disease, majority will already have local-regional advanced disease. Although combined modality treatment, the current standard of care for locally advanced disease, improves survival, lack of accurate clinical evaluation of tumor burden and treatment response is a significant limitation in selecting appropriate treatment in a timely fashion. In spite of the radiographic and endoscopic imaging, one in four patients with a presumed early-stage disease are found to have more extensive disease (T3 or N1) at the time of surgery. These patients would have benefited from multimodality therapy. In patients treated with neo- adjuvant therapy for local-regional advanced disease, assessment of therapy response remains inaccurate. Identification and validation of a biomarker that reflects tumor burden, therapy response, and recurrence will be highly valuable for the clinical management and clinical trials of EAC patients. In this research proposal, based on our promising retrospective data, we aim to investigate serum and tissue mesothelin as a biomarker to improve the clinical management of EAC patients. Mesothelin is a cell surface tumor-differentiation antigen, the N-terminal of which is cleaved and secreted into blood, measured as serum soluble mesothelin-related peptide (SMRP). Increased SMRP levels are demonstrated in mesothelioma, pancreatic and ovarian cancer patients. Recent publications have demonstrated that the level of SMRP correlates with tumor load, therapy response, and prognosis in mesothelioma patients. We propose:
Specific Aim 1 : To prospectively evaluate whether serum SMRP levels correlate with (a) clinical staging, (b) response to neo-adjuvant therapy, and (c) disease recurrence in surgically resected EAC patients.
Specific Aim 2 : To prospectively investigate whether tissue mesothelin expression (a) pre chemo-radiation therapy is a predictor of poor therapy response, and (b) post-resection is a predictor of poor survival. The novelty and impact of this carefully designed prospective proposal extends beyond biomarker study in testing the utility of mesothelin as a marker of Barrett's transformation to EAC;it is immediately translational to benefit 15,000 patients with EAC.

Public Health Relevance

A simple predictive instrument to identify early-stage esophageal adenocarcinoma patients at higher risk for poor therapy response and recurrence;therefore the most likely candidates for selection of therapeutic modality or aggressive surveillance will benefit. In this research proposal, based on our promising retrospective data, we aim to investigate serum and tissue mesothelin as a biomarker to improve the clinical management of esophageal adenocarcinoma patients.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Clinical Oncology Study Section (CONC)
Program Officer
Thurin, Magdalena
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Sloan-Kettering Institute for Cancer Research
New York
United States
Zip Code
Yeh, Yi-Chen; Nitadori, Jun-ichi; Kadota, Kyuichi et al. (2015) Using frozen section to identify histological patterns in stage I lung adenocarcinoma of ? 3 cm: accuracy and interobserver agreement. Histopathology 66:922-38
de Biasi, Andreas R; Villena-Vargas, Jonathan; Adusumilli, Prasad S (2014) Cisplatin-induced antitumor immunomodulation: a review of preclinical and clinical evidence. Clin Cancer Res 20:5384-91
Kadota, Kyuichi; Yeh, Yi-Chen; D'Angelo, Sandra P et al. (2014) Associations between mutations and histologic patterns of mucin in lung adenocarcinoma: invasive mucinous pattern and extracellular mucin are associated with KRAS mutation. Am J Surg Pathol 38:1118-27
Kadota, Kyuichi; Nitadori, Jun-Ichi; Woo, Kaitlin M et al. (2014) Comprehensive pathological analyses in lung squamous cell carcinoma: single cell invasion, nuclear diameter, and tumor budding are independent prognostic factors for worse outcomes. J Thorac Oncol 9:1126-39
Adusumilli, Prasad S (2014) Translational immunotherapeutics: chemoimmunotherapy for malignant pleural mesothelioma. Cancer 120:3268-71
Kadota, Kyuichi; Villena-Vargas, Jonathan; Yoshizawa, Akihiko et al. (2014) Prognostic significance of adenocarcinoma in situ, minimally invasive adenocarcinoma, and nonmucinous lepidic predominant invasive adenocarcinoma of the lung in patients with stage I disease. Am J Surg Pathol 38:448-60
Kadota, Kyuichi; Yeh, Yi-Chen; Sima, Camelia S et al. (2014) The cribriform pattern identifies a subset of acinar predominant tumors with poor prognosis in patients with stage I lung adenocarcinoma: a conceptual proposal to classify cribriform predominant tumors as a distinct histologic subtype. Mod Pathol 27:690-700
Eguchi, Takashi; Kadota, Kyuichi; Park, Bernard J et al. (2014) The new IASLC-ATS-ERS lung adenocarcinoma classification: what the surgeon should know. Semin Thorac Cardiovasc Surg 26:210-22
Adusumilli, Prasad S; Cherkassky, Leonid; Villena-Vargas, Jonathan et al. (2014) Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci Transl Med 6:261ra151
Lee, Ming-Ching; Buitrago, Daniel H; Kadota, Kyuichi et al. (2014) Recent advances and clinical implications of the micropapillary histological subtype in lung adenocarcinomas. Lung Cancer Manag 3:245-253

Showing the most recent 10 out of 14 publications