Elsevier

Lung Cancer

Volume 49, Supplement 1, July 2005, Pages S109-S111
Lung Cancer

Soluble mesothelin-related protein—A blood test for mesothelioma

https://doi.org/10.1016/j.lungcan.2005.03.020Get rights and content

Summary

Identification of tumor marker for mesothelioma (MM) might prove useful in diagnosis as well as for monitoring tumor in response to therapy and for screening at-risk individuals. We tested the hypothesis that soluble mesothelin-related protein (SMRP), a mesothelin family member, in the serum would be such a marker. Our data show that determination of SMRP in serum is a marker of MM with a sensitivity of sensitivity 83% and specificity 95% in the first 48 MM patients tested. Changes in serum SMRP levels parallel clinical course/tumor size and SMRP is elevated in 75% of patients at diagnosis. SMRP should also be useful for monitoring disease progression, and importantly, may prove useful for screening asbestos-exposed individuals for early MM.

Introduction

Mesothelioma (MM) is an aggressive, incurable malignancy of serosal surfaces that presents relatively late in its course [1], [2], [3], [4]. Serum markers are frequently used to help diagnosis of cancer and to follow response to treatment [5], [6], [7], [8], [9] and can facilitate early diagnosis of cancer. There is some evidence that MM patients respond better to therapy if it is delivered early in the disease [10], [11], [12], [13]. Any marker of early mesothelioma should therefore lead to more effective therapy. A few MM markers have been published [13], [14] but none are in routine use. Mesothelin is a 40 kDa cell surface GPI-linked protein signalling [15], [16], [17], [18], [19] present in several forms—in this study, we use the term soluble mesothelin-related protein (SMRP) to refer to the protein detected by the sandwich ELISA [19]. This report summarizes our work evaluating SMRP in μM [20].

Section snippets

Patients and controls

Serum samples were collected consecutively from patients with the following diseases: 48 patients with mesothelioma; control sera from 28 healthy adults with no history of asbestos exposure, 40 healthy, age-matched adults with documented asbestos exposure, 92 patients with lung inflammatory diseases (asbestosis (22), idiopathic pulmonary fibrosis (22), sarcoidosis (32), systemic lupus erythematosis (3), rheumatoid arthritis with lung involvement (4), other interstitial or immune lung diseases

SMRP is elevated in the serum of patients with proven mesothelioma

Sera from 40 of 48 patients with established MM had significantly elevated SMRP levels at all serum dilutions examined, as compared to asbestos-exposed (p < 0.001) and non-asbestos-exposed controls (p < 0.001). Only 10 of the 228 comparison sera were positive and 7 of these were in the asbestos-exposed healthy group.

SMRP levels in the serum of only 2 of 160 patients with inflammatory or malignant pulmonary or pleural diseases other than MM were elevated. Of the seven patients who presented with

Discussion

The majority of patients with MM had elevated serum levels of SMRP, with most showing elevated SMRP in the serum when they had mimimal tumor bulk present, suggesting that SMRP is a sensitive marker of tumor [20]. Inflammatory and malignant lung or pleural disease rarely caused an increase in SMRP levels increasing the potential usefulness of the test.

Elevated serum SMRP levels in this cohort of patients has a sensitivity of 83% and a specificity of 100% for MM diagnosis [20]. Measurement of

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