Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin

Abstract

BackgroundWe evaluated possible diagnostic and prognostic values of serum midkine in malignant pleural mesothelioma in comparison with those of serum mesothelin, a well-established diagnostic biomarker.MethodsSerum mesothelin and midkine levels were determined with an enzyme-linked immunosorbent assay. We examined specimens from 95 Turkish cases with malignant pleural mesothelioma, 56 metastatic cancers to pleura, 27 other types of benign pleural diseases and 20 benign asbestos pleurisy. The cut-off values were 1.5 nmol/L for mesothelin and 421 pg/mL for midkine.ResultsSensitivity and specificity of mesothelin were 51.6 and 71.4%, 51.6 and 85.2%, and 51.6 and 85% for differentiating mesothelioma from metastatic cancers to pleura, other benign pleural diseases and benign asbestos pleurisy, respectively. Sensitivity and specificity of midkine were 61.1 and 41.1%, 61.1 and 48.1%, and 61.1 and 75% to distinguish mesothelioma from metastatic cancers to pleura, other benign pleural diseases and benign asbestos pleurisy, respectively. Combination of both biomarkers did not improve the differential diagnostic efficacy. Mesothelin levels were elevated in the epitheloid type and in the advanced cases, but were not related to the prognosis. In contrast, elevated baseline levels of midkine were independently associated with a poor prognosis of mesothelioma patients after adjusting for the stage, the histological subtypes and treatment schedules (HR = 1.84; 95% CI: 1.09-3.09) (p = 0.022).ConclusionsSerum mesothelin showed moderate sensitivity and high specificity to differentiate malignant pleural mesothelioma from metastatic malignancy to pleura and from benign pleural diseases. In contrast, midkine was a useful marker for predicting prognosis of mesothelioma patients.

Diagnostic impact of high serum midkine level in patients with gastric cancer

“…Similar to previous reports on mesothelioma and head and neck carcinoma, there was no clear association between tumor progression and s‐MK positive rate. Although the number of stage III/IV patients in our present study was not sufficient, we could not find significantly higher positive rates in stage III/IV patients than in stage I/II patients.…”

“…Although the number of stage III/IV patients in our present study was not sufficient, we could not find significantly higher positive rates in stage III/IV patients than in stage I/II patients. Such a tendency was also observed in previous reports, which may be explained by the hypothesis that the biological characteristic of cancer cells to express MK at the early phase of carcinogenesis remained unchanged during tumor progression. Unfortunately, the reason behind the s‐MK positive rate being relatively low, and lower than the CEA positive rate in stage III, was unclear.…”

“…Mean value obtained from 99 healthy volunteers was 208 pg/mL, with a standard deviation (SD) of 107 pg/mL, according to the manufacturer's protocol data. Therefore, the cut‐off value was fixed as mean + 2 SD to be 421 pg/mL as previously described …”

“…Recently, an ELISA using monoclonal antibodies against midkine was developed . We evaluated the diagnostic abilities of this assay system using monoclonal antibodies for malignant mesothelioma and head and neck cancer . Only two reports used polyclonal antibody ELISA to evaluate s‐MK levels in patients with gastric cancer .…”

Biomarkers for Early Diagnosis and Prognosis of Malignant Pleural Mesothelioma: The Quest Goes on

“…The accuracy of MM diagnosis has been improved using a series of immune-histochemical markers (IHC), including mesothelial markers (calretinin, the most sensitive and WT-1, the most specific) and carcinoma-related markers (CEA, CD15, Ber-EP4, MOC-31, TTF-1) for differential diagnosis. Combining the results obtained with these markers together, it is possible to obtain a more reliable diagnosis [ 36 , 37 , 38 , 39 , 40 ]. In the light of secondary prevention, our attention has been focused on the research of non-invasive biological indicators that allow an early diagnosis of MM and that can be applied to subgroups of high-risk populations, such as former subjects exposed to asbestos.…”