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Purpose: To explore the potential and diagnostic performance of soluble mesothelin-related peptide (SMRP) as a tumor marker for epithelial ovarian cancer (EOC). Methods: Sera were obtained from 78 EOC patients, 84 benign ovarian tumor patients, 58 healthy volunteers, and 22/78 EOC patients 1 week after surgery. SMRP levels and diagnostic performance were assessed by ELISA using the MESOMARK kit. The combination of SMRP and CA125 in the diagnosis of EOC was assessed. Results: SMRP concentrations were higher in EOC patients than in benign tumor patients and healthy volunteers, and SMRP levels were shown to decrease in EOC patients after surgery. Histological EOC subtypes showed significant differences in SMRP levels. Stage III-IV patients had a higher level of SMRP than stage I-II patients ( P < 0.001). Elevated SMRP levels were also found in higher grade tumors ( P < 0.001). The receiver operating characteristic curve for SMRP was 0.891. The best statistical cut-off for SMRP was 1.3109 nM, with 0.821 sensitivity and 0.979 specificity. When compared with CA125, SMRP performed better in specificity, omission diagnostic rate, positive predictive value, and correction rate, but worse for sensitivity and negative predictive value. The combination of SMRP and CA125 gave a sensitivity of 98.4 % and a specificity of 88.9 %. Conclusion: Serum SMRP is a promising marker for the diagnosis and monitoring of EOC, especially in combination with CA125. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Malignant mesothelioma (MM) carries a poor prognosis and remains a major public health issue in many countries. Outcomes may be improved with earlier detection and this justifies screening the at-risk asbestos-exposed population. Soluble mesothelin is a potential biomarker for MM, but it has been observed to be elevated in patients with reduced kidney function. Defining the relationship between mesothelin concentrations and kidney function will allow more accurate interpretation of this assay. Materials and methods: A cross-sectional study consisting of 144 patients with chronic kidney disease (CKD) was conducted at Sir Charles Gairdner Hospital and Royal Perth Hospital in Western Australia. Only patients with CKD stages II–V were recruited while those with a history of renal transplant, dialysis, or malignancy were excluded. Serum and urine mesothelin and creatinine concentrations were determined. Results: There were 33, 49, 31 and 31 patients in CKD stages II, III, IV and V, respectively recruited. Serum mesothelin increased significantly with increasing serum creatinine (p <0.0001), and worsening stage of CKD (p <0.0001). A significant correlation between urine mesothelin to creatinine ratio and serum mesothelin concentration was detected (p =0.002). No significant difference was found in urine mesothelin to creatinine ratios across the four CKD stage groups. Conclusion: Serum mesothelin concentration is elevated in individuals with renal impairment. Renal function should therefore be taken into account during interpretation of this assay. [Copyright &y& Elsevier]

The aim of the study is to examine the cancer-predictive values of SMRP (soluble mesothelin-related peptides), CA125, and CYFRA21-1 as potential tumor markers for lung cancer and malignant mesothelioma in a cohort of workers formerly exposed to asbestos. A voluntary surveillance program has been established for German workers with former asbestos exposure. A subgroup of 626 subjects with a mean age of 63 years (range 53-70 years) at baseline was enrolled in an extended health examination program with high-resolution computer tomography (HRCT) of the chest and blood drawing between 1993 and 1997. Serum concentrations of SMRP, CA125, and CYFRA21-1 were measured in archived serum samples in 2005 and 2006. A mortality follow-up was conducted through 2007. So far, 12 cases with lung cancer and 20 cases with malignant mesothelioma have been observed in this cohort. The average time between sample collection and diagnosis was 4.7 years. Analyzed biomarkers showed low sensitivities (5-25%) and positive predictive values (4-30%) for both cancer sites. Marker combinations resulted in sensitivities between 5 and 50% and positive predictive values ranging from 3 to 14%. Even in those cases, where biomarker concentrations were available within 36 months before diagnosis, no trend for increasing biomarker levels was observed. The analyzed tumor markers were characterized by high specificities, but low sensitivities. SMRP, CA125, and CYFRA21-1 alone or in combination were less suitable to serve as predictors for the diagnosis of lung cancer or malignant mesothelioma. However, a prospective study with annual sampling might reveal a better predictive value of these markers. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]