Detection of Soluble Mesothelin-Related Peptides as Diagnostic Markers of Malignant Pleural Mesothelioma Effusions: Comparison with Cytology
Franco Fedeli, Pieraldo Canessa, Paola Ferro, Enrico Battolla, Paolo Dessanti, Carmen Manta, Cristiana Franceschini, Vincenzo Fontana, Bartolomeo Bacigalupo, Silvia Colli, Mariapia Pistillo, Silvio Roncella. ASL5, La Spezia, Italy; ASL5, Sarzana (SP), Italy; IRCCS A.O.U. San Martino-IST, Genova, Italy
Background: It has been reported that cytology (Cyt) allows the diagnosis of about 30% of malignant mesothelioma pleural effusions (MMPE). Recently, detection of soluble mesothelin (SM) levels has been proposed in order to help diagnosis of MMPE. In this study we assessed the diagnostic performance parameters (DPPs) of SM PE levels from a large cohort of patients and investigated whether SM level can improve Cyt diagnostic accuracy in routine clinical practice of malignant MMPE.
Design: We evaluated SM in 52 MMPE, 129 benign PE (BPE) and 94 non-MM pleural metastasis PE (MtsPE) by means of MesoMark ELISA kit (Fujirebio Diagnostic, Malvern, PA). DDPs were estimated through the ROC analysis. Youden's index was applied to obtain the best cut off level. The degree of correlation of SM in MMPE vs BPE and vs MtsPE was estimated by Diagnostic Odds Ratio (DOR) and by P-value (P) with Chi-square test. All specimens were subjected to routine cytology (Papanicolau staining).
Results: The median SM levels was significantly higher in MMPE (28.2 nM) than in BPE (3.2 nM) or MtsPE (3.8 nM). MMPE vs BPE yielded an AUC of 84.5 (P<0.001) whereas MMPE vs MtsPE yelded an AUC of 79.6 (P<0.001). The cut off level in MMPE was estimated in 9.30 nM at which value we established Se=75%, Sp=93% for MMPE vs BPE and SP=81% for MMPE vs MtsPE. We found SM positive cases (≥ cut off) in 38/52 (73%) MMPE, in 9/129 (7%) BPE (DOR=40, P<0.001) and in 18/94 (19%) MtsPE (DOR=13, P< 0.001).
Cyt was negative in 29/52 (56%) of MMPE (16 epithelioid, 8 sarcomatoid, 2 biphasic, 2 desmoplastic, 1 papillary), among which SM was positive in 20/29 (69%) cases (14 epithelioid, 3 sarcomatoid, 2 biphasic, 1 papillary).
Cyt was positive in 15/52 (29%) of MMPE, (12 epithelioid, 1 sarcomatoid, 2 biphasic), among which SM was negative in 4/15 (27%) cases (all epithelioid).
Finally, in 8/52 (15%) MMPE (7 epithelioid, one papillary) Cyt diagnosis was suspicious and SM was found positive in 7/8 (88%) cases (6 epithelioid, 1 papillary).
Conclusions: SM detection in MMPE may provide additional diagnostic value to Cyt. Combination of SM and Cyt have major diagnostic possibilities if both tests may be performed together.
SM test may be incorporated into clinical practice of MMPE from patients suspicious for malignant mesothelioma.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 68, Tuesday Morning