Maria Cristiana Franceschini

Sant´Andrea Hospital, Roma, Latium, Italy

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Publications (15)38.05 Total impact

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    ABSTRACT: Mesothelin (SMRP) is regarded as a biomarker of malignant pleural mesothelioma (MPM). Herein, we analyzed the contribution of SMRP detection in pleural effusion and in serum to the diagnosis of MPM with non-positive cytology. The present study included 52 cases of MPM, 43 of pleural benign lesions and 25 of non-MPM pleural metastases. SMRP was measured by MesoMark ELISA (Cis-Bio International Gif/Yvette; France). In non-positive cytology, effusion-SMRP showed higher diagnostic performance than serum-SMRP. We found 38 out of 52 (73.1%) cases of non-positive cytology MPM, out of which 27 (71.0%) were positive for effusion-SMRP (cut-off=12.70 nM) and 18 (47.4%) for serum-SMRP (cut-off=1.08 nM). When cytology, effusion- and serum-SMRP were used in combination, an overall sensitivity in detection of MPM of 78.9% was achieved. The same sensitivity was obtained by combining cytology with effusion-SMRP alone, whereas the combination of serum-SMRP with cytology led to a sensitivity of 61.5%. Detection of both effusion- and serum-SMRP can contribute to improve the diagnosis of MPM with non-positive cytology. However, the analysis of SMRP in effusion makes it unnecessary to test SMRP in the serum. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    No preview · Article · Dec 2014 · Anticancer research
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    ABSTRACT: Pleural EffusionsSESSION TYPE: Original Investigation SlidePRESENTED ON: Tuesday, October 29, 2013 at 02:45 PM - 04:15 PMPURPOSE: Soluble mesothelin-related peptide (SMRP) is regarded as a new promising biomarker for the diagnosis of mesothelioma (MPM) using pleural effusion (PE). In this study, we assessed the relative risk (RR) of cancer in patients diagnosed with non-malignant pleuritis using PE-SMRP levels.METHODS: During March/2008-December/2012, in the Pneumology Department of the Sarzana Hospital (Italy), 86 out of 226 patients with PE, who underwent thoracoscopy, were diagnosed with a benign pleural disease through histo-pathological biopsies and followed up for at least 18 months in order to detect cancer occurrence. PE-SMRP levels were measured by the "MesoMark" ELISA assay kit (Cis-Bio International Gif/Yvette; France). On the basis of the ROC analysis, a level of 20 nM was used as an optimal threshold for classifying patients. Logistic regression was applied to estimate RR and corresponding 95% confidence limits.RESULTS: After a 18-month follow-up, 9/86 (10.5%) patients with negative thoracoscopy developed a pleural malignancy (7 mesotheliomas and 2 lymphomas), 5/9 (55.5%) (4 MPM and 1 lymphoma) had shown a PE-SMRP positive (> 20 nM) result at the time of the first thoracoscopy. In contrast, among 77/86 (89.5%) patients who did not develop malignancies, only 2/77 (2.6%) resulted PE-SMRP positive (both inflammatory pleuritis). In comparison with PE-SMRP negative patients, positive patients showed a RR = 46.9 (95% CL = 6.7-320.9; P-value < 0.001) for cancer and RR = 33.8 (95% CL = 5.1-223.6; P-value < 0.001) for MPM.CONCLUSIONS: Our findings show that SMRP test may have a prognostic value.CLINICAL IMPLICATIONS: We propose a possible application of SMRP detection in PE to point out a false-negative thoracoscopy in non-specific pleuritis.DISCLOSURE: The following authors have nothing to disclose: Pier Aldo Canessa, Paola Ferro, Maria Cristiana Franceschini, Vanna Balestracci, Massimiliano Sivori, Donatella Fini, Enrico Battolla, Vincenzo Fontana, Franco Fedeli, Maria Pia Pistillo, Silvio RoncellaNo Product/Research Disclosure Information.
    No preview · Article · Oct 2013 · Chest
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    ABSTRACT: The aim of this study based on the third phase of the architecture of diagnostic research was to assess the sensitivity and specificity of soluble mesothelin-related peptide (SMRP) in pleural exudative effusions (PE) compared to the histology obtained by medical thoracoscopy as the diagnostic gold standard examination. We assessed 104 consecutive thoracoscopies. SMRP concentrations were obtained using an ELISA test. We had 34 mesotheliomas (25 epithelioid and 9 sarcomatoid), 35 pleural metastases, and 35 benign diseases. PE-SMRP were significantly higher in patients with epitheliomorphic mesothelioma (mean ± SD 46.55 ± 44.29 nM) than in patients with sarcomatoid mesothelioma (16.11 ± 25.02 nM; p = 0.061), pleural metastasis (7.52 ± 10.77 nM; p < 0.0001), or benign diseases (5.82 ± 8.86 nM; p < 0.0001). Using ROC curve analysis, PE-SMRP offered an AUC of 0.767 in its ability to differentiate between patients with mesothelioma and all other diagnoses. The diagnostic sensitivity and specificity of PE-SMRP for distinguishing mesothelioma from all other causes of pleural effusion, at a cut-off value of 19.6 nM, were 58.8 and 97.1 %, respectively. PE-SMRP higher than the assumed cut-off of 19.6 nM were observed in 18/25 (72.0 %) epitheliomorphic mesotheliomas, 2/9 (22.2 %) sarcomatoid mesotheliomas, 5/35 (14.3 %) pleural metastases, and 1/35 (2.9 %) benign diseases. We conclude that PE-SMRP adds some clinical information in the work-up of patients with a PE of unknown origin: (1) thoracoscopy should always be done in patients with a positive mesothelin; (2) a negative mesothelin does not exclude a malignant disease.
    No preview · Article · Sep 2013 · Medical Oncology
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    ABSTRACT: Background/Aim: Soluble mesothelin-related peptide (SMRP) is regarded as a biomarker of malignant pleural mesothelioma (MPM). Herein, we compared the diagnostic performances of SMRP in matched pleural effusion (PE-SMRP) and serum (S-SMRP). Diagnosis on pleural biopsies was performed for all patients including 43 with MPM, 23 with non-MPM pleural metastases (MTS) and 36 with benign (BNG) pleural diseases. SMRP was measured by a MesoMark ELISA (Cis-Bio International Gif/Yvette; France). Using the receiver operating characteristic (ROC) analysis, 12.70 and 1.08 nM were detected as cut-off values to optimal discrimination for PE-SMRP and S-SMRP, respectively. PE-SMRP showed a better diagnostic accuracy than S-SMRP in MPM vs. MTS+BNG (area under the ROC curve=81.6 vs. 70.5; sensitivity=69.8% vs. 46.5%; specificity=88.1% vs. 84.7%; diagnostic odds ratio (DOR)=17.1 vs. 4.8). In S-SMRP-negative patients, PE-SMRP maintained an acceptable performance (Sensitivity=47.8%; DOR=8.3; p=0.001), whereas in PE-SMRP-negative patients, S-SMRP performed very poorly (Sensitivity=15.4%; DOR=1.2; p=0.858). PE-SMRP detection has a superior diagnostic accuracy than S-SMRP detection in the diagnosis of MPM.
    Full-text · Article · Jun 2013 · Anticancer research
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    ABSTRACT: Soluble mesothelin-related peptide (SMRP) is regarded as an FDA approved biomarker for the diagnosis and monitoring of pleural malignant mesothelioma (MPM). We detected the SMRP levels in pleural effusions (PE) by means of an ELISA and analyzed their diagnostic relevance to differentiate MPM from benign pathology and from non-MPM pleural metastasis. Comparison with cytology in MPM-PE was also performed. We found that SMRP detection in MPM-PE can help the diagnosis of MPM and provide additional diagnostic value to cytology. We concluded that SMRP test may be incorporated into clinical practice of PE from patients suspicious for MPM.
    No preview · Article · Dec 2012 · Cancer Investigation
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    ABSTRACT: SESSION TYPE: Pleural BiomarkersPRESENTED ON: Monday, October 22, 2012 at 04:00 PM - 05:30 PMPURPOSE: Soluble mesothelin-related peptides (SMRP) are an FDA approved biomarker for the diagnosis and monitoring of pleural malignant mesothelioma (MPM). We report the SMRP levels in pleural fluid from a cohort of Italian patients and its utility in clinical management of MPM pleural effusions (MPM-PE).METHODS: We evaluated SMRP in 52 MPM-PE (35 epithelioid, 9 sarcomatoid, 4 biphasic, 2 desmoplastic, 2 papillary), 129 benign PE (B-PE) and 94 non-MPM pleural metastasis (Mts-PE) by means of the MesoMark ELISA kit. The diagnostic performance parameters were estimated through analysis of the ROC curve and the Youden's index was applied to obtain the biomarker's cut-off level of maximum discrimination. For each cut off, sensitivity (Se) and specificity (Sp) were calculated. The degree of correlation and P value were calculated using the diagnostic odds ratio (DOR) and the Chi-square test, respectively. Comparison between SMRP detection and cytology was also performed.RESULTS: The median SMRP levels was significantly higher in MPM-PE (28.2 nM) than in B-PE (3.2 nM) or Mts-PE (3.8 nM). MPM-PE yielded an AUC of 84.5 (p<0.001) vs B-PE and an AUC of 79.6 (p<0.001) vs Mts-PE. The cut off level of maximum discrimination between MPM vs each patient groups was 9.30 nmol/L. At this cut off value, we established Se=75%, Sp=93% for MPM-PE vs B-PE and SP=81% for MPM-PE vs Mts-PE. We found SMRP-positive cases (≥ cut off) in 38/52 (73.1%) MPM-PE, in 9/129 (7.0%) B-PE (DOR=40, p<0.001) and in 18/94 (19.1%) Mts-PE (DOR=13, p< 0.001). In 38/52 PE, with SMPR levels ≥ cut off, cytology was found positive in 11/38 (28.9%), negative in 20/38 (52.6%) and in 7/38 (18.4%) was considered suspicious. Moreover, in 4/15 (26.7%) cases of cytology-positive MPM-PE, the levels of SMPR resulted negative.CONCLUSIONS: SMPR detection in MPM-PE may provide additional diagnostic value to cytology. Combination of SMPR and cytology may increase diagnostic yield if both tests are performed together.CLINICAL IMPLICATIONS: SMPR analysis may be incorporated into clinical practice of MPM-PE in patients with suspected malignant mesothelioma.DISCLOSURE: The following authors have nothing to disclose: Anna Maria Carletti, Massimiliano Sivori, Paola Ferro, Enrico Battolla, Maria Franceschini, Franco Fedeli, Silvio Roncella, Pier Aldo CanessaNo Product/Research Disclosure InformationS.C. Pneumologia, ASL5 Spezzino, Ospedale San Bartolomeo, Sarzana, Italy.
    No preview · Article · Oct 2012 · Chest

  • No preview · Article · Jul 2012 · European Journal of Cancer
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    ABSTRACT: Background Malignant pleural mesothelioma (MPM) is an aggressive tumour usually associated with the presence of pleural effusion (PE). Differential diagnosis of the PE can be difficult because cytological analysis shows low sensitivity and specificity. Measurement of solubile mesothelin peptides (MS) has been reported to provide a complementary tool to aid in the diagnosis of MPM. The current study was undertaken to assess whether the levels of MS in PE may provide an additional diagnostic value to cytology and clinical practice. Methods MS was assessed by means of the MesoMark™ ELISA kit on a fraction of PE extracted by thoracentesis. Cytology was evaluated on fixed smears stained by Papanicolaou’s method. Results We evaluated MS in 52 MPM-PE and 223 PE of other origin. The geometric mean of MS levels in PE was significantly higher in MPM-PE (19.0 nmol/L) than in total other PE (3.5 nmol/L). The cut-off level was 9.30 nmol/L with an AUC of 82.0 (P-value <0.001), Sensitivity=75% and Specificity=87%. We found MS positive cases (-cut-off) in 38/52 (73%) of MPM-PE and MS in 27/223 (12%) of other PE (DOR 21.8; Pearson chisquare test P-value <0.001). Moreover, in the 5/23 (21.7%) cytology positive/suspicious MPM-PE the levels of SMRP were <9.30 nmol/L (cut-off). In contrast, in the 20/29 (69.0%) MPM-PE in which cytology was found negative the MS levels resulted positive. Conclusions MS detection in MPM-PE may provide additional diagnostic value to cytology. The MS test may be incorporated into clinical practice of PE from patients suspicious for MPM.
    No preview · Article · Jun 2012 · Rivista Italiana della Medicina di Laboratorio
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    ABSTRACT: human mammaglobin (hMAM) expression has been reported in pleural effusions (PE). The aim of this study was to assess the clinical relevance of hMAM mRNA in PE from patients who underwent thoracoscopy.
 A total of 288 patients with PE were studied, 155 of which were diagnosed with malignant and 133 with non-malignant diseases by thoracoscopy. Cells from PE were analyzed by nested hMAM RT-PCR. Statistical analyses were performed to evaluate the diagnostic performance parameters (DPP), the association between hMAM expression and benign or malignant status and the relative risk of cancer for patients with negative thoracoscopy showing hMAM positivity.
 hMAM mRNA was found in 68/288 (23.6%) PE samples of which 51 were from the 155 patients diagnosed with malignant diseases and 17 were from the 133 patients diagnosed with non-malignant diseases. A significant correlation between hMAM expression and malignancy was found (OR=3.04) and the DPP were as follows: sensitivity=32.9%, specificity=87.2%, accuracy=58.0%, positive predictive value=75.0% and negative predictive value=52.7%. Among the patients with negative thoracoscopy (n=133), 5/17 (29.4%) hMAM-positive patients had or developed a tumor during the 18-month follow up period, as compared to 10/116 (8.6%) hMAM-negative patients (relative risk of 4.6 for developing a malignancy).
 These findings suggest a possible application of hMAM RT-PCR detection in PE as to identify a false-negative thoracoscopy in non-specific pleuritis.
    No preview · Article · May 2012 · The International journal of biological markers
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    ABSTRACT: In breast cancer (BC), metastases to the central nervous system usually arise in women with advanced disease. Diagnosis of leptomeningeal (LM) metastasis is based on neurological symptoms, imaging studies and cytological detection of malignant cells in the cerebrospinal fluid (CSF). However, often these approaches are not sensitive enough to recognize leptomeninges involvement and subsequently to make a diagnosis of LM carcinomatosis. This study investigated the employment of reverse transcriptase-polymerase chain reaction (RT-PCR) for the human mammaglobin (hMAM) gene in a case of BC with cerebral metastases in which the involvement of the leptomeninges was in doubt. Amplification of hMAM mRNA was performed from CSF cells by RT-PCR. No amplification of hMAM was obtained from the CSF cells. RT-PCR for human mammaglobin mRNA of the CSF in BC patients with brain metastases may aid clinical determination of LM involvement and consequently the choice of the most effective therapy regimens for affected patients.
    No preview · Article · Mar 2011 · Anticancer research
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    ABSTRACT: So far discordant results regarding the significance of tumour cells circulating in peripheral blood (CTCs) of breast cancer (BC) patients have been reported. Our aim was to evaluate the association of indirect CTC detection by amplification of human mammaglobin (hMAM) gene expression with traditional prognostic markers of clinical outcome in BC at the time of diagnosis. Peripheral blood samples from 190 patients with invasive and 12 patients with in situ BC, before therapy and/or surgery, from 184 patients with benign breast disease and from 146 healthy volunteers were tested for hMAM expression by a nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Correlations between CTCs and age at diagnosis, tumour type and size, grading, lymph node involvement, oestrogen and progesterone receptor status, HER-2/neu expression and Ki-67/MIB-1 labelling index were assessed through the odds ratio (OR) point estimates, considering OR >2.0 or <0.5 as being clinically relevant. ORs and their corresponding 95% confidence limits (95% CL) were obtained by logistic regression analysis. Expression of hMAM was found only in peripheral blood of patients with invasive BC (9.5%) and multivariate logistic regression analysis indicated its association with lymph node involvement (pN1-pN3 vs. pN0, OR=5.6, 95% CL=1.4-22.6; p=0.009), tumour size (pT2-pT4 vs. pT1, OR=2.3, 95% CL=0.6-9.0; p=0.207) and negative ER status (OR=2.5, 95% CL=0.6-10.0; p=0.227). Our data show that CTC detection in invasive BC at the time of diagnosis is associated with poor prognosis and may also be used as an additional prognostic indicator.
    No preview · Article · Jun 2010 · Anticancer research
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    ABSTRACT: As was reported that human mammaglobin (hMAM) may be expressed in malignant pleural effusions (PEs), we investigated the relevance of hMAM reverse-transcriptase polymerase chain reaction (RT-PCR) for their diagnosis and determination of primary origin. Two hundred and twenty-eight malignant (132 male, 96 female) and 185 benign (132 male, 53 female) PEs were investigated. Statistical analyses evaluated the diagnostic performance parameters in all PEs and in cytologically negative malignant PEs, the association between hMAM and benign or malignant status by the direct index of correlation [diagnostic odds ratio (DOR)], chi test, and P value (P). In addition, the discriminative diagnostic power of hMAM expression, independently in breast cancer, lung cancer (LC), malignant mesothelioma (MM), and other cancers was evaluated. In the entire patient population, hMAM was detected in 45.6% and 5.4% of malignant and benign PEs, respectively, in the male group in 41.7% and 4.5% and in the female group in 51.0% and 7.5% of malignant and benign PEs, respectively. A statistically significant correlation between hMAM and malignancy was found in the entire population (DOR=14.68, P<0.001) and in the male (DOR=15.00, P<0.001) or female (DOR=12.77, P<0.001) groups. hMAM RT-PCR increased the diagnostic rate of malignant PEs as it allowed us to detect as malignant 32.1% of cytologically negative PEs. In female patients the positivity of hMAM indicated with higher probability (50.8%) the origin of PEs from breast cancer but lower probability from LC (17%), MM (9.4%), or other cancers (15.1%), whereas in male patients it indicated with similar probability (about 40%) the origin from LC or MM. Our results suggest that hMAM RT-PCR may provide information both in the diagnosis of PE and in the search for the primary site of neoplasia, either in male or female patients.
    No preview · Article · Jun 2010 · Diagnostic molecular pathology: the American journal of surgical pathology, part B
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    ABSTRACT: The present study investigates the diagnostic significance of human mammaglobin (hMAM) mRNA expression in pleural effusions (PE) from breast cancer (BC) patients. Two hundred and fifty PE samples, including 32 from patients who had diagnosis of BC, 116 from patients with other cancers, and 102 from patients with benign diseases, were subjected to nested reverse-transcription polymerase chain reaction (RT-PCR) for hMAM, and the results were compared with conventional cytology. hMAM was found expressed in 76/250 (30.4%) total PE and in 23/28 (sensitivity of 82.1%) of the PE subgroup owing to metastasis from BC. The specificity for hMAM detection method was 75.7%, whereas accuracy, positive predictive value, and negative predictive value were 76.4%, 30.3%, and 97.1%, respectively. hMAM was also detected in 46/116 (39.6%) PE specimens from other types of cancer and in 7/102 (6.8%) from benign diseases. Comparative analysis of RT-PCR and cytology showed that 14 PE samples from metastatic BC (50%) were positive by both PCR and cytology, 9 (32.1%) were positive only by PCR and 5 (17.9%) were negative by both tests, whereas no cases were found of positive cytology with negative PCR. RT-PCR increased sensitivity of BC effusion detection to 32.1% (McNemar test, P=0.004). We demonstrated that RT-PCR for hMAM test was more sensitive than cytomorphology suggesting that, although hMAM is not BC specific, it may be useful in adjunct to cytology for the routine screening of malignant BC effusions.
    No preview · Article · Apr 2008 · Diagnostic Molecular Pathology