Open Access Review Article

Malignant Pleural Mesothelioma : Current Perspectives in Early Detection and Diagnosis

Attapon Cheepsattayakorn1,2*, Ruangrong Cheepsattayakorn3, Supawan Manosoontorn4 and Vijaya Bhakskara Reddy Mutha5

110th Zonal Tuberculosis and Chest Disease Center, Thailand

3Department of Pathology, Faculty of Medicine, Chiang Mai University, Thailand

2,4,5Faculty of Public Health, St. Theresa International College, Thailand

Corresponding Author

Received Date: December 11, 2019;  Published Date: January 10, 2020


The objectives of this study are to review epidemiology, novel methods of detection, and novel diagnostics of malignant pleural mesothelioma (MPM) in the literature that were published between 1977 and 2019. Malignant pleural mesothelioma associated with prolonged respirable-asbestosfiber exposure is a rare cancer with constantly increasing incidence and poor prognosis due to lacking the effective treatment options. The median survival ranges from 8 to 14 months. Sarcomatoid histological subtype has the worst prognosis. Video-assisted thoracoscopy plus mediastinoscopy is the current gold standard for staging malignant pleural mesothelioma and is superior to computerized tomography of the chest for assessing the tumor size and suspected nodal metastases. Several circulating biomarkers are detected in MPM patients, such as mesothelin, osteopontin, fibulin-3, high mobility group B1, vascular endothelial growth factor, reactive oxygen species, reactive nitrogen species, micro-ribonucleic acids, tumor deoxyribonucleic acid, etc. In conclusion, there is potential for the development of biomarkers and radiological imaging in the years to come. Its incidence is expected to decrease in the next decade.

Keywords: Pleural; Mesothelioma; Malignant; Diagnosis; Epidemiology

Abbreviations: BALF : Bronchoalveolar lavage; BAP1 : BRCA-associated protein 1; CFAP45 : Cilia and flagella associated protein 45; CT : Computed tomography; CTCs : Circulating tumor cells; ctDNA : circulating tumor Deoxyribonucleic acid; DNA : Deoxyribonucleic acid; FDG : 18-fluoro-deoxyglucose; HMGB1 : High Mobility Group B1 ; miRNAs : micro-Ribonucleic acids; MPM : Malignant pleural mesothelioma; MRI : Magnetic resonance imaging ; MSLN : Mesothelin; PDGF : Platelet-derived growth factor; PET-CT : Positron-emission technology-computed tomography; RNS : Reactive nitrogen species; ROS : Reactive oxygen species; RR2 : Ryanodine receptor 2; SETDB1 : Set domain bifurcated 1; SETD2 : Set domain containing 2; SMRP : Soluble mesothelin-related peptide; TGF-β : Tumor growth factor-β ; TNM : Tumor-nodes-metastases; UICC : the Union for International Cancer Control ; UK : United Kingdom; ULK2 : Unc-like autophagy activating kinase; USA : United States of America; US FDA : United States Food and Drug Administration; VATS : Video-assisted thoracoscopic surgery; VEGF : Vascular endothelial growth factor

Objectives of the Study

The objectives of this study are to review epidemiology, novel methods of detection, and novel diagnostics of malignant pleural mesothelioma (MPM) in the literature that were published between 1977 and 2019.


Malignant pleural mesothelioma, a tumor originated from the submesothelial or mesothelial cells of pleura, pericardium, or peritoneum accounts for more than 80 % arising from the pleura that the majority are male patients [1,2]. MPM, a rare cancer with increasing incidence and poor prognosis because of lacking the effective therapeutic interventions [1,3-4]. MPM is associated with previous long-term asbestos exposure of about 40 years of latency period [5-9]. The total incidence is highest in the UK and USA whereas the global incidence has increased constantly over the past decade and is predicted to reach the estimated peak in 2020 [5,6]. The median survival of MPM ranges from 8 to 14 months from the diagnosis [5-7,10]. Male is predominant of 4 : 1 [10]. Four main histological subtypes of MPM are classified as the following : 1) epithelioid ( most favorable prognosis with a median survival of 13.1 months), 2) sarcomatoid (worst outcomes with a median survival of 4 months), 3) biphasic or mixed, and 4) desmoplastic [5, 6,10].


Prolonged exposure to respirable asbestos fibers triggers an increase in inflammatory cytokines and reactive oxygen species (ROS) in the pleural microenvironment, both of which facilitate MPM carcinogenesis [11,12]. Naturally, asbestos occurs in the form of silicate mineral with two different forms : 1) curly serpentine fibers of chrysotile or “ white ” asbestos and 2) sharp, needle-like fibers of amphibole asbestos. Amphibole asbestos is divided into 2.1) crocidolite (blue) asbestos, 2.2) amosite (brown) asbestos, 2.3) anthophyllite, 2.4) actinolite, and 2.5) tremolite. The risk of MPM development is associate with the type of fibers and heaviness and duration of exposure [5]. Nevertheless, MPM is characterized by a low mutation load [13], with the most frequently mutated genes involved in MPM pathogenesis, “ tumor suppressors (BAP1, CDKN2A, LATS2, NF2) [14]. After asbestos fibers are inhaled and migrate to the pleural space causing pleural irritation and a repeated cycle of tissue damage and repair. Asbestos fibers that penetrate mesothelial cells that cause cell mitosis interference, generating DNA mutation, and altering chromosome structure. These mesothelial cells release inflammatory cytokines, such as plateletderived growth factor (PDGF), tumor growth factor-β (TGF-β), and vascular endothelial growth factor (VEGF) that facilitate tumor growth [9]. Asbestos fibers also induce the phosphorylation various protein kinases (extracellular signal-regulated kinase 1 and 2 and mitogen-activated protein) that increases the expression of protooncogenes and facilitating abnormal cellular proliferation [15]. In PMP tumor, there is reduced expression of key molecules in the p53 tumor-suppressor gene pathway (p14, p16, and NF2-MERLIN) [15]. There are deletions and loss mutations of BAP1 (BRCAassociated protein 1), CFAP45 (cilia and flagella associated protein 45), DDX3X, DDX51, RR2 (ryanodine receptor 2), SETDB1 (set domain bifurcated 1), SETD2 (set domain containing 2), and ULK2 (unc-like autophagy activating kinase) [16]. Nevertheless, MPM has a low frequency of protein-altering mutations, approximately 25 mutations per tumor [17] and contributing to the limitations of the potential for molecular targeted therapy [18].

Detection and Diagnosis

Chest radiological imaging should be performed in all MPMsuspected patients for diagnostic and staging information. Characteristically radiological findings may be nodular pleural thickening, pleural plaques, a localized pleural-mass lesion, pleural effusion, irregular fissural thickening, or loss of hemithoracic volume. Nevertheless, further radiologically imaging tools, such as bedside chest ultrasonography, computed tomographic imaging are usually required due to insensitive and nonspecific chest radiographic features in general [19-22]. Positron-emission technology-computed tomography (PET-CT) combines highresolution computed tomographic (CT) scanning injected with a radioactive metabolic tracer (such as 18-fluoro-deoxy-glucose (FDG)) or magnetic resonance imaging (MRI) [23-25]. Nevertheless, PET-CT has low sensitivity for the diagnosis of extrapleural lesions due to its poor spatial resolution [26]. In addition to CT scanning of the chest, surgical information by video-assisted thoracoscopic surgery (VATS) plus mediastinoscopy which is the current gold standard for staging in MPM and is superior to CT for assessing tumor size and suspected nodal metastasis [27, 28] is the consensus by using the International Mesothelioma Interest Group staging classification [29] whereas the European Pneumological Society [30] recommends using the tumor-nodes-metastases (TNM) classification of the Union for International Cancer Control (UICC) [31]. VATS reveal the sensitivity and specificity of 95 %-98 % and 100 %, respectively and enables the removal of specimens under visual observation, as well as pleurodesis in the same procedure [28]. VATS also enable the assessment of its respectability [32]. By pleural puncture and cytological diagnosis, tumor cells are identified in pleural effusion more than 50 % of patients with MPM, with the likelihood of positive cytology depending on the MPM subtype with the limited cytological diagnosis [33]. Percutaneous needle biopsy without image guidance reveals the sensitivity and specificity of 7 %-47 % and 100 %, respectively [28].

There are several circulating tumor proteins identified in patients with MPM, such as mesothelin (MSLN, a cell-surface glycoprotein expressed by mesothelial cells) [34-36], osteopontin (an integrin-binding protein implicated in cell-matrix interaction and overexpressed in several types of cancers) [37,38], and fibulin-3 (a secreted glycoprotein implicated in cell proliferation and migration correlated with advanced disease, also identified in pleural fluid) [39,40]. Soluble mesothelin-related peptide (SMRP), a soluble form of mesothelin is secreted by the tumor cells into the blood circulation [41-43]. SMRP seems to be effective in predicting response to chemotherapy and patient survival although it is not specific for MPM and cannot be considered an early diagnostic biomarker for MPM surveillance program [41, 44- 48]. Several studies revealed that plasma osteopontin is a more reliable and stable biomarker than serum osteopontin and the data involving its diagnostic accuracy are inadequate [49-51]. Combined measurement of circulating SMRP and osteopontin is not more informative than measurement of circulating SMRP alone [49,50,52,53]. Several previous studies demonstrated that fibulin-3 was not beneficial for differentiating patients with MPM from patients affected by other diseases [54] and was not effective as mesothelin [55]. Other biomarkers for detecting MPM are inflammatory and angiogenic factors (High Mobility Group B1 (HMGB1) and VEGF), biomarkers of oxidative stress (Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS)), circulating micro-ribonucleic acids (miRNAs), circulating tumor deoxyribonucleic acid (ctDNA), circulating methylated deoxyribonucleic acid (circulating methylated DNA), and circulating tumor cells (CTCs). A previous study indicated that HMGB1 and its receptors were highly expressed in MPM cell lines and tissues [56]. VEGF, a key stimulator of tumor neoangiogenesis, is overexpressed in MPM tissues [57-59]. In comparison to patients with lung cancer or non-malignant pleural diseases, circulating VEGF levels are increased in pleural effusions of patients with MPM [60]. ROS and RNS are key mediators of asbestos toxicity [61].

Bronchoalveolar lavage (BALF) of patients with asbestos exposure demonstrated an increase in various biomarkers of inflammation and altered ROS and iron homeostasis (i.e., iron, lactoferrin, ferritin, transferrin, and transferrin receptors) compared to controls [62]. A previous study on the levels of miR-103a-3p and miR-30e-3p in extracellular vesicles demonstrated that the combination of these two biomarkers discriminated patients with MPM from asbestosexposed controls with a sensitivity of 95.5 % and specificity of 80 % and were confirmed by normalizing the data to RNU48, miR-99a, miR-638, miR-720, and miR-1274a [63]. In consideration, these miRNAs could be biomarkers of asbestos exposure rather than disease. Upregulation of miR-2053 could be a good prognostic biomarker of MPM [64]. Detection of ctDNA variants in patients with MPM could be a potential biomarker for the diagnosis of MPM [65-67]. Detection of changes in ctDNA methylation could be an early diagnostic and prognostic tool of MPM [68]. CTCs counts in the blood circulation is very low at the early stage and increases in advanced stage of cancer [69 ]. “ CTC-chip ” test that developed by Chikaishi et al demonstrated better performance than CELLSEARCH® test that is approved by the United States Food and Drug Administration (US FDA) [70,71].


Several circulating biomarkers are investigated for screening and detection of MPM, such as mesothelin, osteopontin, fibulin-3, HMGB1, VEGF, ROS, RNS, miRNAs, ctDNA [34-68]. Additionally, “ CTC-chip ” test developed by Chikaishi et al revealed better results than “ CELLSEARCH® ” test that approved by the US FDA. CTCs counts increases in the MPM patients with advanced stage [69]. The mentioned miRNAs are beneficial biomarkers of asbestos exposure rather than advanced stage MPM. Detection of changing ctDNA methylation could be beneficial in early diagnosis and prognosis of MPM [68] , whereas upregulation of miR-2053 could be a good prognostic biomarker of MPM [64]. For detection of asbestos toxicity, both ROS and RNS are the key mediators [61].


MPM, a complex disease can cause important morbidity and mortality. MPM remains a diagnostic and therapeutic challenge ambulatory and in-hospital care. There is potential for the development of biomarkers and radiological imaging in the years to come. Its incidence has been constant in recent years and expect to decrease in the next decade.

Authors Contributions

Dr. Attapon Cheepsattayakorn conducted the study framework and wrote the manuscript. Associate Professor Dr. Ruangrong Cheepsattayakorn contributed to scientific content and assistance in manuscript writing. Both authors read and approved the final version of the manuscript. Both Assistant Professor Dr. Supawan Manosoontorn and Dr. Vijaya Bhakskara Reddy Mutha were responsible for the reference citation search.



Conflict of Interest

No conflict of interest.


  1. Delgermaa V, Takahashi  K, Park  E, Le  G, Hara  T, Sorahan  T (2011)  Global  mesothelioma  deaths  reported  to  the  World  Health  Organization. 89 : 716-724, 724a-c.
  2. Woitowitz H, Hillerdal  G, Galvarezos  A, Berghäuser  K, Rödels-perger  K, et  al. (1993)   Risko  und  Einflussfaktoren  des  diffusen  malignen  Mesotheliomas (DMM)  Forschungsberichtsrehe  FB  698  Bundesanstalt  für  Arbeitsschutz.
  3. Robinson BM. (2012)  Malignant  pleural  mesothelioma : an  epidemiological  perspective.  Ann  Cardiothorac  Surg  1 : 491-496.
  4. Vogelzang NJ, Rusthven  JJ, Symanowski  J, Denham  C, Kaukel  E, et al. (2003)  Phase  III  study  of  pemetrexed  in  combination  with  cisplatin  versus  cisplatin  alone  in  patients  with  malignant  pleural  mesothelioma.  J  Clin  Oncol  21 : 2636-2644.
  5. British Thoracic  Society  Standards  of  Care  Committee (2007).  BTS  statement  on  malignant  mesothelioma  in  the  UK, 2007. Thorax  62 : Suppl 2, ii1-ii19. 
  6. Scherpereel A, Astoul  P, Baas  P, Berghmans T, Clayson H, et  al. (2010)  Guidelines  of  the  European  Respiratory  Society  and  the  European  Society  of  Thoracic  Surgeons  for  the  management  of  malignant  pleural  mesothelioma.  Eur  Respir  J  35 : 479-495.
  7. Yates D, Corrin  B, Stidolph  P, Browne K (1997)  Malignant  mesothelioma  in  south  east  England : clinicopathological  experience  of  272  cases.  Thorax  52 : 507-512. 
  8. Howel D, Arblaster  L, Swinburne  L, Schweiger M, Renvoize E, et al. (1997)  Routes  of  asbestos  exposure  and  the  development  of  mesothelioma  in  an  English  region.  Occup  Environ  Med 54 :403-409.
  9. Sekido Y (2013)  Molecular  pathogenesis  of  malignant  mesothelioma.  Carcinogenesis  34 : 1413-1419.  
  10. Beckett P, Edwards  J, Fennell  D, Hubbard R, Woolhouse I, et  al. (2015)  Demographics, management  and  survival  of  patients  with  malignant  pleural  mesothelioma  in  the  National  Lung  Cancer  Audit  in  England  and  Wales.  Lung  Cancer.  88 : 344-348.  
  11. Carbone M, Yang  H (2012)  Molecular  pathways : targeting  mechanisms  of  asbestos  and  erionite  carcinogenesis  in  mesothelioma.  Clin  Cancer  Res  18 : 598-604. 
  12. Bograd AJ, Suzuki  K, Vertes  E, Colovos  C, Morales  EA, et  al. (2011)  Immune  response  and  immunotherapeutic  interventions  in  malignant  pleural  mesothelioma.  Cancer  Immunol  Immunother  60 : 1509-1527.
  13. Chalmers ZR, Connelly  CF, Fabrizio  D, Gay  L, Ali  SM, et  al. (2017)  Analysis  of  100,000  human  cancer  genomes  reveals  the  landscape  of  tumor  mutational  burden.  Genome  Med  9 : 34. 
  14. Bott M, Brevet  M, Taylor  BS, Shimizu  S, Ito  T, et  al. (2011)  The  nuclear  deubiquitinase  BAP1  is  commonly  inactivated  by  somatic  mutations  and  3p21.1  losses  in  malignant  pleural  mesothelioma.  Nat  Genet  43 : 668-672.   
  15. Robinson BW, Lake  RA (2005)  Advances  in  malignant  mesothelioma.  N  Eng  J  Med  353 : 1591-1603.
  16. Illei PB, Rusch  VW, Zakowski  MF, Ladanyi M (2003)  Homozygous  deletion  of  CDKN2A  and  codeletion  of  the  methylthioadenosine  phosphorylase  gene  in  the  majority  of  pleural  mesotheliomas.  Clin  Cancer  Res  9 : 2108-2113.
  17. Guo G, Chmielecki  J, Goparaju  C, Heguy A, Dolgalev I, et  al. (2015)  Whole-exome  sequencing  reveals  frequent  genetic  alterations  in  BAP1, NF2, CDKN2A, and  CUL1  in  malignant  pleural  mesothelioma.  Cancer  Res  75 : 264-269.
  18. Torti D, Trusolino  L (2011)  Oncogene  addiction  as  a  foundational  rationale  for  targeted  anti-cancer  therapy : promises  and  perils.  EMBO  Mol  Med  3 : 623-636.     
  19. Salonen O, Kivisaari  L, Standertskjöld-Nordenstam  CG, Somer K, Mattson K, et al. (1986)  Computed  tomography  of  pleural  lesions  with  special  reference  to  the  mediastinal  pleura.  Acta  Radiologica  Diagnosis (Sweden)  27 : 527-531. 
  20. Havelock T, Teoh  R, Laws  D, Gleeson F (2010)  Pleural  procedures  and  thoracic  ultrasound :  British  Thoracic  Society  pleural  disease  guidelines  2010.  Thorax  65 : Suppl 2 : i61-i76. 
  21. Qureshi NR, Rahman  NM, Gleeson  FV (2009)  Thoracic  ultrasound  in  the  diagnosis  of  malignant  pleural  effusion.  Thorax  64 : 139-143.
  22. Hierholzer J, Luo  L, Bittner  RC, Stroszczynski C, Schröder RJ, et  al. (2000)  MRI  and  CT  in  the  differential  diagnosis  of  pleural  disease.  Chest  J  118 : 604-609.       
  23. Benard F, Sterman  D, Smith  RJ, Kaiser LR, Albelda SM, et al. (1998)  Metabolic  imaging  of  malignant  pleural  mesothelioma  with  fluorodeoxyglucose  positron  emission  tomography.  Chest  J.  114 : 713-722.
  24. Yildirim H, Metintas  M, Entok  E, Ak G, Ak I, et  al. (2009)  Clinical  value  of  fluorodeoxyglucose-positron  emission  tomography/computed  tomography  in  differentiation  of  malignant  mesothelioma  from  asbestos-related  benign  pleural  disease : an  observational  pilot  study.  J  Thorac  Oncol  4 : 1480-1484. 
  25. Treglia G, Sadeghi  R, Annunziata  S, Lococo F, Cafarotti S, et  al. (2014)  Diagnostic  accuracy  of  18F-FDG-PET  and  PET/CT  in  the  differential  diagnosis  between  malignant  and  benign  pleural  lesions : a  systematic  review  and  meta-analysis.  Acad  Radiol  21 : 11-20.  
  26. Steward D, Waller  D, Edwards  J,  Jeyapalan K, Entwisle J (2003)  Is  there  a  role  for  pre-operative  contrast-enhanced  magnetic  resonance  imaging  for  radical  surgery  in  malignant  pleural  mesothelioma ?  Eur  J  Cardiothorac  Surg  24 : 1019-1024. 
  27. Heelan R, Rusch  V, Begg  C, Panicek DM, Caravelli JF, et  al. (1999)  Staging  of  malignant  pleural  mesothelioma: comparison  of  CT  and  MR  imaging.  Am  J  Roentgenol  172 : 1039-1047. 
  28. Attanous R, Gibbs  A (2006)  The  comparative  accuracy  of  different  pleural  biopsy  techniques  in  the  diagnosis  of  malignant  mesothelioma.  Histopathol  53 : 340-344. 
  29. Rusch VW (1995)  A  proposed  new  international  TNM  staging  system  for  malignant  pleural  mesothelioma.  Chest.  108 : 1122-1128.
  30. Scherpereel A, Astoul  P, Baas  P, Berghmans T, Clayson H, et  al. (2010)  Guidelines  of  the  European  Respiratory  Society  and  the  European  Society  of  Thoracic  Surgeons  for  the  management  of  malignant  pleural  mesothelioma.  Eur  Respir  J.  35 : 479-495. 
  31. Wittekind C, Meyer  H (2010)  TNM  Klassifikation  maligner  Tumoren.  7.  Auflage.  Weinlheim : Wiley-VCH.   
  32. Hasegawa S, Kondo  N, Matsumoto  S, Takuwa T, Hashimoto M, et  al. (2012)  Practical  approaches  to  diagnose  and  treatment  to  malignant  pleural  mesothelioma :  a  proposal  for  diagnostic  total  parietal  pleurectomy.  Int  J  Clin  Oncol.  17 : 33-39.  
  33. Husain A, Colby  T, Ordonez  N, Allen TC, Attanoos RL, et  al. (2012)  Guidelines  for  pathologic  diagnosis  of  malignant  mesothelioma.  Arch  Pathol  Lab  Med.  136 :  1-21.
  34. Pastan I, Hassan  R (2014)  Discovery  of  mesothelin  and  exploiting  it  as  a  target  for  immunotherapy.  Cancer  Res.  74 : 2907-2912. 
  35. Chang K, Pai  LH, Batra  JK, Pastan I, Willingham MC (1992)  Characterization  of  the  antigen (CAK1)  recognized  by  monoclonal  antibody  K1  present  on  ovarian  cancers  and  normal  mesothelium.  Cancer  Res.  52 : 181-186.
  36. Chang K, Pai  LH, Pass  H, Pogrebniak HW, Tsao MS, et  al. (1993)  Monoclonal  antibody  K1  reacts  with  epithelial  mesothelioma  but  not  with  lung  adenocarcinoma.  Lung  Cancer.  8 : 336.
  37. Coppola D, Szabo  M, Boulware  D, Muraca  P, Alsarraj  M, et  al. (2004)  Correlation  of  osteopontin  protein  expression  and  pathological  stage  across  a  wide  variety  of  tumor  histologies.  Clin  Cancer  Res.  10 : 184-190. 
  38. Pass HI, Lott  D, Lonardo  F, Harbut  M, Liu  Z, et  al. (2005)  Asbestos  exposure, pleural  mesothelioma, and  serum  osteopontin  levels.  N  Engl  J  Med.  353 : 1564-1573.  
  39. Creaney J, Dick  IM, Robison  BW (2015)  Comparison  of  mesothelin  and  fibulin-3  in  pleural  fluid  and  serum  as  markers  in  malignant  mesothelioma.  Curr  Opin  Pulm  Med  21 : 352-356.
  40. Pass HI, Levin  SM, Harbut  MR (2012)  Fibulin-3  as  a  blood  and  effusion  biomarker  for  pleural  mesothelioma.  N  Engl  J  Med  367 : 1417-1427.
  41. Scholler N, Fu  N, Yang  Y, Ye  Z, Goodman  GF, et  al. (1999)  Soluble  member(s)  of  the  mesothelin/megakaryocyte potentiating  factor  family  are  detectable  in  sera  from  patients  with  ovarian  carcinoma.  Proc  Natl  Acad  Sci  USA  96 : 11531-11536.
  42. Hollevoet K, Reitsma  JB, Creaney  J, Grigoriu  BD, Robinson  BW, et  al. (2012)  Serum  mesothelin  for  diagnosing  malignant  pleural  mesothelioma :  an  individual  patient  data  meta-analysis.  J  Clin  Oncol  30 : 1541-1549. 
  43. Rai AJ, Flores  RM, Mathew  A, Gonzalez-Espinoza  R, Bott  M, et  al. (2010)  Soluble  mesothelin-related  peptides (SMRP)  and  osteopontin  as  protein  biomarkers  for  malignant  mesothelioma :  analytical  validation  of  ELISA-based  assays  and  characterization  at  mRNA  and  protein  levels.  Clin  Chem  Lab  Med  48 : 271-278.
  44. Beyer HL, Geschwindt  RD, Glover  CL, Tran  L, Hellstrom  I, et  al. (2007)  A  potential  test  for  malignant  pleural  mesothelioma.  Clin  Chem  53 : 666-672.
  45. Ordonnez NG (2003)   Value  of  mesothelin  immunostaining  in  the  diagnosis  of  mesothelioma.  Mod  Pathol  16 : 192-197.
  46. Cristaudo A, Foddis  R, Vivaldi  A, Guglielmi  G, Dipalma  N, et  al. (2007)  Clinical  significance  of serum  mesothelin  in  patients  with  mesothelioma  and  lung  cancer.  Clin  Cancer  Res  13 : 5076-5081.
  47. Grigoriu BD, Scherpereel  A, Devos  P, Chahine  B, Letourneux  M, et al. (2007)  Utility  of  osteopontin  and  serum  mesothelin  in  malignant  pleural  mesothelioma  diagnosis  and  prognosis  assessment.  Clin  Cancer  Res  13 : 2928-2935.
  48. Schneider J, Hoffmann  H, Dienemann  H, Herth  FJ, Meister  M, et  al. (2008)  Diagnostic  and  prognostic  value  of  soluble  mesothelin-related  proteins  in  patients  with  malignant  pleural  mesothelioma  in comparison  with  benign  asbestosis  and  lung  cancer.  J  Thorac  Oncol  3 : 1317-1324.
  49. Cristaudo A, Bonotti  A, Simonini  S, Vivaldi  A, Guglielmi  G, et  al. (2011)  Combined  serum  mesothelin  and  plasma  osteopontin  measurements  in  malignant  pleural  mesothelioma.  J  Thorac  Oncol  6 : 1587-1593.
  50. Creaney J, Yeoman  D, Musk  AW, de  Klerk  N, Skates  SJ, et al. (2011)  Plasma  versus  serum  levels  of  osteopontin  and  mesothelin  in  patients  with  malignant  mesothelioma-which  is  best ?  Lung  Cancer  74 : 55-60. 
  51. Foddis R, Bonotti  A, Landi  S, Fallahi  P, Guglielmi  G, et al. (2018)  Biomarkers  in  the  prevention  and  follow-up  of  workers  exposed  to  asbestos.  J  Thorac  Dis  10 : S360-S368.         
  52. Hollevoet K, Nackaerts  K, Gosselin  R, de  Wever  W, Bosquee  L, et  al. (2011)  Soluble  mesothelin, megakaryocyte potentiating  factor, and  osteopontin  as  markers  of  patient  response  and  outcome  in  mesothelioma.  J  Thorac  oncol  6 : 1930-1937. 
  53. Wheatley-Price P, Yang  B, Patsios  D, Patel  D, Ma  C, et  al. (2010)   Soluble  mesothelin-related  peptide  and  osteopontin  as  markers  of  response  in  malignant  mesothelioma.  J  Clin  Oncol  28 : 3316-3322.
  54. Kirschner MB, Pulford  E, Hoda  MA, Rozsas  A, Griggs  K, et  al. (2015)  Fibulin-3  levels  in  malignant  pleural  mesothelioma  are  associated  with  prognosis  but  not  diagnosis.  Br  J  Cancer  113 : 963-969.
  55. Creaney J, Dick  IM, Meniawy  TM, Leong  SL, Leon  JS, et  al. (2014)  Comparison  of  fibulin-3  and  mesothelin  as  markers  in  malignant  mesothelioma.  Thorax  69 : 895-902.  
  56. Jube S, Rivera  ZS, Bianchi  ME, Powers  A, Wang  E, et  al. (2012)  Cancer  cell  secretion  of  the  DAMP  protein  HMGB1  supports  progression  in  malignant  mesothelioma.  Cancer  Res  72 : 3290-3301. 
  57. Kumar-Singh S, Weyler  J, Martin  MJ, Vermeulen  PB, van  Marck  E (1999) Angiogenic  cytokines  in  mesothelioma : a  study  of  VEGF, FGF-1  and  -2, and  TGF-beta  expression.  J  Pathol  189 : 72-78.
  58. Strizzi L, Catalano  A, Vianale  G, Orecchia  S, Casalini  A, et  al. (2001)  Vascular  endothelial  growth  factor  is  an  autocrine  growth  factor  in  human  malignant  mesothelioma.  J  Pathol  193 : 468-475.
  59. Demirag F, Unsal  E, Yilmaz  A, Caglar  A (2005)  Prognostic  significance  of  vascular  endothelial  growth  factor, tumor  necrosis, and  mitotic  activity  index  in  malignant  pleural  mesothelioma.  Chest  128 : 3382-3387.
  60. Hirayama N, Tabata  C, Tabata  R, Maeda  R, Yasumitsu  A, et  al. (2011)  Pleural  effusion  VEGF  levels  as  a  prognostic  factor  of  malignant  pleural  mesothelioma.  Respir  Med  105 : 137-142.
  61. Shukla A, Gulumian  M, Hei  TK, Kamp  D, Rahman  Q, et  al. (2003)  Multiple  roles  of  oxidants  in  the  pathogenesis  of  asbestos-induced  diseases.  Free  Radic  Biol  Med  34 : 1117-1129. 
  62. Ghio AJ, Stonehuerner  J, Richards  J, Devlin  RB (2008)  Iron  homeostasis  in  the  lung  following  asbestos  exposure.  Antioxid  Redox  Signal  10 : 371-377. 
  63. Cavalleri T, Angelici  L, Favero  C, Dioni  L, Mensi  C, et  al. (2017)  Plasmatic  extracellular  vesicle  microRNAs  in  malignant  pleural  mesothelioma  and  asbestos-exposed  subjects  suggest  2-miRNA  signature  biomarkers  of  disease.  PLoS  ONE  12 : e0176680. 
  64. Matboli M, Shafei  AE, Ali  MA, Gaber  AI, Galal  A, et  al. (2019)  Clinical  significance  of  serum  DRAM1  mRNA, ARSA  mRNA, has-miR-2053  and  lncRNA-RP1-86D1.3  axis  expression  in  malignant  pleural  mesothelioma.  J  Cell  Biochem  120 : 3203-3211.   
  65. Fan HC, Blumenfeld  YJ, Chikara  U, Hudgins  L, Quake  SR, et  al. (2010)  Analysis  of  the  size  distributions  of  fetal  and  maternal  cell-free  DNA  by  paired-end  sequencing.  Clin  Chem  56 : 1279-1286.
  66. Corcoran RB, Chabner  BA (2018)  Application  of  cell-free  DNA  analysis  to  cancer  treatment.  N  Engl  J  Med  379 : 1754-1765.
  67. Leon SA, Shapiro  B, Sklaroff  DM, Yaros  MJ (1977)  Free  DNA  in  the  serum  of  cancer  patients  and  the  effect  of  therapy.  Cancer  Res  37 : 646-650.
  68. Kanherkar RR, Bhatia-Dey  N, Csoka  AB (2014)  Epigenics  across  the  human  lifespan.  Front  Cell  Dev  Biol  2 : 49. 
  69. Young R, Pailler  E, Billiot  F, Drusch  F, Barthelemy  A, et  al. (2012)  Circulating  tumor  cells  in  lung  cancer.  Acta  Cytol  56 : 655-660. 
  70. Su DW, Nieva  J (2017)  Biophysical  technologies  for  understanding  circulating  tumor  cell  biology  and  metastasis.  Trans  Lung  Cancer  Res  6 : 473-485. 
  71. Chikaishi Y, Yoneda  K, Ohnaga  T, Tanaka  F (2017)  EpCAM-independent  capture  of  circulating  tumor  cells  with  a  “ universal  CTC-chip ”.  Oncol  Rep  37 : 77-82.
Signup for Newsletter
Scroll to Top