Tumor Biology

, Volume 34, Issue 6, pp 3529–3536 | Cite as

Clinical significance of serum M30 and M65 levels in metastatic pancreatic adenocarcinoma

  • Faruk Tas
  • Senem Karabulut
  • Elif Bilgin
  • Fatma Sen
  • Ibrahim Yildiz
  • Didem Tastekin
  • Rumeysa Ciftci
  • Derya Duranyildiz
Research Article


M30 and M65 are relatively new assays that detect different circulating forms of the epithelial cell structural protein cytokeratin 18. This study was conducted to investigate the serum levels of M30 and M65 in patients with metastatic pancreatic adenocarcinoma (MPA) and the relationship with tumor progression and known prognostic parameters. Twenty-six patients with MPA were investigated. Serum samples were obtained on first admission before treatment and follow-up. Both serum M30 and M65 levels were determined using enzyme-linked immunosorbent assay. The median age at diagnosis was 59 years, range 32–80 years; 14 patients were men. All patients had metastatic stage, and most (n = 21, 81 %) had hepatic metastasis. The baseline levels of both serum M30 and serum M65 were significantly higher in patients with MPA than those in the control group (p < 0.001, for both assays). Serum M65 level was only significantly higher in the patients with elevated serum LDH levels than in others with normal serum LDH levels (p = 0.03). For serum M30 levels, no correlation was found. The significant relationship was found between the serum levels of M30 and M65 (r s = 0. 926, n = 26, p < 0.001, Spearman’s correlation). The median survival for all patients was 31.7 ± 2.2 weeks (95 % CI = 27.31–36.08). Although only the serum LDH level was found to be a significant prognostic factor (p = 0.01), neither serum M30 nor serum M65 had significant effect on survival (p = 0.28 and p = 0.15, respectively). In conclusion, although both serum levels of M30 and M65 assays were found to be of diagnostic value, no predictive and prognostic values were determined in MPA patients.


M30 M65 Pancreatic cancer Metastatic Survival 


Conflicts of Interest



  1. 1.
    Chu PG, Weiss LM. Keratin expression in human tissues and neoplasms. Histopathol. 2002;40:403–39.CrossRefGoogle Scholar
  2. 2.
    Cummings J, Hodgkinson C, Odedra R, Sini P, Heaton SP, Mundt KE, et al. Preclinical evaluation of M30 and M65 ELISAs as biomarkers of drug induced tumor cell death and antitumor activity. Mol Cancer Ther. 2008;7:455–63.PubMedCrossRefGoogle Scholar
  3. 3.
    De Haas EC, di Pietro A, Simpson KL, Meijer C, Suurmeijer AJH, Lancashire LJ, et al. Clinical evaluation of M30 and M65 ELISA cell death assays as circulating biomarkers in a drug-sensitive tumor, testicular cancer. Neoplasia. 2008;10:1041–8.PubMedGoogle Scholar
  4. 4.
    Weber K, Osborn M, Moll R, Wiklund B, Luning B. Tissue polypeptide antigene (TPA) is related to the non-epidermal keratins 8, 18 and 19 typical of simple and non-squamous epithelia: re-evaluation of a human tumor marker. EMBO J. 1984;3:2707–14.PubMedGoogle Scholar
  5. 5.
    Silen A, Wiklund B, Andersson EL, Nilsson S. A novel IRMA and ELISA for quantifying cytokeratin 8 and 18 fragments in the sera of healthy individuals and cancer patients. Scand J Clin Lab Invest. 1995;55:153–40.PubMedCrossRefGoogle Scholar
  6. 6.
    Barak V, Goike H, Panaretakis KW, Einarsson R. Clinical utility of cytokeratins as tumor markers. Clin Biochem. 2004;37:529–40.PubMedCrossRefGoogle Scholar
  7. 7.
    Greystoke A, Cummings J, Ward T, Simpson K, Renehan A, Butt F, et al. Optimisation of circulating biomarkers of cell death for routine clinical use. Ann Oncol. 2008;19:990–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Bilici A, Ustaalioglu BB, Ercan S, Seker M, Yilmaz BE, Orcun A, et al. The prognostic significance of the increase in the serum M30 and M65 values after chemotherapy and relationship between these values and clinicopathological factors in patients with advanced gastric cancer. Tumour Biol. 2012;33:2201–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Bilici A, Ustaalioglu BBO, Ercan S, Orcun A, Seker M, Salepci T, et al. Is there any impact of plasma M30 and M65 levels on progression-free survival of patients with advanced gastric cancer? Cancer Chemother Pharmacol. 2011;68:309–16.PubMedCrossRefGoogle Scholar
  10. 10.
    Yaman E, Coskun U, Sancak B, Buyukberber S, Ozturk B, Benekli M. Serum M30 levels are associated with survival in advanced gastric carcinoma patients. Int Immunopharmacol. 2010;10:719–22.PubMedCrossRefGoogle Scholar
  11. 11.
    Ausch C, Buxhofer-Ausch V, Olszewski U, Hinterberger W, Ogris E, Schiessel R, et al. Caspase-cleaved cytokeratin 18 fragment (M30) as marker of post operative residual tumor load in colon cancer patients. Eur J Surg Oncol. 2009;35:1164–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Ausch C, Buxhofer-Ausch V, Olszewski U, Schiessel R, Ogris E, Hinterberger W, et al. Circulating cytokeratin 18 fragment M65—a potential marker of malignancy in colorectal cancer patients. J Gastrointest Surg. 2009;13:2020–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Koelink PJ, Lamers CB, Hommes DW, Verspaget HW. Circulating cell death products predict clinical outcome of colorectal cancer patients. BMC Cancer. 2009;9:88.PubMedCrossRefGoogle Scholar
  14. 14.
    Brandt D, Volkmann X, Anstatt M, Langer F, Manns MP, Schulze-Osthoff K, et al. Serum biomarkers of cell death for monitoring therapy response of gastrointestinal carcinomas. Eur J Cancer. 2010;46:1464–73.PubMedCrossRefGoogle Scholar
  15. 15.
    Scott LC, Evans TRJ, Cassidy J, Harden S, Paul J, Ullah R, et al. Cytokeratin 18 in plasma of patients with gastrointestinal adenocarcinoma as a biomarker of tumour response. Br J Cancer. 2009;101:410–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Ueno T, Toi M, Biven K, Bando H, Ogawa T, Linder S. Measurement of an apoptotic product in the sera of breast cancer patients. Eur J Cancer. 2003;39:769–74.PubMedCrossRefGoogle Scholar
  17. 17.
    Olofsson MH, Ueno T, Pan Y, Xu R, Cai F, van der Kuip H, et al. Cytokeratin-18 is a useful serum biomarker for early determination of response of breast carcinomas to chemotherapy. Clin Cancer Res. 2007;13:3198–206.PubMedCrossRefGoogle Scholar
  18. 18.
    Demiray M, Ulukaya EE, Arslan M, Gokgoz S, Saraydaroglu O, Ercan I, et al. Response to neoadjuvant chemotherapy in breast cancer could be predictable by measuring a novel serum apoptosis product, caspase-cleaved cytokeratin 18: a prospective pilot study. Cancer Invest. 2006;24:669–76.PubMedCrossRefGoogle Scholar
  19. 19.
    Ulukaya E, Yilmaztepe A, Akgoz S, Linder S, Karadag M. The levels of caspase-cleaved cytokine 18 are elevated in serum from patients with lung cancer, helpful to predict the survival. Lung Cancer. 2007;56:399–404.PubMedCrossRefGoogle Scholar
  20. 20.
    Ustaalioglu BO, Bilici A, Ercan S, Orcun A, Seker M, Ozkan A, et al. Serum M30 and M65 values in patients with advanced stage non-small-cell lung cancer compared with controls. Clin Transl Oncol. 2012;14:356–61.PubMedCrossRefGoogle Scholar
  21. 21.
    Ozturk B, Coskun U, Sancak B, Yaman E, Buyukberber S, Benekli M. Elevated serum levels of M30, M65 in patients with locally advanced head, neck tumors. Int Immunopharmacol. 2009;9:645–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. CA Cancer J Clin. 2010;60:277–300.PubMedCrossRefGoogle Scholar
  23. 23.
    Dive C, Smith RA, Garner E, Ward T, George-Smith SS, Campbell F, et al. Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer. Br J Cancer. 2010;102:577–82.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Faruk Tas
    • 1
  • Senem Karabulut
    • 1
  • Elif Bilgin
    • 1
  • Fatma Sen
    • 1
  • Ibrahim Yildiz
    • 1
  • Didem Tastekin
    • 1
  • Rumeysa Ciftci
    • 1
  • Derya Duranyildiz
    • 1
  1. 1.Institute of OncologyUniversity of IstanbulCapaTurkey

Personalised recommendations