M2-PK as a novel marker in ovarian cancer. A prospective cohort study

Background: Pyruvate kinase isoenzyme M2-PK is instrumental to tumour metabolism and hence over-expressed in tumour cells leading to detectable plasma concentrations.

Objectives: To assess the degree of association between M2-PK plasma concentrations and ovarian cancer and to determine the cut-off values for its sensitivity and specificity for differentiating between benign and malignant ovarian disease.

Settings: The Gynaecological Cancer Centre at both King's College and St. Thomas' Hospitals, London, UK.

Methods: Patients with suspected ovarian cancer referred to the above centre were recruited prospectively during the years 2004-2005. Blood samples were collected before surgery for plasma M2-PK assays. Results were assessed with respect to cancer diagnosis, patient and tumour characteristics. Statistical analysis including the receiver operator characteristic (ROC) curve was performed using Analyse-It and SPSS V 13.

Results: 100 patients with age range 14-88 years and a median of 57 years were recruited in the study. Of whom 52 were diagnosed with invasive ovarian cancer. Of these 35 (67%) were Stage III and above with two secondary tumours. M2-PK was not related to patient age (p = 0.43). There was a significant correlation between CA125 and M2-PK (p < 0.001). The mean M2-PK concentration in cancer patients was 52 U/ml versus 27 U/ml in patients with benign conditions (p < 0.001). At a cut-off value of 22 U/ml the sensitivity of M2-PK for detecting cancer was 70% with a specificity of 65%.

Conclusion: M2-PK was significantly raised in ovarian cancer patients, however its role in clinical practice needs further evaluation.

Ovarian cancer; Pyruvate Kinase; M2-PK; Tumour Marker, Diagnosis

[1] Parkin D.M., Bray F., Ferlay J., Pisani P.: "Global cancer statistics, 2002". CA Cancer J. Clin., 2005, 55, 74.

[2] Jemal A., Tiwari R.C., Murray T., Ghafoor A., Samuels A., Ward E. et al.: "American Cancer Society. Cancer statistics, 2004". CA Cancer J. Clin., 2004, 54, 8, Review

[3] Cancer Research UK: "Ovarian Cancer-UK". CancerStats report, February, 2004.

[4] Heintz A.P., Odicino F., Maisonneuve P., Beller U., Benedet J.L., Creasman W.T. et al.: "Carcinoma of the ovary". J. EpidemiolBiostat., 2001, 6, 107.

[5] International Federation of Gynecology and Obstetrics: "Annual Report on the Results of Treatment in Gynecological". Cancer, 1998, 23.

[6] Menon U., Jacobs I.: "Screening for ovarian cancer". Best. Pract. Res. Clin. Obstet. Gynaecol., 2002, 16, 469.

[7] Ahmed A.S., Long M., Donaldson D.: "Ascites and elevated serum CA 125 due to a pancreatic carcinoma; A diagnostic dilemma". J R. Soc. Health., 2000, 120, 268.

[8] NIH consensus conference: "Ovarian cancer. Screening, treatment, and follow-up. NIH Consensus Development Panel on Ovarian Cancer". JAMA, 1995, 273, 491.

[9] Vaupel P., Kallinowski F., Okunieff P.: "Blood flow, oxygen con­sumption and tissue oxygenation of human tumors". Adv. Exp Med. Biol., 1990, 277, 895.

[10] Eigenbrodt E., Kallinowski F., Ott M., Mazurek S., Vaupel P "Pyruvate kinase and the interaction of amino acid and carbohy­drate metabolism in solid tumors". Anticancer Res., 1998, 18, 3267.

[11] Mazurek S., Grimm H., Boschek C.B., Vaupel P., Eigenbrodt E. "Pyruvate kinase type M2: a crossroad in the tumor metabolome". Br. J. Nutr., 2002, 87 (suppl. 1), S23.

[12] Mazurek S., Boschek C., Hugo F., Eigenbrodt E.: "Pyruvate kinase type M2 and its role in tumor growth and spreading". Semin Cancer Biol., 2005, 15, 300.

[13] Schneider J., Neu K., Grimm H., Velcovsky H.G., Weisse G., Eigenbrodt E.: "Tumor M2- pyruvate kinase in lung cancer patients: immunohistochemical detection and disease monitoring" Anticancer Res., 2002, 22, 311.

[14] Hugo F., Fischer G., Eigenbrodt E.: "Quantitative detection of tumor M2-PK in serum and plasma". Anticancer Res., 1999, 19, 2753.

[15] Davies A.P., Jacobs I., Woolas R., Fish A., Oram D.:'The adnexal mass: benign or malignant? Evaluation of a risk of malignancy index". Br. J. Obstet. Gynaecol., 1993, JOO, 927

[16] International Federation of Gynecology and Obstetrics: "Changes in definitions of clinical staging for carcinoma of the cervix and ovary". Am. J. Obstet. Gynecol., 1987, 156, 263.

[17] Serov S.F., Scully R.E., Sobin L.H.: "Histological typing of ovarian tumours". International Histological Classification of Tumours, No. 9, World Health Organization, Geneva, 1973.

[18] Benda J.A., Zaino R.: "GOG Pathology Manual". Buffalo, Gyne­cologic Oncology Group, 1994.

[19] Glas A.S., Lijmer J.G., Prins M.H., Bonsel G.J., Bossuyt P.M "The diagnostic odds ratio: a single indicator of test performance"J. Clin. Epidemiol., 2003, 56, 1129.

[20] Schulze G.:'The tumor marker tumor M2-PK: an application m the diagnosis of gastrointestinal cancer". Anticancer Res., 2000, 20, 4961.

[21] Roigas J., Schulze G., Raytarowski S 呵 Jung K., Schnorr D., Loening S.A.: "Tumor M2 pyruvate kinase in plasma of patients with urological tumors". Tumour Biol., 2001, 22, 282.

[22] Ventrucci M., Cipolla A., Racchini C., Casadei R., Simoni P., Gullo L.:'Tumor M2-pyruvate kinase, a new metabolic marker for pancreatic cancer". Dig. Dis. Sci., 2004, 49, 1149.

[23] Bena-Boupda N.F., Re瓜i S.S., Klett R., Eigenbrodt E., Bauer R "Value of tumor M2-PK in thyroid carcinoma: a pilot study". Anti­cancer Res., 2003, 23, 5237.

[24] Ugurel S., Bell N., Sucker A., Zimpfer A., Rittgen W., Schaden­dorf D.: "Tumor type M2 pyruvate kinase (TuM2-PK) as a novel plasma tumor marker in melanoma". Int. J. Cancer., 2005, I 17, 825.

[25] Kaura B., Bagga R., Patel F.D.: "Evaluation of the Pyruvate Kinase isoenzyme tumor (Tu M2-PK) as a tumor marker for cer­vical carcinoma". J. Obstet. Gynaecol. Res,. 2004, 30, 193.

[26] Staib P., Hoffmann M., Schinkothe T.: "Plasma levels of tumor M2-pyruvate kinase should not be used as a tumor marker for hematological malignancies and solid tumors". Clin. Chem. Lab. Med., 2006, 44, 28.

[27] Sevinc A., Sari R., Camci C., Buyukberber S.: "A secondary inter­pretation is needed on serum CA125 levels in case of serosal involvement". J. R. Soc. Health., 2000, 120, 268.

[28] Sevinc A., Camci C., Turk H.M., Buyukberber S.: "How to inter­pret serum CA 125 levels in patients with serosal involvement? A clinical dilemma". Oncology, 2003, 65, 1.