Tumour M2-PK as a stool marker for colorectal cancer: comparative analysis in a large sample of unselected older adults vs colorectal cancer patients

Abstract

Stool testing based on tumour-derived markers might offer a promising approach for non-invasive colorectal cancer (CRC) screening. The aim of this study was to estimate the potential of a new test for faecal tumour M2-PK to discriminate patients with CRC from a large sample of unselected older adults. Faecal tumour M2-PK concentrations were determined in 65 CRC patients and in a population-based sample of 917 older adults (median age: 65 and 62 years, respectively). Sensitivity and specificity of the test were calculated at different cutoff values, and receiver-operating characteristic curves (ROC) were constructed to visualise the discriminatory power of the test. The median (interquartile range) faecal tumour M2-PK concentration was 8.6 U ml À1 (2.8 -18.0) among CRC patients and o2 U ml À1 (o2 -3.2; Po0.0001) in the population sample. At a cutoff value of 4 U ml À1 , sensitivity (95% confidence interval) was 85% (65 -96%) for colon cancer and 56% (41 -74%) for rectum cancer. Specificity (95% confidence interval) was estimated to be 79% (76 -81%). Given the comparatively high sensitivity of the tumour M2-PK stool test (especially for colon cancer) and its simple analysis, the potential use of the test for early detection of CRC merits further investigation. Possibilities to enhance specificity of the test should be explored. Colorectal cancer (CRC) is one of the leading causes of cancerrelated morbidity and mortality worldwide (Ferlay et al, 2004). Even in countries where up-to-date therapeutic options are available, more than 40% of CRC patients still die from the disease within 5 years after diagnosis (Brenner, 2002;Brenner et al, 2005). As survival is considerably better for early, localised CRC than for later stages and CRC might be prevented altogether by detection and removal of precancerous lesions, enhanced screening will be of crucial importance for further progress in reducing the burden of the disease.Experience with faecal occult blood testing (FOBT) has shown the possibility of reducing both incidence and mortality owing to screening based on stool tests (Hardcastle et al, 1996;Mandel et al, 1999Mandel et al, , 2000 and the advantages of this screening modality regarding acceptability and practicality compared with invasive screening options. However, given the limitations of FOBT, mainly the inherently low sensitivity to detect precancerous or cancerous lesions, there is still need for improvement. Therefore, the development of stool tests with better performance characteristics has become a focus of current research, both in the field of DNAbased stool markers and in the field of protein-based stool markers. For some of the new tests, preliminary results regarding sensitivity and specificity are encouraging but evidence of the performance of the new methods is mostly restricted to small-scale investigations in the clinical setting (Haug and Brenner, 2005a).A novel approach based on the detection of proteins in stool derived from neoplastic colonocytes is the quantitative measurement of faecal tum...

New faecal tests for colorectal cancer screening: is tumour pyruvate kinase M2 one of the options?

“…Thus, assuming that a sensitivity of around 35% for diagnosing these advanced adenomas from the above two studies would be applied to the population studied, then there would be a marked decrease in the resulting sensitivity of M2-PK for diagnosing colorectal neoplasia (CRN), that is CRC with advanced adenomas. Thus, the estimated sensitivity of M2-PK in diagnosing CRN would decrease to 48% (26 þ 45/73 þ 74) as against 67% (45/74) reported in this study (Haug et al, 2007). This would be highly unacceptable for any CRC screening test and especially for M2-PK with such a poor specificity of around 80%, which is much lower than that of any of the faecal screening tests for CRC, in fact even lower than that of Guaiac-based faecal occult blood test (FOBTs).…”

“…The ability of various CRC screening programme (eg, colonoscopy) in reducing CRC mortality by diagnosing and removing these premalignant lesions cannot be overemphasised. It is agreed that the false positives due to these adenomas in the control group would have contributed to marginal increase in the specificity of faecal pyruvate kinase type M2 (M2-PK) in their study (Haug et al, 2007), as rightly mentioned by the authors.…”

“…The ability of various CRC screening programme (eg, colonoscopy) in reducing CRC mortality by diagnosing and removing these premalignant lesions cannot be overemphasised. It is agreed that the false positives due to these adenomas in the control group would have contributed to marginal increase in the specificity of faecal pyruvate kinase type M2 (M2-PK) in their study (Haug et al, 2007), as rightly mentioned by the authors.But what about the adenomas that could have been missed out by performing M2-PK assay in the controls? The prevalence of any adenomatous lesion in their control group would have been somewhere around 30% and roughly 8% would have been advanced adenomas (Anderson et al, 2003), usually described as villous adenomas, tubular adenomas 410 mm, high-grade dysplasia, malignant polyp or 43 adenomas (ie, around 73 out of these 917 control group patients (Haug et al, 2007)).…”

“…It is agreed that the false positives due to these adenomas in the control group would have contributed to marginal increase in the specificity of faecal pyruvate kinase type M2 (M2-PK) in their study (Haug et al, 2007), as rightly mentioned by the authors.…”

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Cancer Research UK

Sir,We read with great interest the article by Haug et al (2007) and must complement them for a nicely written work. We have certain comments to make about their study.

Colorectal adenomas, the precursors of almost all of the sporadic colorectal cancer (CRC) could not be included in their study.

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