Faecal pyruvate kinase isoenzyme type M2 for colorectal cancer screening: A meta-analysis

Table 1 Results of the literature search

Results	Reference
All papers dealing with faecal M2-PK found in a literature search of Pubmed and Embase	[7, 8, 10,18, 20-49]
Additional published studies known to the authors	[50-53]
Excluded papers - reasons for exclusion
Unique combination of antibodies	[47]
Reviews	[18, 24, 26, 28, 34, 38, 42]
Author replies or comments	[27, 32, 40]
Paper in Bulgarian language	[29]
No sensitivities or specificities calculated	[21, 48]
Studies referred to IBD	[20, 22, 23, 25, 36, 39, 43]
Included papers
Studies found in Pubmed and Embase	[7, 8, 10, 30, 31, 33, 35, 37, 41, 44-46, 49]
Published studies known to the authors	[50-53]

IBD: Inflammatory bowel diseases; faecal M2-PK: Faecal pyruvate kinase isoenzyme type M2

Table 2 Overview of included studies

Reference	Country of study	Conflict of interest regarding faecal M2-PK
Shastri et al[7], 2006	Germany	None declared
Koss et al[8], 2008	United Kingdom	None declared
Möslein et al[10], 2010	Germany	None declared
Haug et al[30], 2008	Germany	None declared
Shastri et al[31], 2008	Germany	Coauthor Stein: Conference speaker for ScheBo Biotech AG
Haug et al[33], 2007	Germany	None declared
Mulder et al[35], 2007	The Netherlands	None declared
Ewald et al[37], 2007	Germany	None declared
Tonus et al[41], 2006	Germany	Non declared
Vogel et al[44], 2005	Germany	Tests performed by ScheBo Biotech AG
Naumann et al[45], 2004	Germany	None declared
Hardt et al[46], 2004	Germany	None declared
Tonus et al[49], 2009	Germany	None declared
Kloer et al[50], 2005	Germany	None declared
McLoughlin et al[51], 2005	Ireland	None declared
Bellutti et al[52], 2005	Germany	None declared
Schmidt et al[53], 2009	Germany	None declared

Faecal M2-PK: Faecal pyruvate kinase isoenzyme type M2.

Table 3 Published sensitivities of the faecal pyruvate kinase isoenzyme type M2 test for colorectal cancer

Reference	n (%)
Hardt et al[46], 2004	60 (73)
Naumann et al[45], 2004	27 (85.2)
Kloer et al[50], 2005	147 (79.6)
McLoughlin et al[51], 2005	35 (97)
Vogel et al[44], 2005	22 (77)
Shastri et al[7], 2006	74 (81.1)
Tonus et al[41], 2006	54 (78)
Haug et al[33], 2007	65 (68)
Mulder et al[35], 2007	52 (85)
Koss et al[8], 2008	32 (81)
Shastri et al[31], 2008	55 (78.2)
Schmidt et al[53], 2009	81 (80.3)
Sum	704
mean ± SD	80.3 ± 7.1

n: Number of colorectal cancer samples; %: Sensitivity.

Table 4 Correlation of faecal pyruvate kinase isoenzyme type M2 sensitivity with tumor node metastasis and Dukes classification n (%)

Reference	Tumor node metastasis classificatoin				Dukes classification
	T1	T2	T3	T4	Dukes A	Dukes B	Dukes C	Dukes D
Kloer et al[50], 2005	9 (55.5)	18 (61.1)	49 (81.6)	12 (83.3)	23 (52.2)	24 (76.0)	26 (80.8)	17 (82.4)
Tonus et al[41], 2006	5 (60)	11 (64)	25 (89)	4 (100)	5 (60.0)	17 (76.0)	9 (89)	10 (90.0)
Haug et al[33], 2007	6 (67)	16 (44)	34 (71)	4 (100)	12 (67.0)	18 (61.0)	12 (67.0)	6 (100.0)
Schmidt et al[53], 2009	8 (57)	20 (84)	42 (79)	11 (91)
Hardt et al[46], 2004	7 (57)	11 (64)	33 (78)	9 (78)
Sum	35	76	183	40	40	59	47	33
mean ± SD	59 ± 5	63 ± 14	80 ± 7	90 ± 10	60 ± 7	71 ± 9	79 ± 11	91 ± 9

n: Number of samples tested; %: Sensitivity.

Table 5 Head-to-head comparison of the sensitivity for colorectal cancer of faecal pyruvate kinase isoenzyme type M2 and guaiac-based faecal occult blood test n (%)

Reference	CRC M2-PK	CRC gFOBT
Naumann et al[45], 2004	27 (85.2)	27 (62.9)
Vogel et al[44], 2005	22 (77)	22 (27)
Shastri et al[7], 2006	74 (81.1)	74 (36.5)
Koss et al[8], 2008	32 (81)	32 (21)
Sum	155	155
mean ± SD	81.1 ± 3.3	36.9 ± 18.5

n: Number of samples tested; %: Sensitivity; CRC: Colorectal cancer; gFOBT: Guaiac-based faecal occult blood test; M2-PK: Pyruvate kinase isoenzyme type M2.

Table 6 Sensitivity of faecal pyruvate kinase isoenzyme type M2 for adenoma n (%)

Reference	Adenoma without diameter	Adenoma < 1 cmø	Adenoma > 1 cmø
Naumann et al[45], 2004		11 (27.3)	13 (61.5)
McLoughlin et al[51], 2005	30 (76)
Vogel et al[44], 2005	21 (48)
Shastri et al[7], 2006		21 (28.6)	10 (20.0)
Mulder et al[35], 2007	47 (28)
Koss et al[8], 2008		5 (20)	5 (60)
Shastri et al[31], 2008		48 (29.2)	21 (57.1)
Haug et al[30], 2008		254 (22.1)	68 (23.5)
Sum	98	339	117
mean ± SD	51 ± 24	25 ± 4	44 ± 21

n: Number of samples tested; %: Sensitivity;ø: Diameter.

Table 7 Head-to-head comparison of sensitivity for adenoma of faecal pyruvate kinase isoenzyme type M2 and guaiac-based faecal occult blood test n (%)

Reference	Adenoma < 1 cmøM2-PK	Adenoma < 1 cmøgFOBT	Adenoma > 1 cmøM2-PK	Adenoma > 1 cmøgFOBT	Adenoma w/oøM2-PK	Adenoma w/oøgFOBT
Naumann et al[45], 2004	11 (27.3)	11 (18.2)	13 (61.5)	13 (30.8)
Vogel et al[44], 2005					21 (48)	21 (9)
Shastri et al[7], 2006	21 (28.6)	21 (9.5)	10 (20.0)	10 (30.0)
Koss et al[8], 2008	5 (20.0)	5 (0.0)	5 (60.0)	5 (20.0)
Sum	37	37	28	28	21	21
mean ± SD	25 ± 5	9 ± 9	47 ± 24	27 ± 6

n: Number of samples tested; %: Sensitivity; w/o ø: Without measurement of diameter; ø: Diameter; gFOBT: Guaiac-based faecal occult blood test; M2-PK: Pyruvate kinase isoenzyme type M2.

Table 8 Measurements of faecal pyruvate kinase isoenzyme type M2 in stool samples of healthy individuals

Reference	No. of healthy participants	Test-negative participants (%)	Colonoscopy (yes/no)	Specificity (%)
Belluti et al[52], 2005	2787	91.6	No	97.4 (e)
McLoughlin et al[51], 2005	97	98	Yes	98
Tonus et al[41], 2006	42	93	Yes	93
Ewald et al[37], 2007	1906	90.4	No
Haug et al[33], 2007	917	78.6	No
Koss et al[8], 2008	13	100.0	Yes	100.0
Tonus et al[49], 2009	4854	91.2	No	93.4 (e)
Möslein et al[10], 2010	796	89.5	Yes	89.5
Sum	11 412
mean ± SD		91.5 ± 6.4		95.2 ± 3.9

e: Estimated specificities calculated by authors based on the sensitivity of faecal pyruvate kinase isoenzyme type M2 for colorectal cancer (CRC) and advanced neoplasia, and the prevalence of CRC and advanced adenoma.