Clinical utility of anti-p53 auto-antibody: Systematic review and focus on colorectal cancer

Table 1 Cumulative reported frequencies of anti-p53 auto-antibody (anti-p53) in controls and individual cancers n (%)

Group	Ref.	Anti-p53 positive	Summary of study and tumour type
	Park et al[107]	4/79 (5)	Comparative study with lung cancer
Healthy/Benign	Wu et al[133]	9/879 (1)	Case-control study of anti-p53 in various cancers
	Kulić et al[134]	1/20 (5)	Comparative study with breast carcinoma
	Suppiah et al[130]	0/28 (0)	Comparative study with colorectal carcinoma
	Cai et al[125]	0/30 (0)	Comparative study with oesophageal carcinoma
	Atta et al[135]	5/29 (17.2); 13/26 (50)1	Comparative study with hepatocellular carcinoma
	Mattioni et al[136]	0/64 (0)	Comparative study with gastric carcinoma
	Akere et al[137]	4/45 (8.9)	Comparative study with hepatocellular carcinoma
	Müller et al[123]	0/57 (0); 0/379 (0)2	Single study of anti-p53 in various cancers
	Chang et al[85]	0/40 (0)	Comparative study with colorectal carcinoma
	Fonseca et al[95]	0/15 (0)	Comparative study with glioma
	Shimada et al[82]	10/205 (6.3); 13/189 (7)3	Multi-institutional study of anti-p53 in various cancers
	Neri et al[138]	0/51 (0)	Comparative study with lung carcinoma
	Numa et al[139]	0/9 (0)	Comparative study with uterine, ovarian, cervical carcinoma
	Mack et al[140]	1/46 (2.2)	Comparative study with SCLC
	Chow et al[141]	1/28 (3.6)	Comparative study with head and neck carcinoma
	Moch et al[142]	2/130 (1.5)	Comparative study with skin carcinoma (SCC/BCC)
	Hofele et al[143]	0/80 (0)	Comparative study with oral SCC
	Hagiwara et al[144]	0/13 (0)	Comparative study with oesophageal carcinoma
	Ralhan et al[145]	4/50 (8)	Comparative study with lung carcinoma
	Bielicki et al[111]	0/28 (0)	Comparative study with colorectal carcinoma
	Soussi[90]	35/2404 (1.5)	Literature review of anti-p53 in various cancers (1979-1999)
	Total	102/4924 (2.1)
	Blanchard et al[146]	24/97 (28)	Correlates with decreased overall and disease free survival
Oesophageal	Wu et al[133]	4/29 (13.8)	Case-control study of anti-p53 in various cancers
	Cai et al[125]	18/46 (39.1)	Correlates with advanced histological grade, stage, lymph node metastases and decreased tumour response following radiotherapy
	Müller et al[123]	10/50 (20)	No correlation with stage or prognosis
	Bergström et al[147]	31/42 (73.8)	No correlation with clinico-pathological parameters, tumour size or survival
	Shimada et al[82]	90/301 (29.9)	Multi-institutional study of anti-p53 in various cancers
	Kozłowski et al[148]	20/75 (26.6)	No correlation with stage, lymph node metastases or size.
	Shimada et al[99]	14/35 (40)	Correlates with tumour p53 protein expression but not clinico-pathological parameters
	Hagiwara et al[144]	13/46 (28)	Correlates with increased stage and tumour p53 protein expression but not prognosis
	Ralhan et al[145]	36/60 (60)	Correlates with tumour p53 protein expression and missense mutations but not clinico-pathological parameters.
	Soussi[90]	85/274 (31)	Literature review of anti-p53 in various cancers (1979-1999)
	Total	345/1055 (32.7)
Head/Neck16	Wu et al[133]	1/20 (5.0)	Case-control study of anti-p53 in various cancers
	Shimada et al[82]	10/31 (32.3)	Multi-institutional study of anti-p53 in various cancers
	Chow et al[141]	23/75 (31)	Correlates with nodal metastases but not prognosis
	Total	34/126 (27.0)
Oral	Wu et al[133]	5/15 (33.3)	Case-control study of anti-p53 in various cancers
	Hofele et al[143]	19/102 (18.6)4; 12/24 (50)5	Correlates with poor prognosis
	Castelli et al[149]	3/61 (18.7); 9/13 (69.2)3	Serum anti-p53 is useful as a screening tool in pre-malignant lesions
	Soussi[90]	309/1062 (29.1)	Literature review of anti-p53 in various cancers (1979-1999)
	Total	348/1219 (28.5)
Ovary	Wu et al[133]	5/12 (41.6)	Case-control study of anti-p53 in various cancers
	Qiu et al[150]	36/92 (39.1)	Correlates with p53 expression, not clinico-pathological parameters
	Shimada et al[82]	2/27 (7.4)	Multi-institutional study of anti-p53 in various cancers
	Numa et al[139]	8/30 (27)	Correlates with p53 tumour expression and poor prognosis
	Abendstein et al[151]	28/113 (25); 21/113 (19)6	Correlation between serum and ascitic anti-p53. No correlation with stage or grade. Anti-p53 in ascites associated with poor prognosis
	Soussi[90]	140/635 (22)	Literature review of anti-p53 in various cancers (1979-1999)
	Total	219/909 (24.1)
Colorectal(detailed results in Table 2)	Wu et al[133]	11/66 (16.7)	Case-control study of anti-p53 in various cancers
	Suppiah et al[130]	20/92 (21.7)	No correlation with stage or prognosis
	Nozoe et al[97]	17/36 (47.2)	Correlates with advanced lymph node status and stage
	Müller et al[123]	63/197 (32)7; 7/46 (15.2)8	No correlation with stage or prognosis
	Chang et al[85]	47/167 (28.1)	p53 mutation, not anti-p53, correlates with poor prognosis
	Lechpammer et al[88]	40/220 (18.2)	? Correlation with stage or prognosis in Dukes’ A/B1
	Shimada et al[82]	46/192 (23.9)	Multi-institutional study of anti-p53 in various cancers
	Forslund et al[84]	24/88 (27.3)	Correlates with p53 mutation
	Tang et al[89]	130/998 (13)	Correlates with advanced lymph node involvement but not prognosis
	Broll et al[152]	20/130 (15.4)	No correlation with stage or prognosis
	Takeda et al[98]	17/27 (63)	95% negative sero-conversion within 3 wk post-surgery
	Shiota et al[112]	18/71 (25.4)	Correlates with advanced stage and poor prognosis
	Bielicki et al[111]	30/145 (20.7)	? Correlation with Dukes’ A →B
	Soussi[90]	307/1244 (24.7)	Literature review of anti-p53 in various cancers (1979-1999)
	Total	797/3719 (21.4)
HCC	Wu et al[133]	15/93 (16.1)	Case-control study of anti-p53 in various cancers
	Atta et al[135]	28/41 (68.3)	Correlates with advanced stage and shorter survival.
	Akere et al[137]	5/41 (12.2)	Correlates with increased Okuda stage
	Müller et al[123]	19/80 (23.8)	Non-significant trend towards poor prognosis
	Charuruks et al[153]	26/141 (18.4)	Correlates with stage but not tumour p53 protein expression
	Tangkijvanich et al[154]	16/121 (13.2)17	Preliminary report of Charuruks et al (2001). No correlation with severity, stage or prognosis. Survival too short for survival analysis (3 mo vs 4 mo)
	Sitruk et al[155]	19/159 (12)	Correlates with multinodular, infiltrative tumour but not survival
	Soussi[90]	82/387 (1.2)	Literature review of anti-p53 in various cancers (1979-1999)
	Total	210/1063 (19.8)
	Wu et al[133]	0/11 (0)	Case-control study of anti-p53 in various cancers
Bladder	Müller et al[123]	3/24 (12.5)	No correlation with prognosis
	Watanabe et al[156]	17/63 (27)9	Correlates with higher grade, stage, lymph node metastases and tumour p53 protein expression, but not prognosis
	Gumus et al[157]	14/80 (17.5)	Correlates with tumour p53 protein expression and poor prognosis.
	Gumus et al[158]	25/76 (33)	Negative sero-conversion post-treatment (35%, 8/23) associated with good prognosis.
	Shimada et al[82]	4/33 (12.1)	Multi-institutional study of anti-p53 in various cancers
	Morita et al[159]	12/100 (12)	Correlates with stage, and p53 protein expression but not prognosis
	Wunderlich et al[160]	4/32 (12.5)	Correlates with tumour protein p53 expression but not stage.
	Soussi[90]	8/29 (27.6)	Literature review of anti-p53 in various cancers (1979-1999)
	Total	70/385 (18.2)
Lung	Park et al[107]	28/82 (34.1)	Sensitivity study with other markers for lung cancer
	Wu et al[133]	13/95 (13.7)	Case-control study of anti-p53 in various cancers
	Bergqvist et al[161]	14/84 (16.6)	No correlation with tumour volume. Correlates with survival in adenocarcinoma, but not SCC
	Bergqvist et al[162]	12/58 (20.7)	No correlation with tumour volume or lymph node metastases
	Neri et al[138]	2/30 (6.7)10; 8/48(16.7)11	No correlation with stage, histology or prognosis. Non-significant increased survival in LC but not MM
	Cioffi et al[163]	35/109 (32.1)	Low sensitivity, but high specificity (100%) and accuracy (69%). Only 14% agreement with other tumour markers (CEA/TPA, CYFRA21-1, NSE.)
	Zalcman et al[126]	20/97 (20.6)	Correlates with poor prognosis in limited stage SCLC, but not all SCLC
	Mack et al[140]	4/35 (11.1)12; NSCLC 13/99 (13.3)13	Correlates with stage and prognosis in NSCLC but not SCLC
	Shimada et al[82]	18/125 (14.4)	Multi-institutional study of anti-p53 in various cancers
	Soussi[90]	219/1282 (17.1)	Literature review of anti-p53 in various cancers (1979-1999)
	Total	373/2049 (18.2)
Cervix	Shimada et al[82]	10/53 (18.9)	Multi-institutional study of anti-p53 in various cancers
	Numa et al[139]	12/86 (14)	No correlation with tumour p53 protein expression or prognosis
	Total	22/139 (15.8)
	Wu et al[133]	7/43 (16.3)	Case-control study of anti-p53 in various cancers
Gastric	Qiu et al[150]	19/61 (31.1)	Correlates with tumour size but not prognosis.
	Mattioni et al[136]	17/111 (15.3)	Correlates with tumour p53 protein expression, prognosis and survival
	Lawniczak et al[164]	16/71 (22.5)	Correlates with tumour type and age, but not stage or prognosis
	Müller et al[123]	14/122 (11.5)	No correlation with prognosis
	Shimada et al[82]	13/123 (10.6)	Multi-institutional study of anti-p53 in various cancers
	Nakajima et al[165]	13/81 (16)	Correlates with lymph node metastases but not stage or prognosis
	Maehara et al[166]	23/120 (19.2)	Correlates with increased stage and tumour p53 protein expression but not prognosis
	Soussi et al[90]	105/727 (14.1)	Literature review of anti-p53 in various cancers (1979-1999)
	Total	227/1459 (15.6)
	Nozoe et al[167]	15/42 (35)	Correlates with grade 3 and triple negative cancer
Breast	Wu et al[133]	9/25 (16)	Case-control study of anti-p53 in various cancers
	Kulić et al[134]	21/61 (35)	Correlates with decreased 5 year survival
	Müller et al[123]	17/50 (34)	Non-significant trend towards poor prognosis
	Gao et al[168]	31/144 (21.5)	Correlates with stage, lymph node metastases, ER negative, c-erb-2 and tumour p53 protein expression
	Shimada et al[82]	13/71 (18.3)	Multi-institutional study of anti-p53 in various cancers
	Volkmann et al[169]	18/165 (10.9)	Poor concordance between recombinant/native p53 ELISA, immunoblot and immunofluorescence
	Metcalfe et al[87]	155/1006 (15.4)	No correlation with stage and prognosis
	Soussi[90]	296/2006 (14.8)	Literature review of anti-p53 in various cancers (1979-1999)
	Total	539/3467 (15.5)
Uterus	Wu et al[133]	1/13 (7.7)	Case-control study of anti-p53 in various cancers
	Shimada et al[82]	5/22 (22.7)	Multi-institutional study of anti-p53 in various cancers
	Numa et al[139]	5/41 (12)	No correlation with tumour p53 expression/prognosis (see Cervix, Ovary)
	Total	11/79 (13.9)
Pancreas	Wu et al[133]	0/17 (0)	Case-control study of anti-p53 in various cancers
	Müller et al[123]	5/22 (22.7)	Increase sensitivity in conjunction with CA19-9. No correlation with prognosis.
	Shimada et al[82]	3/28 (10.7)	Multi-institutional study of anti-p53 in various cancers
	Ohshio et al[170]	19/82 (23.2)	No correlation with tumour p53 expression or prognosis
	Soussi[90]	60/650 (9.2)	Literature review of anti-p53 in various cancers (1979-1999)
	Total	87/799 (10.9)
Lymphoma	Messmer et al[171]	19/120 (15.8)	Associated with 17p deletions
	Wu et al[133]	0/18 (0)	Literature review of anti-p53 in various cancers (1979-1999)
	Soussi[90]	19/248 (14.3)	Case-control study of anti-p53 in various cancers
	Total	38/386 (9.8)
Biliary tract16	Wu et al[133]	1/8 (6.3)	Correlates with tumour p53 protein expression but not stage
	Limpaiboon et al[172]	6/49 (12.2)	Multi-institutional study of anti-p53 in various cancers
	Shimada et al[82]	1/6 (16.7)	Correlates with tumour p53 mutation
	Tangkijvanich et al[173]	6/82 (7.3)
	Total	14/145 (9.7)
Haematological	Wu et al[133]	8/33 (25)	Case-control study of anti-p53 in various cancers
	Shimada et al[82]	32/364 (6.3)14	Multi-institutional study of anti-p53 in various cancers
	Soussi[90]	14/428 (3.3)15	Literature review of anti-p53 in various cancers (1979-1999)
	Total	54/825 (6.5)
Glioma	Wu et al[133]	1/24 (4.2)	Case-control study of anti-p53 in various cancers
	Fonseca et al[95]	5/24 (20.8)	No correlation with p53 protein but increased in patients < 16 years
	Shimada et al[82]	2/31 (6.5)	Multi-institutional study of anti-p53 in various cancers
	Soussi[90]	6/144 (4.2)	Literature review of anti-p53 in various cancers (1979-1999)
	Total	14/223 (6.3)
Prostate	Wu et al[133]	1/8 (12.5)	Case-control study of anti-p53 in various cancers
	Shimada et al[82]	4/23 (17.4)	Multi-institutional study of anti-p53 in various cancers
	Soussi[90]	4/148 (2.7)	Literature review of anti-p53 in various cancers (1979-1999)
	Total	9/179 (5.0)
Skin	Moch et al[142]	3/105 (2.9)	No difference between controls and patients. Increased in aggressive SCC (8%) vs slow-growing BCC (1.5%)
Testicular	Soussi[90]	0/144 (0)	Literature review of anti-p53 in various cancers (1979-1999)
Melanoma	Soussi[90]	0/58 (0)	Literature review of anti-p53 in various cancers (1979-1999)
Total		3419/18595 (18.4)	All cancers (1979-2012)

Cancer types are listed in order of decreasing anti-p53 auto-antibody frequency. The reported studies within each cancer type are listed in reverse chronology. Squamous cell carcinoma (SCC); basal cell carcinoma (BCC), hepatocellular carcinoma (HCC), carcino-embryonic antigen (CEA). Tissue polypeptide antigen (TPA), CYFRA21-1, Neurone-specific enolase (NSE), Oestrogen receptor (ER), c-erb-2.

¹Cirrhosis;

²Benign disease;

³Oral pre-malignant lesions-excluded from calculation;

⁴Primary carcinoma;

⁵Secondary/recurrent carcinoma;

⁶Ascitic titre, not included in calculation of serum titres;

⁷Colon;

⁸Rectum;

⁹Upper renal tract tumours, excluded from anti-p53 titres in bladder carcinoma;

¹⁰Malignant mesothelioma (MM);

¹¹Lung carcinoma (LC);

¹²Small cell lung carcinoma (SCLC);

¹³Non-small cell lung carcinoma (NSCLC);

¹⁴Myeloma;

¹⁵Leukaemia;

¹⁶Tumour type not specified;

¹⁷Excluded as is preliminary report of the same cohort (duplicate) reported in Charuruks et al.