Introduction: Anti-p53 antibody (p53Ab) is useful for monitoring colorectal cancer (CRC) recurrence. We retrospectively analyzed the clinical impact of p53Ab ratio (p53R) before and after surgery to predict recurrence in patients with CRC. Methods: In total, 1,223 patients with stage I–III CRC who underwent curative surgery between January 2005 and December 2019 were enrolled in this retrospective study. In patients with elevated p53Ab levels, p53R was calculated by measuring p53Ab levels within 1 month preoperatively and 3 months postoperatively. The optimal p53R level was determined, and its relationship with clinicopathological factors and prognosis was examined. We also evaluated the efficacy of the combination of p53R and preoperative carcinoembryonic antigen (CEA) values. Results: Overall, 341 patients (27.9%) showed elevated p53Ab levels. Preoperative p53Ab levels were significantly associated with tumor location, lymphatic invasion, and venous invasion. The p53R level was significantly higher in patients with recurrent disease. Patients with high p53R levels had significantly shorter relapse-free survival than those with low p53R levels (p < 0.001). When p53R was combined with preoperative CEA values, specificity improved to 0.97, with an accuracy of 0.88. Conclusion: In patients with CRC and elevated preoperative p53Ab levels, p53R expression may be prognostically useful after radical resection. Furthermore, the combination of p53R and preoperative CEA levels may be useful for postoperative follow-ups.

1.
Sung
H
,
Ferlay
J
,
Siegel
RL
,
Laversanne
M
,
Soerjomataram
I
,
Jemal
A
, et al
.
Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries
.
CA Cancer J Clin
.
2021
;
71
(
3
):
209
49
. .
2.
Van Cutsem
E
,
Nordlinger
B
,
Adam
R
,
Kohne
CH
,
Pozzo
C
,
Poston
G
, et al
.
Towards a pan-European consensus on the treatment of patients with colorectal liver metastases
.
Eur J Cancer
.
2006
;
42
(
14
):
2212
21
. .
3.
Nigro
JM
,
Baker
SJ
,
Preisinger
AC
,
Jessup
JM
,
Hostetter
R
,
Cleary
K
, et al
.
Mutations in the p53 gene occur in diverse human tumour types
.
Nature
.
1989
;
342
(
6250
):
705
8
. .
4.
Hollstein
M
,
Sidransky
D
,
Vogelstein
B
,
Harris
CC
.
p53 mutations in human cancers
.
Science
.
1991
;
253
(
5015
):
49
53
. .
5.
Abe
S
,
Kawai
K
,
Ishihara
S
,
Nozawa
H
,
Hata
K
,
Kiyomatsu
T
, et al
.
Prognostic value of pre- and postoperative anti-p53 antibody levels in colorectal cancer patients: a retrospective study
.
Oncology
.
2017
;
92
(
1
):
31
8
. .
6.
Suppiah
A
,
Alabi
A
,
Madden
L
,
Hartley
JE
,
Monson
JR
,
Greenman
J
.
Anti-p53 autoantibody in colorectal cancer: prognostic significance in long-term follow-up
.
Int J Colorectal Dis
.
2008
;
23
(
6
):
595
600
. .
7.
Houbiers
JG
,
van der Burg
SH
,
van de Watering
LM
,
Tollenaar
RA
,
Brand
A
,
van de Velde
CJ
, et al
.
Antibodies against p53 are associated with poor prognosis of colorectal cancer
.
Br J Cancer
.
1995
;
72
(
3
):
637
41
. .
8.
Shiota
G
,
Ishida
M
,
Noguchi
N
,
Oyama
K
,
Takano
Y
,
Okubo
M
, et al
.
Circulating p53 antibody in patients with colorectal cancer: relation to clinicopathologic features and survival
.
Dig Dis Sci
.
2000
;
45
(
1
):
122
8
. .
9.
Ochiai
H
,
Ohishi
T
,
Osumi
K
,
Tokuyama
J
,
Urakami
H
,
Seki
S
, et al
.
Reevaluation of serum p53 antibody as a tumor marker in colorectal cancer patients
.
Surg Today
.
2012
;
42
(
2
):
164
8
. .
10.
Wang
J
,
Wang
X
,
Yu
F
,
Chen
J
,
Zhao
S
,
Zhang
D
, et al
.
Combined detection of preoperative serum CEA, CA19-9 and CA242 improve prognostic prediction of surgically treated colorectal cancer patients
.
Int J Clin Exp Pathol
.
2015
;
8
(
11
):
14853
63
.
11.
Jia
J
,
Zhang
P
,
Gou
M
,
Yang
F
,
Qian
N
,
Dai
G
.
The role of serum CEA and CA19-9 in efficacy evaluations and progression-free survival predictions for patients treated with cetuximab combined with FOLFOX4 or FOLFIRI as a first-line treatment for advanced colorectal cancer
.
Dis Markers
.
2019
;
2019
:
6812045
. .
12.
Brierley
J
,
Gospodarowicz
MK
,
Wittekind
C
,
Ebscohost
. In:
Chichester
, editor.
TNM classification of malignant tumours
. 8th ed.
West Sussex, UK; Hoboken (NJ)
:
Wiley Blackwell/John Wiley & Sons, Inc
;
2017
.
13.
Kanda
Y
.
Investigation of the freely available easy-to-use software “EZR” for medical statistics
.
Bone Marrow Transplant
.
2013
;
48
(
3
):
452
8
. .
14.
Soussi
T
,
Legros
Y
,
Lubin
R
,
Ory
K
,
Schlichtholz
B
.
Multifactorial analysis of p53 alteration in human cancer: a review
.
Int J Cancer
.
1994
;
57
(
1
):
1
9
. .
15.
Angelopoulou
K
,
Stratis
M
,
Diamandis
EP
.
Humoral immune response against p53 protein in patients with colorectal carcinoma
.
Int J Cancer
.
1997
;
70
(
1
):
46
51
. .
16.
Tang
R
,
Ko
MC
,
Wang
JY
,
Changchien
CR
,
Chen
HH
,
Chen
JS
, et al
.
Humoral response to p53 in human colorectal tumors: a prospective study of 1,209 patients
.
Int J Cancer
.
2001
;
94
(
6
):
859
63
. .
17.
Shimada
H
,
Ochiai
T
,
Nomura
F
;
Japan p53 Antibody Research Group
.
Titration of serum p53 antibodies in 1,085 patients with various types of malignant tumors: a multiinstitutional analysis by the Japan p53 Antibody Research Group
.
Cancer
.
2003
;
97
(
3
):
682
9
. .
18.
Lechpammer
M
,
Lukac
J
,
Lechpammer
S
,
Kovacevic
D
,
Loda
M
,
Kusic
Z
.
Humoral immune response to p53 correlates with clinical course in colorectal cancer patients during adjuvant chemotherapy
.
Int J Colorectal Dis
.
2004
;
19
(
2
):
114
20
. .
19.
Suppiah
A
,
Greenman
J
.
Clinical utility of anti-p53 auto-antibody: systematic review and focus on colorectal cancer
.
World J Gastroenterol
.
2013
;
19
(
29
):
4651
70
. .
20.
Yamaguchi
T
,
Takii
Y
,
Maruyama
S
.
Usefulness of serum p53 antibody measurement in colorectal cancer: an examination of 1,384 primary colorectal cancer patients
.
Surg Today
.
2014
;
44
(
8
):
1529
35
. .
21.
Takahashi
R
,
Sakamoto
K
,
Sugimoto
K
,
Motegi
S
,
Tsukamoto
R
,
Ichikawa
R
, et al
.
Significance of serum p53 antibody as a tumor marker in colorectal cancer
.
Dis Markers
.
2019
;
2019
:
2721876
. .
22.
Broll
R
,
Duchrow
M
,
Oevermann
E
,
Wellm
C
,
Schwandner
O
,
Schimmelpenning
H
, et al
.
p53 autoantibodies in sera of patients with a colorectal cancer and their association to p53 protein concentration and p53 immunohistochemistry in tumor tissue
.
Int J Colorectal Dis
.
2001
;
16
(
1
):
22
7
. .
23.
Kumamoto
K
,
Ishida
H
,
Kuwabara
K
,
Amano
K
,
Chika
N
,
Okada
N
, et al
.
Clinical significance of serum anti-p53 antibody expression following curative surgery for colorectal cancer
.
Mol Clin Oncol
.
2017
;
7
(
4
):
595
600
. .
24.
Shimada
H
,
Shiratori
T
,
Takeda
A
,
Matsushita
K
,
Okazumi
S
,
Akutsu
Y
, et al
.
Perioperative changes of serum p53 antibody titer is a predictor for survival in patients with esophageal squamous cell carcinoma
.
World J Surg
.
2009
;
33
(
2
):
272
7
. .
25.
Kawahara
H
,
Watanabe
K
,
Enomoto
H
,
Toyama
Y
,
Akiba
T
,
Yanaga
K
.
Normalization of serum p53 antibody levels in patients after curative resection for colorectal cancer
.
Anticancer Res
.
2013
;
33
(
5
):
2221
5
.
26.
Park
YJ
,
Park
KJ
,
Park
JG
,
Lee
KU
,
Choe
KJ
,
Kim
JP
.
Prognostic factors in 2,230 Korean colorectal cancer patients: analysis of consecutively operated cases
.
World J Surg
.
1999
;
23
(
7
):
721
6
. .
27.
Sun
LC
,
Chu
KS
,
Cheng
SC
,
Lu
CY
,
Kuo
CH
,
Hsieh
JS
, et al
.
Preoperative serum carcinoembryonic antigen, albumin and age are supplementary to UICC staging systems in predicting survival for colorectal cancer patients undergoing surgical treatment
.
BMC Cancer
.
2009
;
9
:
288
. .
28.
Huh
JW
,
Oh
BR
,
Kim
HR
,
Kim
YJ
.
Preoperative carcinoembryonic antigen level as an independent prognostic factor in potentially curative colon cancer
.
J Surg Oncol
.
2010
;
101
(
5
):
396
400
. .
29.
World Medical Association
.
World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects
.
JAMA
.
2013
;
310
(
20
):
2191
4
. .
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