Background: Mild cellular atypia of esophageal squamous epithelial dysplasia has a risk of progressing to cancer that poses great confusion for pathological diagnosis. There is no research on the diagnosis and differential diagnosis of esophageal squamous dysplasia by the expression of immunohistochemical (IHC) p53. The study aims to conduct a graded diagnosis of esophageal squamous epithelial hyperplasia by combining p53 expressions and microscopic histomorphological characteristics. Methods: The study was conducted from January 2021 to January 2022 and included a total of 208 cases including 262 specimens with atypical hyperplasia or dysplasia of squamous epithelia discovered by esophageal mucosal biopsy. HE staining was used to grade the epithelial hyperplasia degree, and all cases underwent p53 IHC evaluation. Results: Benign lesions: we did not find any p53 IHC mutant-phenotype (0/12 cases) in 12 cases of esophagitis. We found 10 cases (10/80 cases) of p53 IHC mutant-phenotype in 80 cases of low-grade dysplasia, and 158 cases (158/170 cases) of p53 IHC mutant-phenotype of high-grade lesions in 170 cases of high-grade dysplasia and early cancer based on the χ2 test results. We found statistically significant differences in p53 IHC mutant-phenotype between the high-grade squamous epithelial lesions and benign lesions. The sensitivity and specificity of p53 in detecting high-grade squamous epithelial lesions were 92.9% and 89.1%, respectively. The positive predictive value was 94.0%, and the negative predictive value was 87.2%. Conclusion: In this study, we found that p53 IHC had high sensitivity and specificity in detecting high-grade esophageal squamous epithelial lesions. Therefore, it has potential to be used as a routine item in pathological detection for auxiliary risk stratification of esophageal squamous epithelial lesions.

1.
Bray
F
,
Ferlay
J
,
Soerjomataram
I
,
Siegel
RL
,
Torre
LA
,
Jemal
A
.
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries
.
CA Cancer J Clin
.
2018
;
68
(
6
):
394
424
. [published correction appears in CA Cancer J Clin. 2020 Jul;70(4):313].
2.
Itabashi
M
,
Nasierowska-Guttmejer
A
,
Shimoda
T
,
Majewski
P
,
Rezner
W
,
Sikora
K
.
The importance of the concept and histological criteria of “intraepithelial squamous cell carcinoma” of the esophagus: in comparison between Western and Japanese criteria
.
Esophagus
.
2017
;
14
(
4
):
333
42
.
3.
Shcherbynina
M
,
Itabashi
M
,
Soloviova
N
.
Histological criteria for “intraepithelial squamous cell carcinoma” of the esophagus: continued dialogue between Ukrainian and Japanese pathologists
.
Exp Oncol
.
2020
;
42
(
4
):
314
7
.
4.
Chen
XX
,
Zhong
Q
,
Liu
Y
,
Yan
SM
,
Chen
ZH
,
Jin
SZ
.
Genomic comparison of esophageal squamous cell carcinoma and its precursor lesions by multi-region whole-exome sequencing
.
Nat Commun
.
2017
;
8
(
1
):
524
.
5.
Kobayashi
S
,
Yamaguchi
T
,
Maekawa
S
,
Takano
S
,
Kuno
T
,
Tanaka
K
.
Target sequencing of cancer-related genes in early esophageal squamous neoplasia resected by endoscopic resection in Japanese patients
.
Oncotarget
.
2018
;
9
(
95
):
36793
803
.
6.
Savant
D
,
Zhang
Q
,
Yang
Z
.
Squamous neoplasia in the esophagus
.
Arch Pathol Lab Med
.
2021
;
145
(
5
):
554
61
.
7.
Takubo
K
,
Fujii
S
Oesophageal squamous dysplasia [M]/ edited by the WHO Classification of Tumours Editorial Board. WHO classification of tumours. Digestive system tumours
5th ed
Lyon
IARC Press
2019
. p.
36
7
.
8.
Japan Esophageal Society
.
Japanese classification of esophageal cancer, 11th edition: part II and III
.
Esophagus
.
2017
;
14
(
1
):
37
65
.
9.
Japan Esophageal Society
.
Japanese classification of esophageal cancer, 11th edition: part I
.
Esophagus
.
2017
;
14
(
1
):
1
36
.
10.
Köbel
M
,
Kang
EY
.
The many uses of p53 immunohistochemistry in gynecological pathology: proceedings of the ISGyP companion society session at the 2020 USCAP Annual9 meeting
.
Int J Gynecol Pathol
.
2021
;
40
(
1
):
32
40
.
11.
Tessier-Cloutier
B
,
Kortekaas
KE
,
Thompson
E
,
Pors
J
,
Chen
J
,
Ho
J
.
Major p53 immunohistochemical patterns in in situ and invasive squamous cell carcinomas of the vulva and correlation with TP53 mutation status
.
Mod Pathol
.
2020
;
33
(
8
):
1595
605
.
12.
Ishihara
R
,
Arima
M
,
Iizuka
T
,
Oyama
T
,
Katada
C
,
Kato
M
.
Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer
.
Dig Endosc
.
2020
;
32
(
4
):
452
93
.
13.
Goda
K
,
Dobashi
A
,
Yoshimura
N
,
Chiba
M
,
Fukuda
A
,
Nakao
Y
.
Clinicopathological features of narrow-band imaging endoscopy and immunohistochemistry in ultraminute esophageal squamous neoplasms
.
Dis Esophagus
.
2014
;
27
(
3
):
267
75
.
14.
Zheng
JY
,
Chen
YH
,
Chen
YY
,
Zheng
XL
,
Zhong
SS
,
Deng
WY
.
Presence of pink-color sign within 1 min after iodine staining has high diagnostic accordance rate for esophageal high-grade intraepithelial neoplasia/invasive cancer
.
Saudi J Gastroenterol
.
2019
;
25
(
2
):
113
8
.
15.
Tack
J
,
Pandolfino
JE
.
Pathophysiology of gastroesophageal reflux disease
.
Gastroenterology
.
2018
;
154
(
2
):
277
88
.
16.
Singh
N
,
Piskorz
AM
,
Bosse
T
,
Jimenez-Linan
M
,
Rous
B
,
Brenton
JD
.
p53 immunohistochemistry is an accurate surrogate for TP53 mutational analysis in endometrial carcinoma biopsies
.
J Pathol
.
2020
;
250
(
3
):
336
45
.
17.
Gao
YB
,
Chen
ZL
,
Li
JG
,
Hu
XD
,
Shi
XJ
,
Sun
ZM
.
Genetic landscape of esophageal squamous cell carcinoma
.
Nat Genet
.
2014
;
46
(
10
):
1097
102
.
18.
Hayashi
A
,
Yashima
K
,
Takeda
Y
,
Sasaki
S
,
Kawaguchi
K
,
Harada
K
.
Fhit, E-cadherin, p53, and activation-induced cytidine deaminase expression in endoscopically resected early stage esophageal squamous neoplasia
.
J Gastroenterol Hepatol
.
2012
;
27
(
11
):
1752
8
.
19.
Liu
X
,
Zhang
M
,
Ying
S
,
Zhang
C
,
Lin
R
,
Zheng
J
.
Genetic alterations in esophageal tissues from squamous dysplasia to carcinoma
.
Gastroenterology
.
2017
;
153
(
1
):
166
77
.
20.
Rong
LL
,
Xue
LY
,
Xue
XM
,
Li
J
,
Lyu
N
.
The expression of p53 protein and its clinicopathological features and prognosis of esophageal spindle cell carcinoma
.
Chin J Pathol
.
2020
;
49
(
7
):
715
20
.
21.
Hou
WH
,
Duan
XK
,
Hou
WD
,
Ma
LJ
,
Niu
JW
,
Zhou
SL
.
Clinicopathological features of basal cell type dysplasia of esophagus
.
Chin J Pathol
.
2021
;
50
(
6
):
638
44
.
22.
Hou
WH
,
Duan
XK
,
Hou
WD
,
Shen
MQ
,
Zhang
XL
,
Liu
YF
.
Clinicopathological features of basal cell layer type high-grade squamous dysplasia of the esophagus
.
Chin J Pathol
.
2021
;
50
(
3
):
236
41
.
23.
Hou
WH
,
Shen
MQ
,
Hou
WD
,
Zhang
XL
,
Jin
ML
.
Clinicopathological features of differentiated-type dysplasia of the esophagus
.
Chin J Pathol
.
2021
;
50
(
12
):
1353
9
.
24.
Hou
WH
,
Shen
MQ
,
Hou
WD
,
Zhang
XL
,
Niu
JW
,
Zhou
SL
.
Spindle cell type squamous dysplasia of the esophagus:a clinicopathological analysis
.
Zhonghua Bing Li Xue Za Zhi
.
2021
;
50
(
10
):
1128
33
.
25.
Wang
WC
,
Wu
TT
,
Chandan
VS
,
Lohse
CM
,
Zhang
L
.
Ki-67 and ProExC are useful immunohistochemical markers in esophageal squamous intraepithelial neoplasia
.
Hum Pathol
.
2011
;
42
(
10
):
1430
7
.
26.
Shimizu
Y
,
Yoshida
T
,
Kato
M
,
Hirota
J
,
Ono
S
,
Nakagawa
M
.
Low-grade dysplasia component in early invasive squamous cell carcinoma of the esophagus
.
J Gastroenterol Hepatol
.
2010
;
25
(
2
):
314
8
.
27.
Denning
KL
,
Al-Subu
A
,
Elitsur
Y
.
Immunoreactivity of p53 and Ki-67 for dysplastic changes in children with eosinophilic esophagitis
.
Pediatr Dev Pathol
.
2013
;
16
(
5
):
331
6
.
28.
Zhu
XN
,
Dong
PW
,
Xiang
LY
,
Zhu
LL
,
Wang
YP
.
Risk factors for missed diagnosis of esophageal low-grade intraepithelial neoplasia in endoscopic forceps biopsy compared with endoscopic submucosal dissection
.
Sichuan Da Xue Xue Bao Yi Xue Ban
.
2018
;
49
(
6
):
854
8
.
29.
Sang
HM
,
Cao
JL
,
Soyfoo
MD
,
Zhang
WM
,
Jiang
JX
,
Xu
SF
.
Endoscopic and histopathology characteristics in patients with esophageal high-grade intraepithelial neoplasia
.
Dig Surg
.
2019
;
36
(
5
):
384
93
.
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