Introduction: Squamous cell carcinoma is the most common cancer of the oral cavity. When the tumor invades the bone tissue, the prognostic and survival rates decrease a lot, and the treatment becomes more aggressive, with several damages to the patient and health system. Many of the molecular mechanisms of bone invasion process are not understood yet, but it is already known that one of central processes of tumor evolution – adjacent tissues invasion and metastasis – is a large spectrum of phenotypic changes in epithelial cells to mesenchymal, in a process named as epithelial-mesenchymal transition (EMT). Loss of E-cadherin, an important epithelial cell adhesion protein, is a hallmark of this phenomenon. The objective of this retrospective study is to evaluate the expression of E-cadherin protein, comparing its distribution with clinical characteristics of the patients and possibly relation to EMT. Methods: Sixty-two cases with respective clinical data were analyzed by comparing immunohistochemical, H and E staining, and clinical data, observing the tumor-bone interface (TBI) and the surrounding tumor that had no direct contact with the bone surface (ST). Results: Forty cases were positive for E-cadherin (64%) with a heterogeneous pattern. Statistical analysis showed a significant difference between the presence of E-cadherin expression and tobacco smokers. Also, the equal or weaker protein expression in the ST than TBI is related to a worse overall survival. No statistically significant difference in other prognostic factors was observed. Conclusion: Our results suggest that the tumor cells that interact with the bone tissue could gain molecular changes, like partial EMT and osteoclastogenesis induction, which facilitate their migration and increase the bone resorption, resulting in a worse patient’s prognosis.

1.
Siegel
RL
,
Miller
KD
,
Fedewa
SA
,
Ahnen
DJ
,
Meester
RGS
,
Barzi
A
,
Colorectal cancer statistics, 2017
.
CA Cancer J Clin
.
2017
;
67
(
3
):
177
93
. .
2.
Gupta
K
,
Metgud
R
.
Evidences suggesting involvement of viruses in oral squamous cell carcinoma
.
Patholog Res Int
.
2013
;
2013
:
642496
. Available from: .
3.
Gigliotti
J
,
Madathil
S
,
Makhoul
N
.
Delays in oral cavity cancer
.
Int J Oral Maxillofac Surg
.
2019
;
48
(
9
):
1131
7
. .
4.
Howlader
NNA
,
Krapcho
M
,
Miller
D
,
Bishop
K
,
Kosary
CL
,
Yu
M
,
SEER cancer statistics review, 1975–2014
. Available from: https://seer.cancer.gov.csr/1975_2014/.
5.
Vasconcelos
JA
,
Vergnhanini
GS
,
Contreiro
PF
,
Kanda
JL
,
Akerman
M
,
Matos
LL
.
Epidemiologia do câncer de cabeça e pescoço no Brasil : estudo transversal de base populacional
.
Rev Bras Cir Cabeça Pescoço
.
2012
;
41
:
186
91
.
6.
Brown
JS
,
Lowe
D
,
Kalavrezos
N
,
D'Souza
J
,
Magennis
P
,
Woolgar
J
.
Patterns of invasion and routes of tumor entry into the mandible by oral squamous cell carcinoma
.
Head Neck
.
2002
;
24
(
4
):
370
83
. .
7.
Yao
CMKL
,
Chang
EI
,
Lai
SY
.
Contemporary approach to locally advanced oral cavity squamous cell carcinoma
.
Curr Oncol Rep
.
2019
;
21
(
11
):
1
9
. .
8.
Jimi
E
,
Furuta
H
,
Matsuo
K
,
Tominaga
K
,
Takahashi
T
,
Nakanishi
O
.
The cellular and molecular mechanisms of bone invasion by oral squamous cell carcinoma
.
Oral Dis
.
2011
;
17
(
5
):
462
8
. .
9.
Guise
TA
,
Mundy
GR
.
Cancer and bone
.
Endocr Rev
.
1998 Feb
;
19
(
1
):
18
54
. Available from: .
10.
Quan
J
,
Johnson
NW
,
Zhou
G
,
Parsons
PG
,
Boyle
GM
,
Gao
J
.
Potential molecular targets for inhibiting bone invasion by oral squamous cell carcinoma: a review of mechanisms
.
Cancer Metastasis Rev
.
2012
;
31
(
1–2
):
209
19
. Available from: .
11.
Shaw
RJ
,
Brown
JS
,
Woolgar
JA
,
Lowe
D
,
Rogers
SN
,
Vaughan
ED
.
The influence of the pattern of mandibular invasion on recurrence and survival in oral squamous cell carcinoma
.
Head Neck
.
2004
;
26
(
10
):
861
9
. .
12.
Thiery
JP
.
Epithelial-mesenchymal transitions in tumour progression
.
Nat Rev Cancer
.
2002 Jun
;
2
(
6
):
442
54
. Available from: .
13.
Jimi
E
,
Furuta
H
,
Matsuo
K
,
Tominaga
K
,
Takahashi
T
,
Nakanishi
O
.
The cellular and molecular mechanisms of bone invasion by oral squamous cell carcinoma
.
Oral Dis
.
2011
;
17
(
5
):
462
8
. .
14.
Morra
L
,
Moch
H
.
Periostin expression and epithelial-mesenchymal transition in cancer: a review and an update
.
Virchows Arch
.
2011
;
459
(
5
):
465
75
. .
15.
Chen
WC
,
Obrink
B
.
Cell-cell contacts mediated by E-cadherin (uvomorulin) restrict invasive behavior of L-cells
.
J Cell Biol
.
1991 Jul
;
114
(
2
):
319
27
. Available from: .
16.
Oka
H
,
Shiozaki
H
,
Kobayashi
K
,
Inoue
M
,
Tahara
H
,
Kobayashi
T
,
Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis
.
Cancer Res
.
1993 Apr 1
;
53
(
7
):
1696
701
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8453644.
17.
Tamura
S
.
The E-cadherin-mediated cell-cell adhesion system in human cancers
.
Br J Surg
.
1997 Jul
;
84
(
7
):
899
900
. Available from: .
18.
Rivera
C
.
Essentials of oral cancer
.
Int J Clin Exp Pathol
.
2015
;
8
(
9
):
11884
94
.
19.
Ozaki-Honda
Y
,
Seki
S
,
Fujiwara
M
,
Matsuura
M
,
Fujita
S
,
Ikeda
H
,
Prognostic prediction of oral squamous cell carcinoma by E-Cadherin and N-Cadherin expression in overall cells in tumor nests or tumor cells at the invasive front
.
Cancer Microenviron
.
2017
;
10
(
1–3
):
87
94
. .
20.
Shetty
D
,
Jayade
BV
,
Joshi
SK
,
Gopalkrishnan
K
.
Accuracy of palpation, ultrasonography, and computed tomography in the evaluation of metastatic cervical lymph nodes in head and neck cancer
.
Indian J Dent
.
2015
;
6
(
3
):
121
4
. Available from: .
21.
Kuk
SK
,
Yoon
HJ
,
Hong
SD
,
Hong
SP
,
Lee
JI
.
Staging significance of bone invasion in small-sized (4 cm or less) oral squamous cell carcinoma as defined by the American joint committee on cancer
.
Oral Oncol
.
2016 Apr
;
55
:
31
6
. Available from: .
22.
Fives
C
,
Nae
A
,
Roche
P
,
O'Leary
G
,
Fitzgerald
B
,
Feeley
L
,
Impact of mandibular invasion on prognosis in oral squamous cell carcinoma four centimeters or less in size
.
Laryngoscope
.
2017
;
127
(
4
):
849
54
. .
23.
Ebrahimi
A
,
Murali
R
,
Gao
K
,
Elliott
MS
,
Clark
JR
.
The prognostic and staging implications of bone invasion in oral squamous cell carcinoma
.
Cancer
.
2011
;
117
(
19
):
4460
7
. .
24.
Adel
M
,
Kao
HK
,
Hsu
CL
,
Huang
JJ
,
Lee
LY
,
Huang
Y
,
Evaluation of lymphatic and vascular invasion in relation to clinicopathological factors and treatment outcome in oral cavity squamous cell carcinoma
.
Medicine
.
2015 Oct
;
94
(
43
):
e1510
. Available from: .
25.
Zhou
J
,
Tao
D
,
Xu
Q
,
Gao
Z
,
Tang
D
.
Expression of E-cadherin and vimentin in oral squamous cell carcinoma
.
Int J Clin Exp Pathol
.
2015
;
8
(
3
):
3150
4
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26045832.
26.
Greenburg
G
,
Hay
ED
.
Epithelia suspended in collagen gels can lose polarity and express characteristics of migrating mesenchymal cells
.
J Cell Biol
.
1982 Oct
;
95
(
1
):
333
9
. Available from: .
27.
Lamprecht
S
,
Kaller
M
,
Schmidt
EM
,
Blaj
C
,
Schiergens
TS
,
Engel
J
,
PBX3 Is part of an EMT regulatory network and indicates poor outcome in colorectal cancer
.
Clin Cancer Res
.
2018
;
24
(
8
):
1974
86
. Available from: .
28.
Zhu
H
,
Gu
Y
,
Xue
Y
,
Yuan
M
,
Cao
X
,
Liu
Q
.
CXCR2+ MDSCs promote breast cancer progression by inducing EMT and activated T cell exhaustion
.
Oncotarget
.
2017 Dec 29
;
8
(
70
):
114554
67
. Available from: .
29.
Brabletz
T
,
Kalluri
R
,
Nieto
MA
,
Weinberg
RA
.
EMT in cancer
.
Nat Rev Cancer
.
2018
;
18
(
2
):
128
34
. Available from: .
30.
Fiorino
C
,
Harrison
RE
.
E-cadherin is important for cell differentiation during osteoclastogenesis
.
Bone
.
2016
;
86
:
106
18
. .
31.
Quan
J
,
Du
Q
,
Hou
Y
,
Wang
Z
,
Zhang
J
.
Utilization of E-cadherin by monocytes from tumour cells plays key roles in the progression of bone invasion by oral squamous cell carcinoma
.
Oncol Rep
.
2017
;
38
(
2
):
850
8
. .
32.
Shibahara
T
,
Nomura
T
,
Cui
NH
,
Noma
H
.
A study of osteoclast-related cytokines in mandibular invasion by squamous cell carcinoma
.
Int J Oral Maxillofac Surg
.
2006
;
34
(
7
):
789
93
. .
33.
Kayamori
K
,
Sakamoto
K
,
Nakashima
T
,
Takayanagi
H
,
Morita
K
,
Omura
K
,
Roles of interleukin-6 and parathyroid hormone-related peptide in osteoclast formation associated with oral cancers: significance of interleukin-6 synthesized by stromal cells in response to cancer cells
.
Am J Pathol
.
2010
;
176
(
2
):
968
80
. .
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