Tadokoro H, Shigihara T, Ikeda T, Takase M, Suyama M. Two distinct pathways of p16 gene inactivation in gallbladder cancer. World J Gastroenterol 2007; 13(47): 6396-6403 [PMID: 18081229 DOI: 10.3748/wjg.v13.i47.6396]
Corresponding Author of This Article
Hiroyuki Tadokoro, MD, Department of Gastroenterology, Juntendo Tokyo Koto Geriatric Medical Center, 3-3-20 Shinsuna, Koto-ku, Tokyo 136-0075, Japan. heroyou27@yahoo.co.jp
Article-Type of This Article
Clinical Research
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Dec 21, 2007; 13(47): 6396-6403 Published online Dec 21, 2007. doi: 10.3748/wjg.v13.i47.6396
Table 1 The primer sequence of the p16 genes
Exon
Primer sequence
Size(bp)
Anneling temperature (°C)
Exon1α
F: 5'-GAGAGGGGGAGAGCAGGCAG-3'
250
58
R: 5'-GCAAACTTCGTCCTCCAGAGT-3'
Exon2-1
F: 5'-AGCTTCCTTTCCGTCATGC-3'
203
56
R: 5'-GCAGCACCACCAGCGTG-3'
Exon2-2
F: 5'-AGCCCAACTGCGCCGAC-3'
147
58
R: 5'-CCAGGTCCACGGGCAGA-3'
Exon2-3
F: 5'-TGGACGTGCGCGATGC-3'
189
56
R: 5'-GGAAGCTCTCAGGGTACAAATTC-3'
Exon3
F: 5'-CCGGTAGGGACGGCAAGAGA-3'
169
58
R: 5'-CTGTAGGACCCTCGGTGACTGATGA-3'
Table 2 Association between p16 alterations and clinicopathological variables in gallbladder cancers
Clinicopathological variables
p16 protein expression
Methylation of p16INK4a
LOH at 9p21-22
Homozygous deletion of p16 gene
Absent n
Present n
P
Absent n
Present n
P
Retension n
LOH n
P
Absent n
Present n
P
Age
< 65
13
7
0.789
5
15
0.753
10
10
0.427
13
6
0.481
> 65
19
12
9
22
12
19
24
7
Gender
Female
14
11
0.329
6
19
0.588
10
15
0.657
20
4
0.148
Male
18
8
8
18
12
14
17
9
Tumor type
Adenocarcinoma
28
18
0.401
14
32
0.148
19
27
0.423
35
10
0.068
Adenosquamous
4
1
0
5
3
2
2
3
Differentiation grade
Well-Moderate
22
17
0.144
12
27
0.907
18
21
0.115
29
10
0.16
Poor
6
1
2
5
1
6
6
0
Stage
0 and IA, IB
15
13
0.135
9
19
0.407
15
13
0.097
20
7
0.99
IIA and IIB
17
6
5
18
7
16
17
6
T factor
Tis and T1
6
6
0.296
3
9
0.828
8
4
0.060
11
1
0.11
T2 and T3
26
13
11
28
14
25
26
12
N factor
N0
21
16
0.150
9
28
0.416
19
18
0.054
28
8
0.329
N1
11
3
5
9
3
11
9
5
Table 3 Association between p16 protein expression and 9p21-22
p16 protein expression
Negative
Positive
P
LOH (-)
12
10
LOH (+)
20
9
0.292
Table 4 Association between p16 protein expression and LOH at 9p21
p16 protein expression
Negative
Positive
P
LOH (-)
16
16
LOH (+)
16
3
0.0146
Table 5 Association between p16 immunohistochemistry and p16 alterations in gallbladder cancers
p16 immunohistochemistry
Positive
Negative
P
Retension
3
3
Hypermethyaltion
9
6
LOH
1
3
LOH (multiple) + Hypermethylation
2
8
Multiple LOH
0
3
Homozygous deletion
4
9
P < 0.05
Citation: Tadokoro H, Shigihara T, Ikeda T, Takase M, Suyama M. Two distinct pathways of p16 gene inactivation in gallbladder cancer. World J Gastroenterol 2007; 13(47): 6396-6403