Immunohistochemical Expression of p53, Bcl-2, and Ki-67 Proteins in Traditional Serrated Adenomas of Colon

Jin Hwan Jung; Heon-Ju Kwon; Tae-Jung Kim; Hyung Jun Cho; Hye Kang Kim; Dae Young Cheung; Jin Il Kim; Jae Kwang Kim

doi:10.4166/kjg.2013.62.6.336

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Jung, Kwon, Kim, Cho, Kim, Cheung, Kim, and Kim: Immunohistochemical Expression of p53, Bcl-2, and Ki-67 Proteins in Traditional Serrated Adenomas of Colon

Original Article

Korean J Gastroenterol 2013;62(6):336-343.

Published online: 4 October 2013

DOI: https://doi.org/10.4166/kjg.2013.62.6.336

Immunohistochemical Expression of p53, Bcl-2, and Ki-67 Proteins in Traditional Serrated Adenomas of Colon

Jin Hwan Jung, Heon-Ju Kwon¹, Tae-Jung Kim², Hyung Jun Cho, Hye Kang Kim, Dae Young Cheung, Jin Il Kim, Jae Kwang Kim

Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea

¹Department of Radiology, Kangbuk Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

²Department of Hospital Pathology, The Catholic University of Korea, College of Medicine, Seoul, Korea

Correspondence to: Jin Il Kim, Department of Internal Medicine, The Catholic University of Korea, Yeouido St. Mary's Hospital, 10, 63-ro, Yeongdeungpo-gu, Seoul 150-713, Korea. Tel: +82-2-3779-1519, Fax: +82-2-3779-1331, E-mail: jikim@catholic.ac.kr

Received 14 September 2013 Revised 21 October 2013 Accepted 5 November 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

Serrated adenomas of the colon show mixed characteristics of both hyperplastic and adenomatous polyps. Serrated adenomas are known to progress via the serrated pathway than the adenoma-carcinoma pathway. The aim of this study was to evaluate the characteristics of traditional serrated adenomas compared to hyperplastic polyps and tubular adenomas by using immunohistochemical staining for p53, Bcl-2, and Ki-67.

Methods

Age, sex, location, size and the immunoexpression of p53, Bcl-2, and Ki-67 were retrospectively analyzed in 20 traditional serrated adenomas, 20 hyperplastic polyps, and 20 tubular adenomas from January 2007 to December 2012 at The Catholic University of Korea, Yeouido St. Mary's Hospital.

Results

There was no difference in Bcl-2 and p53 expression between traditional serrated adenomas and hyperplastic polyps. Ki-67 Expression of traditional serrated adenomas was higher than that of hyperplastic polyps (p=0.001). Ki-67 and p53 expression was similar between traditional serrated and tubular adenomas. Bcl-2 expression of traditional serrated adenomas was lower than that of tubular adenomas (p=0.001). Regarding the expression of p53, Bcl-2, and Ki-67 in traditional serrated adenomas, there were no statistical differences among age, sex, location, and size.

Conclusions

Our study suggested that Ki-67 may be helpful in distinguishing traditional serrated adenomas from hyperplastic polyps, and p53 expression may be ineffective in distinguishing between traditional serrated and tubular adenomas. From Bcl-2 expression, it is suggested that the tumorigenesis of traditional serrated adenomas is lower than that of tubular adenomas.

Keywords: Serrated adenoma, p53, Bcl-2, Ki-67

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Fig. 1.

Immunohistochemical staining of p53 in traditional serrated adenoma, hyperplastic polyp, and tubular adenoma. Intense nuclear staining of p53 is seen in traditional serrated adenoma (A, ×200) and tubular adenoma (C, ×200). However, p53 protein overexpression is not observed in hyperplastic polyp (B, ×200).

Fig. 2.

Immunohistochemical staining of Bcl-2 in traditional serrated adenoma, hyperplastic polyp, and tubular adenoma. Traditional serrated adenoma (A, ×200) and hyperplastic polyp (B, ×200) show loss of Bcl-2 expression. Tubular adenoma (C, ×200) shows cytoplasmic immunoreactivity for Bcl-2. Small lymphocytes in the lamina propria are internal control of Bcl-2 immunostaining.

Fig. 3.

Immunohistochemical staining of Ki-67 in traditional serrated adenoma, hyperplastic polyp, and tubular adenoma. Ki-67 positive cells (brown color) are seen at the bottom and on the surface of individual crypts of traditional serrated adenoma (A, ×200), hyperplastic polyp (B, ×200), and tubular adenoma (C, ×200).

Fig. 4.

Receiver operating characteristic analysis of Ki-67 level to identify traditional serrated adenomas. Area under the curve (AUC) was 0.808 (95% CI, 0.672–0.943) with cutoff point of 6%. Sensitivity=65%, specificity=80%.

Table 1.

Clinicopathologic Features of Patients with Traditional Serrated Adenomas, Tubular Adenomas, and Hyperplastic Polyps

Feature	Traditional serrated adenomas (n=20)	Hyperplastic polyps (n=20)	p-value	Tubular adenomas (n=20)	p-value
Age (yr)	59.4±11.5	65.9±12.2	0.091	62.1±8.1	0.397
Sex			＜1.000		＜1.000
Male	12 (60.0)	13 (65.0)		11 (55.0)
Female	8 (40.0)	7 (35.0)		9 (45.0)
Location			＜1.000		0.301
Proximal	4 (20.0)	4 (20.0)		8 (40.0)
Distal	16 (80.0)	16 (80.0)		12 (60.0)
Size (cm)	1.13±0.32	1.06±0.21	0.514	1.07±0.18	＜1.000
≤1	11 (55.0)	14 (70.0)		10 (50.0)
＞1	9 (45.0)	6 (30.0)		10 (50.0)

Values are presented as mean±SD or n (%).

Table 2.

Expressions of p53, Bcl-2, Ki-67 in Patients with Traditional Serrated Adenomas, Tubular Adenomas, and Hyperplastic Polyps

	Traditional serrated adenomas (n=20)	0) Hyperplastic polyps (n=20)	20) p-value Tu	ubular adenomas (n=2	0) p-value
p53 expression			0.487		＜1.000
Positive	2 (10.0)	0 (0)		3 (15.0)
Negative	18 (90.0)	20 (100.0)		17 (85.0)
Bcl-2 expression			0.342		0.001
Positive	4 (20.0)	1 (5.0)		15 (75.0)
Negative	16 (80.0)	19 (95.0)		5 (25.0)
Ki-67 labeling index (%)	14.85±12.45	4.45±3.43	0.001	16.15±16.84	0.783

Values are presented as n (%) or mean±SD.

Table 3.

Relationship between Clinicopathological Features and Expressions of p53, Bcl-2, Ki-67 in Traditional Serrated Adenomas

	n (%)	p53	p-value	Bcl-2	p-value	Ki-67 labeling index (%)	p-value
Age (yr)			0.495		0.619		0.483
＜60	12 (60.0)	2 (10.0)		3 (15.0)		16.50±12.44
≥60	8 (40.0)	0 (0)		1 (5.0)		12.38±12.87
Sex			0.495		0.619		0.667
Male	12 (60.0)	2 (10.0)		3 (15.0)		13.83±12.09
Female	8 (40.0)	0 (0)		1 (5.0)		16.38±13.65
Location			＜1.000		0.538		0.261
Proximal	4 (20.0)	0 (0)		0 (0)		21.25±14.36
Distal	16 (80.0)	2 (10.0)		4 (20.0)		13.25±11.89
Size (cm)			0.479		0.591		0.120
≤1	11 (55.0)	2 (10.0)		3 (15.0)		10.91±8.64
＞1	9 (45.0)	0 (0)		1 (5.0)		19.67±15.07

Values are presented as n (%) or mean±SD.

Table 4.

Expressions of p53, Bcl-2, Ki-67 in Traditional Serrated Adenomas with Low and High Grade Dysplasia

	TSALD (n=12) TSAHD (n=8)	p-value
p53 expression		0.147
Positive	2 (25.0)0 (0)
Negative	6 (75.0)12 (100.0)
Bcl-2 expression		0.014
Positive	4 (50.0)0 (0)
Negative	4 (50.0)12 (100.0)
Ki-67 labeling index (%)	12.83±10.50 17.88±15.16	0.389

Values are presented as n (%) or mean±SD. TSALD, traditional serrated adenomas with low grade dysplasia; TSAHD, traditional serrated adenomas with high grade dysplasia.

Table 5.

Expressions of p53, Bcl-2, Ki-67 in Tubular Adenomas with Low and High Grade Dysplasia

	TALD (n=10)	TAHD (n=10)	p-value
p53 expression			0.211
Positive	0 (0)	3 (30.0)
Negative	10 (100.0)	7 (70.0)
Bcl-2 expression			＜1.000
Positive	7 (70.0)	8 (80.0)
Negative	3 (30.0)	2 (20.0)
Ki-67 labeling index	(%) 9.30±11.26	23.00±19.18	0.067

TALD, tubular adenomas with low grade dysplasia; TAHD, tubular adenomas with high grade dysplasia.

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