Ji Hoon Kim; Dae Yoon Eom; Chan Wook Kim; Nam Kyu Choi; Jin Ho Kwak; Gun Moo Choi; Hyuck Jae Jang; Myung Sik Han

doi:10.4174/jkss.2011.80.1.29

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Kim, Eom, Kim, Choi, Kwak, Choi, Jang, and Han: Expression of E-cadherin, β-catenin, Cdx2 and MMP7 in pT2 and N1/N2 Gastric Cancer: Relationship with Tumor Recurrence within 2-Year Period

Original Article

Journal of Korean Spine Surg 2011;80(1):29-35.

Published online: 4 February 2011

DOI: https://doi.org/10.4174/jkss.2011.80.1.29

Expression of E-cadherin, β-catenin, Cdx2 and MMP7 in pT2 and N1/N2 Gastric Cancer: Relationship with Tumor Recurrence within 2-Year Period

Ji Hoon Kim, M.D., Dae Yoon Eom, M.D.¹, Chan Wook Kim, M.D., Nam Kyu Choi, M.D., Jin Ho Kwak, M.D., Gun Moo Choi, M.D., Hyuck Jae Jang, M.D., Myung Sik Han, M.D.

Department of Surgery, College of Medicine, University of Ulsan, Gangneung Asan Hospital, Gangneung, Korea

¹Department of Pathology, College of Medicine, University of Ulsan, Gangneung Asan Hospital, Gangneung, Korea

책임저자: 김지훈, 강원도 강릉시 사천면 방동리 415? 210-711, 울산대학교 강릉아산병원 외과 Tel: 033-610-3220, Fax: 033-610-4960 E-mail: cibax@gnah.co.kr

Received 28 October 2010 Accepted 8 December 2010

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

Purpose

The aim of this study was to examine the expression of E-cadherin, β-catenin, Cdx2, MMP7 in gastric cancer and to evaluate the clinical significance of these molecules in tumor recurrence within 2 years of pT2 and N1/N2 gastric cancer.

Methods

In 122 patients who underwent radical resection of gastric cancer, we investigated the association between the expression of these molecules and clinicopathologic factors by immunohistochemistry. The included criteria were pT2 and N1 or N2 (6th AJCC TNM).

Results

The expression of MMP7 was significantly associated with N stage (N1 vs. N2) (P=0.011). The negative expression of β-catenin was strongly correlated with tumor recurrence within a 2-year period. However, the expression of these molecules was not related with recurrent sites. Multivariate analysis demonstrated that negative expression of β-catenin was an independent predictor for tumor recurrence within 2 years (OR 2.366; 95%CI 1.056∼5.297; P=0.036).

Conclusion

Negative expression of β-catenin may serve as a significant indicator for predicting tumor recurrence within a 2-year period in pT2 and N1/N2 gastric cancer.

Keywords: E-cadherin, β-catenin, Cdx2, MMP7, Gastric cancer

References

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Fig. 1.

Representative images of H&E stain and immunohistochemistry of E-cadherin, β-catenin, Cdx2 and MMP7. (A) Moderately differentiated adenocarcinoma is noted (H&E stain, ×200). (B) The tumor cells are positive in the cell membrane for E-cadherin (Immunohistochemistry, ×400). (C) Aberrant β-catenin expression (cytoplasmic and nuclear accumulation) is noted (Immunohistochemistry, ×400). (D) The tumor cells are positive in the nuclei for Cdx2 (Immunohistochemistry, ×400). (E) The tumor cells are positive in the cytoplasm for the MMP7 (Immunohisto-chemistry, ×400).

Table 1.

Relationship between the results of immunohistochemistry and clinicopathological features

	E-cadherin		β-catenin		Cdx2		MMP7
	Negative	Positive	Negative	Positive	Negative	Positive	Negative	Positive
	N=67	N=55	N=55	N=67	N=42	N=80	N=47	N=75
Age
≤65	19	28	20	27	18	29	22	25
＞65	48	27	35	40	24	51	25	50
	P=0.015		P=0.711		P=0.558		P=0.181
Gender
Male	54	38	47	45	34	58	24	58
Female	13	17	8	22	8	22	13	17
	P=0.205		P=0.022		P=0.379		P=0.666
Histological
Differentiated	38	22	26	34	16	44	18	42
Undifferentiated	d 29	33	29	33	26	36	29	33
	P=0.072		P=0.720		P=0.088		P=0.065
Depth
T2a	12	17	14	15	12	17	9	20
T2b	55	38	41	52	30	63	38	55
	P=0.134		P=0.831		P=0.379		P=0.389
N stage
N1	42	36	32	46	25	53	37	41
N2	25	19	23	21	17	27	10	34
	P=0.850		P=0.259		P=0.552		P=0.011
Size
≤5 cm	35	26	29	32	21	40	25	36
＞5 cm	32	29	26	35	21	40	22	39
	P=0.716		P=0.716		P=1.000		P=0.710

Table 2.

Relationship between the results of immunohistochemistry and 2-year disease free survival rate (2YDFSR)

	E-cadherin		β-catenin		Cdx2		MMP7
	Negative	Positive	Negative	Positive	Negative	Positive	Negative	Positive
	N=63	N=51	N=50	N=64	N=36	N=78	N=41	N=73
Recurrence within 2-Year	24	12	21	15	11	25	9	27
2YDFSR (%)	61.9	76.5	58.0	76.6	69.4	67.9	78.0	63.0
P-value	0.172		0.044		0.763		0.103

Table 3.

Relationship between the results of immunohistochemistry and recurrent sites

	E-cadherin		β-catenin		Cdx2		MMP7
	Negative	Positive	Negative	Positive	Negative	Positive	Negative	Positive
	N=63	N=51	N=50	N=64	N=36	N=78	N=41	N=73
Peritoneum	3	9	5	7	4	8	3	9
	P=0.221		P=0.361		P=1.000		P=0.532
Liver	6	9	6	9	4	11	4	11
	P=0.785		P=0.264		P=0.772		P=0.567
Lymph node	2	5	3	4	2	5	2	5
	P=0.457		P=0.697		P=1.000		P=1.000
Lung	0	1	0	1	0	1	0	1
	P=1.000		P=0.439		P=1.000		P=1.000
Bone	1	0	1	0	1	0	0	1
	P=0.447		P=1.000		P=0.316		P=1.000

Table 4.

Univariate and multivariate analysis with respect to 2-year disease free survival rate

		Univariate P-value	Odds ratio	Multivariate 95% CI	P-value
Age	≤65 vs. ＞65	0.406
Gender	Male vs. Female	0.834
Histological	Differentiated vs. Undifferentiated	0.928
Depth	T2a vs. T2b	0.122
N stage	N1 vs. N2	0.074			NS
Size	≤5 cm vs. ＞5 cm	0.112
E-cadherin	Negative vs. Positive	0.172
β-catenin	Negative vs. Positive	0.044	2.366	1.056∼5.297	0.036
Cdx2	Negative vs. Positive	0.763
MMP7	Negative vs. Positive	0.103

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