Prognostic Significance of Ki-67 Expression in Patients Undergoing Surgical Resection for Gastrointestinal Stromal Tumor

Seong Yeon Jeong; Won Wo Park; You Sun Kim; Young Il Park; Seung Hyup Kim; Won Jae Yoon; Jeong Seop Moon; Byung Mo Lee; Seong Woo Hong; Yun Kyung Kang

doi:10.4166/kjg.2014.64.2.87

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Jeong, Park, Kim, Park, Kim, Yoon, Moon, Lee, Hong, and Kang: Prognostic Significance of Ki-67 Expression in Patients Undergoing Surgical Resection for Gastrointestinal Stromal Tumor

Original Article

Korean J Gastroenterol 2014;64(2):87-92.

Published online: 4 October 2014

DOI: https://doi.org/10.4166/kjg.2014.64.2.87

Prognostic Significance of Ki-67 Expression in Patients Undergoing Surgical Resection for Gastrointestinal Stromal Tumor

Seong Yeon Jeong^*, Won Wo Park^*, You Sun Kim, Young Il Park, Seung Hyup Kim, Won Jae Yoon, Jeong Seop Moon, Byung Mo Lee¹, Seong Woo Hong¹, Yun Kyung Kang²

Department of Internal Medicine, Inje University College of Medicine, Seoul, Korea

¹Department of Surgery, Inje University College of Medicine, Seoul, Korea

²Department of Pathology, Inje University College of Medicine, Seoul, Korea

Correspondence to: You Sun Kim, Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, 9 Mareunnae-ro, Jung-gu, Seoul 100-032, Korea. Tel: +82-2-2270-0012, Fax: +82-2-2270-0257, E-mail: yousunk69@korea.com

^* These two authors equally contributed to this work as the co-first author.

Received 19 February 2014 Revised 19 June 2014 Accepted 19 June 2014

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

Assessment of malignant potential in gastrointestinal stromal tumor (GIST) is still problematic. The maximum tumor diameter and the mitotic index are generally used as an index of malignancy of GISTs. The Ki-67 labeling index has recently been used as an index of cell growth. The aim of this study was to investigate the prognostic value of Ki-67 in GIST.

Methods

We retrospectively reviewed the medical records of 32 patients with GIST who underwent surgical resection at Inje University Seoul Paik Hospital. We analyzed their Ki-67 expression, histologic finding, and prognosis.

Results

According to the tumor size and mitotic count, 4 patients were classified as very low risk, 9 patients as low risk, 14 patients as intermediate risk and 5 patients as high risk. The average Ki-67 index was 5.56±4.48%. The median follow-up duration was 35.72±29.04 months, and local/distant recurrences were observed in 6 (18.7%) patients. The overall cumulative disease free survival rates in patients with Ki-67 index ≤5% at 1 year, 2 years, and 5 years were 100%, 100%, and 86%, respectively. The overall cumulative disease free survival rates in patients with Ki-67 index ＞5% were at 1 year, 2 years, and 5 years were 82.1%, 70.3%, and 46.9%, respectively. There was significant relationship between elevated Ki-67 and disease free survival rate (p=0.007).

Conclusions

Our study suggests that Ki-67 index ＞5% confers a higher risk of relapse in patients with GIST. Future work should focus on standardization of Ki-67 assessment and specification of its role in making treatment decisions.

Keywords: Gastrointestinal stromal tumors, Ki-67 antigen, Prognosis

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Fig. 1.

Immunohistochemical staining for Ki-67 (×100). (A) Ki-67 index ≤5%. (B) Ki-67 index ＞5%.

Fig. 2.

Kaplan-Meier curves show that Ki-67 index ＞5% confers a higher risk of relapse in patients with gastrointestinal stromal tumor (p=0.007).

Fig. 3.

Correlation between tumor size and Ki-67 index. Spearman's rank correlation coefficient r=0.174 (p＜0.174).

Fig. 4.

Correlation between mitotic count and Ki-67 index. Spearman's rank correlation coefficient r=0.827 (p＜0.001).

Table 1.

Comparison of Clinical Characteristics and Recurrence Rate between Group 1 and 2

	Group 1 (n=19)	Group 2 (n=13)	p-value
Age (yr)	56.1±12.9	55.2±14.4	0.970
Sex (male: female)	14: 5	5: 8	0.289
Weight (kg)	63.4±10.6	60.7±10.2	0.152
Height (m)	1.64±0.07	1.64±0.08	0.318
BMI (kg/m²)	22.5±3.9	22.0±2.9	0.443
Size (cm)	6.00±4.9	7.07±4.8	0.520
Mitotic index	3.58±1.8	21.75±21.0	＜0.001 ^a
Recurrence	1 (5.3)	5 (38.5)	0.029
NIH classification			0.051
Very low risk	3 (15.8)	1 (7.7)
Low risk	8 (42.1)	1 (7.7)
Intermediate risk	7 (36.8)	7 (53.8)
High risk	1 (5.3)	4 (30.8)

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

Group 1, Ki-67 index ≤5%; Group 2, Ki-67 index ＞5%.

NIH, National Institutes of Health.

^a Statistically significant.

Table 2.

Multivariate Linear Regression of Variables Associated with Ki-67 Index

Variable	OR	95% CI	p-value
Size	0.968	–0.178–0.352	0.342
Mitotic index	4.096	–0.96–0.262	＜0.001
Age	–0.441	–0.88–0.87	0.663

F=8.652, R²=0.49, adjusted R²=0.43, and p＜0.001.

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ORCID iDs: You Sun Kim
https://orcid.org/http://orcid.org/0000-0002-5156-3458
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