Prognostic Significance of Ki-67 Expression in Rectal Carcinoid Tumors

Su Min Hong; You Sun Kim; Jung Seop Moon; Jin Nam Kim; Myoung Ki Oh; Sun Ok Kwon; Seong Yeon Jeong; Seong Woo Hong; Yun Kyung Kang

doi:10.4166/kjg.2013.61.2.82

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Hong, Kim, Moon, Kim, Oh, Kwon, Jeong, Hong, and Kang: Prognostic Significance of Ki-67 Expression in Rectal Carcinoid Tumors

Original Article

Korean J Gastroenterol 2013;61(2):82-87.

Published online: 4 October 2013

DOI: https://doi.org/10.4166/kjg.2013.61.2.82

Prognostic Significance of Ki-67 Expression in Rectal Carcinoid Tumors

Su Min Hong, You Sun Kim, Jung Seop Moon, Jin Nam Kim, Myoung Ki Oh, Sun Ok Kwon, Seong Yeon Jeong, 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, Inje University Seoul Paik Hospital, 9 Mareunnae-ro, Jung-gu, Seoul 100-032, Korea. Tel: +82-2-2270-0015, Fax: +82-2-2270-0579, E-mail: yousunk69@korea.com

Received 6 August 201218 October 2012 Accepted 23 October 2012

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

Rectal carcinoid tumors can be resected with endoscopy, and it is important to assess their prognostic factors. We evaluated the potential of Ki-67 expression as a prognostic factor in rectal carcinoid tumors.

Methods

We retrospectively reviewed the medical records of 37 patients with rectal carcinoid tumors who got endoscopic resection from January 2001 to January 2011 at Inje University Seoul Paik Hospital. We analyzed their endoscopic and histologic findings, Ki-67 expression, clinical outcome, and prognosis.

Results

The mean age (±SD) of the patients was 56.3±10.7 years, and the male: female ratio was 3.6：1. The mean tumor size was 0.5±0.4 cm, 33 patients showed grade 1 tumors (89.2%) and the average Ki-67 expression was 0.7±1.2%. Thirty five patients underwent endoscopic mucosal resection, and two required endoscopic submucosal dissection. Eight patients had positive margins after resection, but no cases of lymphovascular invasion were identified. The median follow-up duration was 21.4±25.4 months, and no recurrences were observed.

Conclusions

In low grade rectal carcinoid tumors which are lack of central depression on colonoscopy, the expression of a molecular marker of malignant potential, Ki-67, was low. Therefore, endoscopic resection seemed to be a safe and effective treatment for these tumors.

Keywords: Rectum, Carcinoid tumor, Ki-67, Endoscopy, Therapeutics

References

1. Jensen RT. Endocrine tumors of the gastrointestinal tract and pancreas. Longo D, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J, editors. Harrison's principles of internal medicine. Volume 2. 18th ed.New York: McGraw Hill;2011. p. 3056–3065.

2. Pinchot SN, Holen K, Sippel RS, Chen H. Carcinoid tumors. Oncologist. 2008; 13:1255–1269.

3. Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD. Current status of gastrointestinal carcinoids. Gastroenterology. 2005; 128:1717–1751.

4. Sun JM, Jung HC. Gastrointestinal carcinoid tumor. Korean J Gastroenterol. 2004; 44:59–65.

5. Soga J. Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914 reported cases. Cancer. 2005; 103:1587–1595.

6. Mashimo Y, Matsuda T, Uraoka T, et al. Endoscopic submucosal resection with a ligation device is an effective and safe treatment for carcinoid tumors in the lower rectum. J Gastroenterol Hepatol. 2008; 23:218–221.

7. Kinoshita T, Kanehira E, Omura K, Tomori T, Yamada H. Transanal endoscopic microsurgery in the treatment of rectal carcinoid tumor. Surg Endosc. 2007; 21:970–974.

8. Lin MX, Wen ZF, Feng ZY, He D. Expression and significance of Bmi-1 and Ki67 in colorectal carcinoma tissues. Ai Zheng. 2008; 27:1321–1326.

9. Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. 2010; 39:707–712.

10. Bosman F, Carneiro F, Hruban R, Theise N. WHO classification of tumours of the digestive system. Lyon, France: IARC Press;2010.

11. McCormick D, Yu C, Hobbs C, Hall PA. The relevance of antibody concentration to the immunohistological quantification of cell proliferation-associated antigens. Histopathology. 1993; 22:543–547.

12. Modlin IM, Sandor A. An analysis of 8305 cases of carcinoid tumors. Cancer. 1997; 79:813–829.

13. Kobayashi K, Katsumata T, Yoshizawa S, et al. Indications of endoscopic polypectomy for rectal carcinoid tumors and clinical usefulness of endoscopic ultrasonography. Dis Colon Rectum. 2005; 48:285–291.

14. Okamoto Y, Fujii M, Tateiwa S, et al. Treatment of multiple rectal carcinoids by endoscopic mucosal resection using a device for esophageal variceal ligation. Endoscopy. 2004; 36:469–470.

15. Ahmad NA, Kochman ML, Long WB, Furth EE, Ginsberg GG. Efficacy, safety, and clinical outcomes of endoscopic mucosal resection: a study of 101 cases. Gastrointest Endosc. 2002; 55:390–396.

16. Moon SH, Hwang JH, Sohn DK, et al. Endoscopic submucosal dissection for rectal neuroendocrine (carcinoid) tumors. J Laparoendosc Adv Surg Tech A. 2011; 21:695–699.

17. Park HW, Byeon JS, Park YS, et al. Endoscopic submucosal dissection for treatment of rectal carcinoid tumors. Gastrointest Endosc. 2010; 72:143–149.

18. Glancy DG, Pullyblank AM, Thomas MG. The role of colonoscopic endoanal ultrasound scanning (EUS) in selecting patients suitable for resection by transanal endoscopic microsurgery (TEM). Colorectal Dis. 2005; 7:148–150.

19. Costes V, Marty-Ané C, Picot MC, et al. Typical and atypical bron-chopulmonary carcinoid tumors: a clinicopathologic and KI-67- labeling study. Hum Pathol. 1995; 26:740–745.

20. Moyana TN, Xiang J, Senthilselvan A, Kulaga A. The spectrum of neuroendocrine differentiation among gastrointestinal carcinoids: importance of histologic grading, MIB-1, p53, and bcl-2 immunoreactivity. Arch Pathol Lab Med. 2000; 124:570–576.

21. Sökmensüer C, Gedikoglu G, Uzunalimoglu B. Importance of proliferation markers in gastrointestinal carcinoid tumors: a clinicopathologic study. Hepatogastroenterology. 2001; 48:720–723.

22. Shimizu T, Tanaka S, Haruma K, et al. Growth characteristics of rectal carcinoid tumors. Oncology. 2000; 59:229–237.

23. Hotta K, Shimoda T, Nakanishi Y, Saito D. Usefulness of Ki-67 for predicting the metastatic potential of rectal carcinoids. Pathol Int. 2006; 56:591–596.

24. Kawahara M, Kammori M, Kanauchi H, et al. Immunohistochemical prognostic indicators of gastrointestinal carcinoid tumours. Eur J Surg Oncol. 2002; 28:140–146.

Fig. 1.

(A) Endoscopic findings. Colonoscopy showed a 0.6 cm sized mild yellowish elevated lesion with intact mucosa at anal verge 7.0 cm site. (B) EUS findings. EUS showed a 0.7×0.6 cm sized hypoechoic lesion in the submucosal layer of the rectum.

Fig. 2.

Ki-67 staining in tumors resected by endoscopic mucosal resection (×200). On light microscopic examination, moderately uniform, small, round tumor cells with minimal cellular atypia were seen. The arrows indicate Ki-67 labeled nuclei, and the Ki-67 labeling index was 4% in this sample.

Table 1.

Grading of Gastroenteropancreatic NET according to Proliferative Activity by WHO Classification

Grade	Criteria
G1 (low grade)	＜2 mitoses/10 HPF and ＜3% Ki-67 index
G2 (intermediate grade)	2–20 mitoses/10 HPF or 3–20% Ki-67 index
G3 (high grade)	＞20 mitoses/10 HPF or ＞20% Ki-67 index

NET, neuroendocrine tumor; WHO, World Health Organization; G, grade.

Table 2.

Baseline Characteristics of Patients and Tumors

Parameter	Data
Age (yr)	56.3±10.7
Gender
Male	29 (78.4)
Female	8 (21.6)
Tumor size (cm)	0.5±0.4
Mean follow-up (month)	21.4±25.4
Involvement of resection margin
Yes	8 (21.6)
No	29 (78.4)
WHO classification
G1	33 (89.2)
G2	4 (10.8)
G3	0 (0)
Ki-67 expression (%)
＜0.7	29 (78.4)
≥0.7	8 (21.6)

Values are presented as mean±SD or n (%). WHO, World Health Organization; G, grade.

Table 3.

Comparative Results of Ki-67 Expression with Size, Age, Gender and Involvement of Resection Margin

Variable	Mean Ki-67 (%) p-value
Tumor size (cm)
＜1	0.7
≥1.0 and ≤1.5	0.8 0.785
Age (yr)
≤55	0.7 0.880
＞55	0.7
Gender
Male	0.7
Female	0.8 0.771
Involvement of resection margin
Positive	0.4
Negative	0.8 0.498

p＜0.05 accepted as statistically significant.

Table 4.

Correlation of WHO Classification Grade with Size, Age, Gender and Involvement of Resection Margin

Variable	G1 (n=33)	G2 (n=4)	p-value
Tumor size (cm)	0.5±0.4	0.6±0.4	0.776
Age (yr)	56.6±10.5	53.5±13.2	0.589
Gender
Male	26/33 (78.8)	3/4 (75.0)	0.867
Resection margin
Positive	8/33 (24.2)	0/4 (0.0)	0.279

Values are presented as mean±SD or n (%). p＜0.05 accepted as statistically significant. WHO, World Health Organization; G, grade.

Table 5.

Correlation of Ki-67 Expression with Size, Age, Gender and Involvement of Resection Margin

	Ki-67 ＜0.7% (n=29)	Ki-67 ≥0.7%(n=8)	% p-value
Tumor size (cm)	0.5±0.4	0.4±0.3	0.460
Age (yr)	56.1±10.5	56.8±12.0	0.888
Gender
Male	22/29 (75.9)	7/8 (87.5)	0.493
Resection margin
Positive	6/29 (20.7)	2/8 (25.0)	0.800

Values are presented as mean±SD or n (%). p＜0.05 accepted as statistically significant.

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