MIB-1 labeling index, Ki-67, is an indicator of invasive intraductal papillary mucinous neoplasm

Shimura,Tatsuo; Kofunato,Yasuhide; Okada,Ryo; Yashima,Rei; Okada,Koji; Araki,Kenichiro; Hosouchi,Yasuo; Kuwano,Hiroyuki; Takenoshita,Seiichi

doi:10.3892/mco.2016.908

MIB-1 labeling index, Ki-67, is an indicator of invasive intraductal papillary mucinous neoplasm

Authors:
- Tatsuo Shimura
- Yasuhide Kofunato
- Ryo Okada
- Rei Yashima
- Koji Okada
- Kenichiro Araki
- Yasuo Hosouchi
- Hiroyuki Kuwano
- Seiichi Takenoshita
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Affiliations: Department of Cancer Biology and Electronics, Fukushima Medical University, Fukushima 960‑1295, Japan, Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960‑1295, Japan, Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma 371‑8511, Japan, Department of Surgery and Laparoscopic Surgery, Gunma Prefecture Saiseikai‑Maebashi Hospital, Maebashi, Gunma 371‑0821, Japan
Published online on: May 20, 2016 https://doi.org/10.3892/mco.2016.908
Pages: 317-322

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Abstract

Despite strict criteria for the observation of intraductal papillary mucinous neoplasm (IPMN), it remains difficult to distinguish invasive IPMN from non-invasive IPMN. The aim of the present study was to identify an indicator of invasive IPMN. The present study retrospectively evaluated 53 patients (28 with non‑invasive and 25 with invasive IPMN) who underwent resection of IPMN, and examined the usefulness of the MIB‑1 labeling index as an indicator of invasive IPMN. The MIB‑1 labeling indexes in patients with invasive IPMN were significantly higher compared with those with non‑invasive IPMN (P<0.001). A receiver operating characteristic curve revealed that the area under the curve was 0.822. These results suggested that a cut‑off level for the MIB‑1 labeling index should be set to 15.5% to distinguish invasive from non‑invasive IPMN. A multivariate analysis using a logistic regression model revealed the MIB‑1 labeling index (hazard ratio, 18.692; 95% confidential interval, 4.171‑83.760; P<0.001) and the existence of mural nodules (hazard ratio, 6.187, 95% confidential interval, 1.039‑36.861; P=0.045) were predictive factors for invasive IPMN. However, no statistically significant differences were observed between patients with a lower MIB-1 labeling index and patients with a higher MIB‑1 labeling index (P=0.798). The MIB-1 labeling index must be considered as a candidate for the classification of IPMN.

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1	Ohashi K, Murakami Y, Maruyama M, Takekoshi T, Ohta H, Ohhashi I, Takagi K and Kato K: Four cases of mucous secreting pancreatic cancer. Prog Dig Endosc. 20:348–351. 1982.
2	Werner J, Fritz S and Büchler MW: Intraductal papillary mucinous neoplasms of the pancreas-a surgical disease. Nat Rev Gastroenterol Hepatol. 9:253–259. 2012. View Article : Google Scholar : PubMed/NCBI
3	Tanaka M, Chari S, Adsay V, Fernandez-del Castillo C, Falconi M, Shimizu M, Yamaguchi K, Yamao K and Matsuno S: International Association of Pancreatology: International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology. 6:17–32. 2006. View Article : Google Scholar : PubMed/NCBI
4	Tanaka M, del Fernández Castillo C, Adsay V, Chari S, Falconi M, Jang JY, Kimura W, Levy P, Pitman MB, Schmidt CM, et al: International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 12:183–197. 2012. View Article : Google Scholar : PubMed/NCBI
5	Salvia R, Fernández-del Castillo C, Bassi C, Thayer SP, Falconi M, Mantovani W, Pederzoli P and Warshaw AL: Main-duct intraductal papillary mucinous neoplasms of the pancreas: Clinical predictors of malignancy and long-term survival following resection. Ann Surg. 239:678–685; discussion 685–687. 2004. View Article : Google Scholar : PubMed/NCBI
6	Roch AM, Ceppa EP, Al-Haddad MA, DeWitt JM, House MG, Zyromski NJ, Nakeeb A and Schmidt CM: The natural history of main duct-involved, mixed-type intraductal papillary mucinous neoplasms: Parameters predictive of progression. Ann Surg. 260:680–688; discussion 688–690. 2014. View Article : Google Scholar : PubMed/NCBI
7	Sugiyama M, Izumisato Y, Abe N, Masaki T, Mori T and Atomi Y: Predictive factors for malignancy in intraductal papillary-mucinous tumors of the pancreas. Br J Surg. 90:1244–1249. 2003. View Article : Google Scholar : PubMed/NCBI
8	Fritz S, Hackert T, Hinz U, Hartwig W, Büchler MW and Werner J: Role of serum carbohydrate antigen 19-9 and carcinoembryonic antigen in distinguishing between benign and invasive intraductal papillary mucinous neoplasm of the pancreas. Br J Surg. 98:104–110. 2011. View Article : Google Scholar : PubMed/NCBI
9	Kang MJ, Jang JY, Kim SJ, Lee KB, Ryu JK, Kim YT, Yoon YB and Kim SW: Cyst growth rate predicts malignancy in patients with branch duct intraductal papillary mucinous neoplasms. Clin Gastroenterol Hepatol. 9:87–93. 2011. View Article : Google Scholar : PubMed/NCBI
10	He J, Cameron JL, Ahuja N, Makary MA, Hirose K, Choti MA, Schulick RD, Hruban RH, Pawlik TM and Wolfgang CL: Is it necessary to follow patients after resection of a benign pancreatic intraductal papillary mucinous neoplasm? J Am Coll Surg. 216:657–665; discussion 665–667. 2013. View Article : Google Scholar : PubMed/NCBI
11	Fritz S, Schirren M, Klauss M, Bergmann F, Hackert T, Hartwig W, Strobel O, Grenacher L, Büchler MW and Werner J: Clinicopathologic characteristics of patients with resected multifocal intraductal papillary mucinous neoplasm of the pancreas. Surgery. 152(3 Suppl 1): S74–S80. 2012. View Article : Google Scholar : PubMed/NCBI
12	Sturm EC, Roch AM, Shaffer KM, Schmidt CM II, Lee SJ, Zyromski NJ, Pitt HA, Dewitt JM, Al-Haddad MA, Waters JA and Schmidt CM: Obesity increases malignant risk in patients with branch-duct intraductal papillary mucinous neoplasm. Surgery. 154:803–808; discussion 808–809. 2013. View Article : Google Scholar : PubMed/NCBI
13	Tang LH, Gonen M, Hedvat C, Modlin IM and Klimstra DS: Objective quantification of the Ki67 proliferative index in neuroendocrine tumors of the gastroenteropancreatic system: A comparison of digital image analysis with manual methods. Am J Surg Pathol. 36:1761–1770. 2012. View Article : Google Scholar : PubMed/NCBI
14	Viale G, Giobbie-Hurder A, Regan MM, Coates AS, Mastropasqua MG, Dell'Orto P, Maiorano E, MacGrogan G, Braye SG, Ohlschlegel C, et al: Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: Results from Breast International Group Trial 1–98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol. 26:5569–5575. 2008. View Article : Google Scholar : PubMed/NCBI
15	Semba S, Moriya T, Kimura W and Yamakawa M: Phosphrylated Akt/PKB controls cell growth and apoptosis in intraductal papillary-mucinous tumor and invasive ductal adenocarcinoma of the pancreas. Pancreas. 26:250–257. 2003. View Article : Google Scholar : PubMed/NCBI
16	Kataoka TR, Ioka T, Tsukamoto Y, Matsumura M, Ishiguro S and Nishizawa Y: Nuclear expression of STAT5 in intraductal papillary mucinous neoplasms of the pancreas. Int J Surg Pathol. 15:277–281. 2007. View Article : Google Scholar : PubMed/NCBI
17	Okada K, Masuda N, Fukai Y, Shimura T, Nishida Y, Hosouchi Y, Kashiwabara K, Nakajima T and Kuwano H: Immunohistochemical expression of 14-3-3 sigma protein in intraductal papillary mucinous tumor and invasive ductal carcinoma of the pancreas. Anticancer Res. 26:3105–3110. 2006.PubMed/NCBI
18	Abe K, Suda K, Arakawa A, Yamasaki S, Sonoue H, Mitani K and Nobukawa B: Different patterns of p16INK4A and p53 protein expressions in intraductal papillary-mucinous neoplasms and pancreatic intraepithelial neoplasia. Pancreas. 34:85–91. 2007. View Article : Google Scholar : PubMed/NCBI
19	Okimura A, Hirano H, Nishigami T, Ueyama S, Tachibana S, Fukuda Y, Yamanegi K, Ohyama H, Terada N and Nakasho K: Immunohistochemical analysis of E cadherin, beta-catenin, CD44s, and CD44v6 expressions, and Ki-67 labeling index in intraductal papillary mucinous neoplasms of the pancreas and associated invasive carcinomas. Med Mol Morphol. 42:222–229. 2009. View Article : Google Scholar : PubMed/NCBI
20	Islam HK, Fujioka Y, Tomidokoro T, Sugiura H, Takahashi T, Kondo S and Katoh H: Immunohistochemical analysis of expression of molecular biologic factors in intraductal papillary-mucinous tumors of pancreas-diagnostic and biologic significance. Hepatogastroenterology. 46:2599–2605. 1999.PubMed/NCBI
21	Terada T, Ohta T, Kitamura Y, Ashida K and Matsunaga Y: Cell proliferative activity in intraductal papillary-mucinous neoplasms and invasive ductal adenocarcinomas of the pancreas: An immunohistochemical study. Arch Pathol Lab Med. 122:42–46. 1998.PubMed/NCBI
22	Takeshita A, Kimura W, Hirai I, Takasu N, Moriya T, Tezuka K and Watanabe T: Clinicopathologic study of the MIB-1 labeling index (Ki67) and postoperative prognosis for intraductal papillary mucinous neoplasms and ordinary ductal adenocarcinoma. Pancreas. 41:114–120. 2012. View Article : Google Scholar : PubMed/NCBI
23	Yamao K, Yanagisawa A, Takahashi K, Kimura W, Doi R, Fukushima N, Ohike N, Shimizu M, Hatori T, Nobukawa B, et al: Clinicopathological features and prognosis of mucinous cystic neoplasm with ovarian-type stroma: A multi-institutional study of the Japan pancreas society. Pancreas. 40:67–71. 2011. View Article : Google Scholar : PubMed/NCBI
24	Hirooka Y, Goto H, Itoh A, Hashimoto S, Niwa K, Ishikawa H, Okada N, Itoh T and Kawashima H: Case of intraductal papillary mucinous tumor in which endosonography-guided fine-needle aspiration biopsy caused dissemination. J Gastroenterol Hepatol. 18:1323–1324. 2003. View Article : Google Scholar : PubMed/NCBI