Stereomicroscopic features of colitis‑associated tumors in mice: Evaluation of pit pattern

Yamauchi,Ryosuke; Kominato,Ken; Mitsuyama,Keiichi; Takedatsu,Hidetoshi; Yoshioka,Shinichiro; Kuwaki,Kotaro; Yamasaki,Hiroshi; Fukunaga,Shuhei; Mori,Atsushi; Akiba,Jun; Tsuruta,Osamu; Torimura,Takuji

doi:10.3892/ol.2017.6645

Stereomicroscopic features of colitis‑associated tumors in mice: Evaluation of pit pattern

Authors:
- Ryosuke Yamauchi
- Ken Kominato
- Keiichi Mitsuyama
- Hidetoshi Takedatsu
- Shinichiro Yoshioka
- Kotaro Kuwaki
- Hiroshi Yamasaki
- Shuhei Fukunaga
- Atsushi Mori
- Jun Akiba
- Osamu Tsuruta
- Takuji Torimura
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Affiliations: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Fukuoka 830‑0011, Japan
Published online on: July 21, 2017 https://doi.org/10.3892/ol.2017.6645
Pages: 3675-3682

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Abstract

Patients with longstanding ulcerative colitis have an increased risk of colorectal cancer. Mouse models for colitis‑associated tumors are indispensable for the development of novel strategies for prevention and intervention, as well as an improved understanding of the mechanisms underlying tumor formation. The present study examined whether stereomicroscopic observations with dye‑application were able to detect and discriminate tumors in a colitis‑associated tumor model in mice. Colonic tumors were induced in C57BL/6 mice by 15 cycles of treatment with dextran sulfate sodium (DSS) in drinking water. The mice were then divided into 4 groups: normal mice fed a control diet, normal mice fed an iron‑supplemented diet, 0.7% DSS mice fed an iron diet and 1.5% DSS mice fed an iron diet. The entire colons were characterized with respect to both morphology and histology. The pit pattern architecture was analyzed using stereomicroscopy with dye agents (0.2% indigo carmine or 0.06% crystal violet). The tumor histology was graded as negative, indefinite or positive for dysplasia. The positive category was divided into two subcategories: low‑grade dysplasia (LGD) and high‑grade dysplasia (HGD). The tumor incidences and multiplicity were signiﬁcantly higher in mice fed an iron diet and 1.5% DSS compared with in mice fed an iron diet and 0.7% DSS. Compared with LGD, HGD was predominantly located in the distal colon, was larger in size and had a higher incidence of elevated lesions (Is and IIa) and a lower incidence of flat lesions (IIb). In regards to the pit pattern, HGD had a high incidence of VI pits and a low incidence of IV, IIIL and II pits. In conclusion, evaluation of the pit pattern using stereomicroscopy with dye‑application is useful for detecting and discriminating neoplastic changes in DSS mice and may further our understanding of the mechanisms that induce tumor formation in patients with ulcerative colitis and the characterization of pharmaceutical responses.

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1	Strober W, Fuss I and Mannon P: The fundamental basis of inflammatory bowel disease. J Clin Invest. 117:514–521. 2007. View Article : Google Scholar : PubMed/NCBI
2	Eaden JA, Abrams KR and Mayberry JF: The risk of colorectal cancer in ulcerative colitis: A meta-analysis. Gut. 48:526–535. 2001. View Article : Google Scholar : PubMed/NCBI
3	Ullman TA and Itzkowitz SH: Intestinal inflammation and cancer. Gastroenterology. 140:1807–1816. 2011. View Article : Google Scholar : PubMed/NCBI
4	Morson BC and Pang LS: Rectal biopsy as an aid to cancer control in ulcerative colitis. Gut. 8:423–434. 1967. View Article : Google Scholar : PubMed/NCBI
5	Bernstein CN, Shanahan F and Weinstein WM: Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis? Lancet. 343:71–74. 1994. View Article : Google Scholar : PubMed/NCBI
6	Blackstone MO, Riddell RH, Rogers BH and Levin B: Dysplasia-associated lesion or mass (DALM) detected by colonoscopy in long-standing ulcerative colitis: An indication for colectomy. Gastroenterology. 80:366–374. 1981.PubMed/NCBI
7	Basu S, Torigian D and Alavi A: The role of modern molecular imaging techniques in gastroenterology. Gastroenterology. 135:1055–1061. 2008. View Article : Google Scholar : PubMed/NCBI
8	Axelrad AM, Fleischer DE, Geller AJ, Nguyen CC, Lewis JH, Al-Kawas FH, Avigan MI, Montgomery EA and Benjamin SB: High-resolution chromoendoscopy for the diagnosis of diminutive colon polyps: Implications for colon cancer screening. Gastroenterology. 110:1253–1258. 1996. View Article : Google Scholar : PubMed/NCBI
9	Fu KI, Sano Y, Kato S, Fujii T, Nagashima F, Yoshino T, Okuno T, Yoshida S and Fujimori T: Chromoendoscopy using indigo carmine dye spraying with magnifying observation is the most reliable method for differential diagnosis between non-neoplastic and neoplastic colorectal lesions: A prospective study. Endoscopy. 36:1089–1093. 2004. View Article : Google Scholar : PubMed/NCBI
10	Yoshioka S, Mitsuyama K, Takedatsu H, Kuwaki K, Yamauchi R, Yamasaki H, Fukunaga S, Akiba J, Kinugasa T, Akagi Y, et al: Advanced endoscopic features of ulcerative colitis-associated neoplasias: Quantification of autofluorescence imaging. Int J Oncol. 48:551–558. 2016.PubMed/NCBI
11	Watanabe T, Ajioka Y, Mitsuyama K, Watanabe K, Hanai H, Nakase H, Kunisaki R, Matsuda K, Iwakiri R, Hida N, et al: Comparison of targeted vs random biopsies for surveillance of ulcerative colitis-associated colorectal cancer. Gastroenterology. 151:1122–1130. 2016. View Article : Google Scholar : PubMed/NCBI
12	Sada M, Igarashi M, Yoshizawa S, Kobayashi K, Katsumata T, Saigenji K, Otani Y, Okayasu I and Mitomi H: Dye spraying and magnifying endoscopy for dysplasia and cancer surveillance in ulcerative colitis. Dis Colon Rectum. 47:1816–1823. 2004. View Article : Google Scholar : PubMed/NCBI
13	Hata K, Watanabe T, Kazama S, Suzuki K, Shinozaki M, Yokoyama T, Matsuda K, Muto T and Nagawa H: Earlier surveillance colonoscopy programme improves survival in patients with ulcerative colitis associated colorectal cancer: Results of a 23-year surveillance programme in the Japanese population. Br J Cancer. 89:1232–1236. 2003. View Article : Google Scholar : PubMed/NCBI
14	Matsumoto T, Nakamura S, Jo Y, Yao T and Iida M: Chromoscopy might improve diagnostic accuracy in cancer surveillance for ulcerative colitis. Am J Gastroenterol. 98:1827–1833. 2003. View Article : Google Scholar : PubMed/NCBI
15	Kiesslich R, Goetz M, Lammersdorf K, Schneider C, Burg J, Stolte M, Vieth M, Nafe B, Galle PR and Neurath MF: Chromoscopy-guided endomicroscopy increases the diagnostic yield of intraepithelial neoplasia in ulcerative colitis. Gastroenterology. 132:874–882. 2007. View Article : Google Scholar : PubMed/NCBI
16	Kiesslich R, Fritsch J, Holtmann M, Koehler HH, Stolte M, Kanzler S, Nafe B, Jung M, Galle PR and Neurath MF: Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis. Gastroenterology. 124:880–888. 2003. View Article : Google Scholar : PubMed/NCBI
17	Kiesler P, Fuss IJ and Strober W: Experimental models of inflammatory bowel diseases. Cell Mol Gastroenterol Hepatol. 1:154–170. 2015. View Article : Google Scholar : PubMed/NCBI
18	Kanneganti M, Mino Kenudson M and Mizoguchi E: Animal models of colitis-associated carcinogenesis. J Biomed Biotechnol. 2011:3426372011. View Article : Google Scholar : PubMed/NCBI
19	Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y and Nakaya R: A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 98:694–702. 1990. View Article : Google Scholar : PubMed/NCBI
20	Okayasu I, Yamada M, Mikami T, Yoshida T, Kanno J and Ohkusa T: Dysplasia and carcinoma development in a repeated dextran sulfate sodium-induced colitis model. J Gastroenterol Hepatol. 17:1078–1083. 2002. View Article : Google Scholar : PubMed/NCBI
21	Committee for the Update of the Guide for the Care and Use of Laboratory A and National Research Council: Guide for the Care and Use of Laboratory Animals. 8th. National Academies Press; Washington, DC: 2011
22	Seril DN, Liao J, Yang CS and Yang GY: Systemic iron supplementation replenishes iron stores without enhancing colon carcinogenesis in murine models of ulcerative colitis: Comparison with iron-enriched diet. Dig Dis Sci. 50:696–707. 2005. View Article : Google Scholar : PubMed/NCBI
23	Liao J, Seril DN, Yang AL, Lu GG and Yang GY: Inhibition of chronic ulcerative colitis associated adenocarcinoma development in mice by inositol compounds. Carcinogenesis. 28:446–454. 2007. View Article : Google Scholar : PubMed/NCBI
24	Tardif SD, Coleman K, Hobbs TR and Lutz C: IACUC review of nonhuman primate research. ILAR J. 54:234–245. 2013. View Article : Google Scholar : PubMed/NCBI
25	Cooper HS, Murthy SN, Shah RS and Sedergran DJ: Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 69:238–249. 1993.PubMed/NCBI
26	Takaki K, Mitsuyama K, Tsuruta O, Toyonaga A and Sata M: Attenuation of experimental colonic injury by thiazolidinedione agents. Inflamm Res. 55:10–15. 2006. View Article : Google Scholar : PubMed/NCBI
27	Dieleman LA, Ridwan BU, Tennyson GS, Beagley KW, Bucy RP and Elson CO: Dextran sulfate sodium-induced colitis occurs in severe combined immunodeficient mice. Gastroenterology. 107:1643–1652. 1994. View Article : Google Scholar : PubMed/NCBI
28	The Paris endoscopic classification of superficial neoplastic lesions: Esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc. 58:(6 Suppl). 3–43. 2003. View Article : Google Scholar
29	Hata K, Watanabe T, Shinozaki M, Kojima T and Nagawa H: To dye or not to dye? That is beyond question! Optimising surveillance colonoscopy is indispensable for detecting dysplasia in ulcerative colitis. Gut. 53:17222004.PubMed/NCBI
30	Kudo S, Hirota S, Nakajima T, Hosobe S, Kusaka H, Kobayashi T, Himori M and Yagyuu A: Colorectal tumours and pit pattern. J Clin Pathol. 47:880–885. 1994. View Article : Google Scholar : PubMed/NCBI
31	Kudo S, Tamura S, Nakajima T, Yamano H, Kusaka H and Watanabe H: Diagnosis of colorectal tumorous lesions by magnifying endoscopy. Gastrointest Endosc. 44:8–14. 1996. View Article : Google Scholar : PubMed/NCBI
32	Riddell RH, Goldman H, Ransohoff DF, Appelman HD, Fenoglio CM, Haggitt RC, Ahren C, Correa P, Hamilton SR, Morson BC, et al: Dysplasia in inflammatory bowel disease: Standardized classification with provisional clinical applications. Hum Pathol. 14:931–968. 1983. View Article : Google Scholar : PubMed/NCBI
33	Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, Dixon MF, Fenoglio-Preiser CM, Fléjou JF, Geboes K, et al: The Vienna classification of gastrointestinal epithelial neoplasia. Gut. 47:251–255. 2000. View Article : Google Scholar : PubMed/NCBI
34	Barral M, Dohan A, Allez M, Boudiaf M, Camus M, Laurent V, Hoeffel C and Soyer P: Gastrointestinal cancers in inflammatory bowel disease: An update with emphasis on imaging findings. Crit Rev Oncol Hematol. 97:30–46. 2016. View Article : Google Scholar : PubMed/NCBI
35	Matkowskyj KA, Chen ZE, Rao MS and Yang GY: Dysplastic lesions in inflammatory bowel disease: Molecular pathogenesis to morphology. Arch Pathol Lab Med. 137:338–350. 2013. View Article : Google Scholar : PubMed/NCBI
36	Becker C, Fantini MC, Wirtz S, Nikolaev A, Kiesslich R, Lehr HA, Galle PR and Neurath MF: In vivo imaging of colitis and colon cancer development in mice using high resolution chromoendoscopy. Gut. 54:950–954. 2005. View Article : Google Scholar : PubMed/NCBI