Volume 121, Issue 6, Pages 1407-1416 (December 2001) The role of mutant Apc in the development of dysplasia and cancer in the mouse model of dextran sulfate sodium–induced colitis  Harry S. Cooper, Lynette Everley, Wen–Chi Chang, Gordon Pfeiffer, Bryan Lee, Sreekant Murthy, Margie L. Clapper  Gastroenterology  Volume 121, Issue 6, Pages 1407-1416 (December 2001) DOI: 10.1053/gast.2001.29609 Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 1 Overview of study design. Gastroenterology 2001 121, 1407-1416DOI: (10.1053/gast.2001.29609) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 2 (A) Low-power H&E view of polypoid dysplasia before laser capture microdissection. Dysplastic areas (solid arrows) and nondysplastic areas (open arrows). (B) Low-power view of A after laser capture microdissection. Note that dysplastic areas (solid arrows) are captured, and non-neoplastic mucosa (open arrows) remains behind. Gastroenterology 2001 121, 1407-1416DOI: (10.1053/gast.2001.29609) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 3 (A) Percentage of mice with dysplasia and cancer. (B) Mean number of dysplasias/mouse and cancers/mouse. Min-DSS-1 cycle vs. Min-DSS-2 cycles total dysplastic lesions (P = 0.030). Min-DSS-1 cycle vs. Min-81 days total dysplastic lesions (P < 0.0002). Min-DSS-2 cycles vs. Min-102 days total dysplastic lesions (P < 0.0001). Min-DSS-1 cycle vs. WT-DSS-1 cycle total dysplastic lesions (P < 0.0001). Min-DSS-2 cycles vs. WT-DSS-2 cycles total dysplastic lesions (P < 0.0001). Gastroenterology 2001 121, 1407-1416DOI: (10.1053/gast.2001.29609) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 4 Total numbers and types of dysplasia. Min-DSS-1 cycle, flat vs. polypoid dysplasia, P = 0.016; Min-DSS-2 cycles, flat vs. polypoid dysplasia, P = 0.19; Min-81 day flat vs. polypoid dysplasia, P = 0.50; Min-102 day, flat vs. polypoid dysplasia; P = 0.016; Min-DSS-1 cycle polypoid vs. Min-DSS-2 cycles polypoid, P = 0.004; Min-DSS-1 cycle flat vs. Min-DSS-2 cycles flat, P = 0.35. Gastroenterology 2001 121, 1407-1416DOI: (10.1053/gast.2001.29609) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 5 Segment of distal colorectum and portion of mid colon from Min-DSS. There are 13 gross polypoid lesions (arrows pointing to 5 of the lesions). Non–DSS-treated Min develop on the average only 1–2 lesions per entire colorectum. Gastroenterology 2001 121, 1407-1416DOI: (10.1053/gast.2001.29609) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 6 (A) Polypoid dysplasia from Min-DSS. The dysplasia projects above the surface like a polyp. Compare with flat dysplasia in Figures 7 and 8. (B) High-power view of A, showing dysplastic epithelial cells. Gastroenterology 2001 121, 1407-1416DOI: (10.1053/gast.2001.29609) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 7 Medium-power view of flat dysplasia in Min-DSS. The dysplasia grows in a flat pattern, consists of approximately 10 crypts (arrows), and is focal. Compare with Figures 6 and 8. Gastroenterology 2001 121, 1407-1416DOI: (10.1053/gast.2001.29609) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 8 Low-power view of flat dysplasia in Min-DSS. The entire length of mucosa is replaced by dysplasia growing in a carpetlike fashion. Compare with the focal lesion in Figure 7 and polypoid lesion in Figure 6. Gastroenterology 2001 121, 1407-1416DOI: (10.1053/gast.2001.29609) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 9 Low-power view of carcinoma in polypoid lesion—Min-DSS. The carcinoma invades through the muscularis mucosae into the submucosa (solid arrow). The invasive cancer is arising from (incontinuity with) intramucosal high-grade dysplasia (open arrow). Gastroenterology 2001 121, 1407-1416DOI: (10.1053/gast.2001.29609) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 10 Polymerase chain reaction assay for LOH of Apc. Lanes 1, 3, 5, and 7 are bands before HindIII digestion (155 bp); lanes 3, 4, 7, and 8 are from nondysplastic mucosa; and lanes 1, 2, 5, and 6 are from dysplasia. After HindIII digestion, nondysplastic mucosa (lanes 4 and 8) show 2 bands, 144 bp (mutant Apc) and 123 bp (WT Apc); dysplastic lesions (lanes 2 and 6) show loss of WT Apc with only a single mutant Apc band (144 bp) remaining. Gastroenterology 2001 121, 1407-1416DOI: (10.1053/gast.2001.29609) Copyright © 2001 American Gastroenterological Association Terms and Conditions