Abstract
Variations of Ki-67, p53, and Adnab-9 monoclonal antibody reactions in colonic adenomas may be associated with colonic cancer risk. We studied the predictive value of these markers for adverse behavior in severely dysplastic colorectal adenomas, such as an associated carcinoma, multiplicity of adenomas, and subsequent development of adenomas. For this purpose we compared the clinical, gross, and histologic characteristics of highly dysplastic index polyps in 42 patients with Ki 67, p53, and Adnab-9 immunostaining and other molecular markers. Polyps were removed endoscopically, and severely dysplastic polyps were stained immunohistochemically with Ki-67, Adnab-9, and p53 protein by the avidin biotin conjugate (ABC) technique. Quantitative DNA (QDNA) was analyzed by computer-assisted image analysis. Ki-67 immunohistochemistry showed reversal of normal distribution of nuclear staining from the normal basal position to the upper third of the colonic crypts. This abnormality of immunostaining in dysplastic adenomas was the earliest detected by the panel we used. A statistically significant correlation was seen between invasiveness of carcinoma in the index polyp and polyp size (P = 0.003), sessile morphology (P = 0.037), and villous or tubulovillous histology (P = 0.019). In the index adenoma, p53 positivity was correlated with multiplicity at initial examination (P = 0.053), villous histology (P = 0.053), invasiveness of carcinoma (P < 0.003), and recurrence of colorectal adenomas (P = 0.025). Although p53 positivity and aneuploidy were correlated with invasiveness of carcinoma in the index polyp (P = 0.025), Adnab-9 positivity was not. However, Adnab-9 positivity in the index polyp was associated with multiplicity of adenomas (P = 0.04) as well as recurrence of adenomas (P < 0.024). In conclusion, in addition to the morphologic and histologic markers already known, Ki-67, Adnab-9 antibody, and p53 protein may be prognostic indicators useful in follow-up of patients with severely dysplastic colorectal adenomas. Adnab-9 antibody may identify a field defect in above-average-risk adenoma-bearing patients.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Atkin WS, Morson BC, Cuzick J: Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med 326(10):658-662, 1992
Schatzkin A, Lanza E, Corle D, Lance P, Iber F, Caan B, Shike M, Weissfeld J, Burt R, Cooper MR, Kikendal JW, Cahill J: Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. N Engl J Med 342(16):1149-1155, 2000
Van Stolk RU, Beck GJ, Baron JA, Haile R, Summers R: Adenoma characteristics at first colonoscopy as predictors of adenoma recurrence and characteristics at follow-up. The Polyp Prevention Study Group. Gastroenterology 115(1):13-18, 1998
Levin TR, Palitz A, Grossman S, Conell C, Finkler L, Ackerson L, Rumore G, Selby JV: Predicting advanced proximal colonic neoplasia with screening sigmoidoscopy. JAMA 281(17):1611-1617, 1999
Wolley RC, Schreiber K, Koss LG, Karas M, Sherman A: DNA distribution in human colon carcinomas and its relationship to clinical behavior. J Natl Cancer Inst 69(1):15-22, 1982
Kokal W, Sheibani K, Terz J, Harada JR: Tumor DNA content in the prognosis of colorectal carcinoma. JAMA 13;255(22):3123-3127, 1986
Armitage NC, Robins RA, Evans DF, Turner DR, Baldwin RW, Hardcastle JD: The influence of tumour cell DNA abnormalities on survival in colorectal cancer. Br J Surg 72(10):828-830, 1985
Tobi M, Maliakkal BJ, Zitron I, Alousi M, Goo R, Nochomovitz L, Luk G: Adenoma-derived antibody, Adnab-9 recognizes a membrane-bound glycoprotein in colonic tissue and effluent material from patients with colorectal neoplasia. Cancer Lett 30:67(1):61-69, 1992
Tobi M, Kaila V, Hassan N, Gallinger S, Fligiel S, Hatfield J, Gesell M, SokrW, Luk G, Odze RD: Monoclonal antibody Adnab-9 defines a preneoplastic marker in epithelium at risk for adenocarcinoma of the small intestine. Hum Pathol 30(4):467-473, 1999
Tobi M, Darmon E, Phillips T, Heller T, Rozen P, Nochomovitz L, SteinbergW: Increased expression of a putative adenoma-associated antigen in precolonoscopic effluent of patients with colorectal cancer. Cancer Lett 15;51(1):21-25, 1990
Tobi M, Kaila V, Goo R, Kinzie J, Ehrinpreis M, Maliakkal BJ: An adenoma-associated antigen as a preneoplastic marker in familial polyposis coli versus sporadic colonic neoplasia. Gastroenterology 102:A403, (abstract) 1992
van den Berg FM, Tigges AJ, Schipper ME, den Hartog-Jager FC, Kroes WG, Walboomers JM: Expression of the nuclear oncogene p53 in colon tumors. J Pathol 157(3):193-199, 1989
Ahnen DJ, Feigl P, Quan G, Fenoglio-Preiser C, Lovato LC, Bunn PA Jr, Stemmerman G, Wells JD, Macdonald JS, Meyskens FL Jr: Kiras mutation and p53 overexpression predict the clinical behavior of colorectal cancer: a Southwest Oncology Group study. Cancer Res 15;58(6):1149-1158, 1998
Wong AJ, Kohn GJ, Schwartz HJ, Ruebner BH, Lawson MJ: Colorectal cancer and noncancer patients have similar labeling indices by microscopy and computed image analysis. Hum Pathol 26(12):1329-1332, 1995
Lawson MJ, White LM, Coyle P, Bulter RN, Roberts-Thomson IC, Conyers RA: An assessment of proliferative and enzyme activity in transitional mucosa adjacent to colonic cancer. Cancer 64(5):1061-1066, 1989
Kim EC, Lance P: Colorectal polyps and their relationship to cancer. Gastroenterol Clin North Am 26(1):1-17, 1997
Cooper HS: Surgical pathology of endoscopically removed malignant polyps of the colon and rectum. AmJ Surg Pathol 7(7):613-623, 1983
Wolff WI, Shinya H: Definitive treatment of “malignant” polyps of the colon. Ann Surg 182(4):516-525, 1975
Hsu SM, Raine L, Fanger H: Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29(4):577-580, 1981
Teplitz RL, Joyce JE, Doroshov SI, Min BH: A preliminary ploidy analysis of diploid and triploid salmonids. Can J Fish Aquat Sci 51 (suppl 1):38-41, 1994
Lotfi AM, Spencer RJ, Ilstrup DM, Melton LJ 3d: Colorectal polyps and the risk of subsequent carcinoma. Mayo Clin Proc 61(5):337-343, 1986
O'Brien MJ, Winawer SJ, Zauber AG, Gottlieb LS, Sternberg SS, Diaz B, Dickersin GR, Ewing S, Geller S, Kasimian D: The National Polyp Study: patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas. Gastroenterology 98(2):371-379, 1990
Shinya H, Wolff WI: Morphology, anatomic distribution and cancer potential of colonic polyps. Ann Surg 190(6):679-683, 1979
Hixson LJ, Fennerty MB, Sampliner RE, McGee D, Garewal H: Prospective study of the frequency and size distribution of polyps missed by colonoscopy. J Nat1 Cancer Inst 82(22):1769-1772, 1990
Neugut AI, Jacobson JS, Ahsan H, Santos J, Garbowski GC, Forde KA, Treat MR, Waye J: Incidence and recurrence rates of colorectal adenomas: a prospective study. Gastroenterology 108(2):402-408, 1995
Griffioen G, Cornelisse CJ, Verspaget HW, Sier CF, Eulderink F, Bosman FT, Lamers CB: Association of aneuploidy in index adenomas with metachronous colorectal adenoma development and a comparison. Cancer 70(8):2035-2043, 1992
Saleh HA, Aburashed A, Bober P, Tabaczka P: P53 protein immunohistochemical expression in colonic adenomas with and without associated carcinoma. Am J Gastroenterol 93(6):980-984, 1998
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sheikh, R.A., Min, B.H., Yasmeen, S. et al. Correlation of Ki-67, p53, and Adnab-9 Immunohistochemical Staining and Ploidy with Clinical and Histopathologic Features of Severely Dysplastic Colorectal Adenomas. Dig Dis Sci 48, 223–229 (2003). https://doi.org/10.1023/A:1021727608133
Issue Date:
DOI: https://doi.org/10.1023/A:1021727608133