Abstract
To further investigate whether multiple genetic changes are involved in the development of colorectal cancer, we performed an immunohistochemical analysis of p53 and ras p21 protein expression in 139 specimens of colorectal adenoma with varying degrees of dysplasia, 57 specimens of early cancer with an adenomatous component, and 12 specimens of superficial early cancer without any adenomatous component. Positive p53 staining was found in 15% of the adenomas with moderate dysplasia and in 42% of the adenomas with severe dysplasia or intramucosal carcinoma (IMCA). Positive immunostaining of p53 was observed to be significantly correlated with the degree of dysplasia and the depth of invasion, as was the expression of ras p21. However, a closer correlation was observed with the increasing size of the adenomas. Furthermore, p53 staining was positive in 42% of the 12 superficial early cancer specimens, while ras staining was positive in only 1 specimen (8%). These results indicate that p53 gene overexpression may play some biological role in both the adenoma-to-carcinoma sequence and in de novo cancer development, whereas ras p21 expression may not be as involved in de novo cancer development as in the malignant conversion of colorectal adenomas.
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References
Muto T, Bussey HJR, Morson BC (1975) The evolution of cancer of the colon and rectum. Cancer 36:2251–2270
Kuramoto S, Oohara T (1988) Minute cancers arising de novo in the human large intestine. Cancer 61:829–834
Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AMM, Bos JL (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319:525–532
Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767
Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, Hedge P, Markham A, Krush AG, Petersen G, Hamilton SR, Nilbert MC, Levy DB, Bryan TM, Preisinger AC, Smith KJ, Su LK, Kinzler KW, Vogelstein B (1991) Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253:665–669
Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, van Tuinen P, Ledbetter DH, Barker DF, Nakamura Y, White R, Vogelstein B (1989) Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244:217–221
Fearon ER, Cho KR, Nigro JM, Kern SE, Simons JW, Ruppert JM, Hamilton SR, Preisinger AC, Thomas G, Kinzler KW, Vogelstein B (1990) Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247:49–56
Fujimori T, Nagasako K, Satonaka K, Hirayama D, Harada M, Muratani A, Tabata T, Kitazawa S, Ikehara H, Maeda M (1992) Expression of ras oncogene product (p21) and point mutation of Ki-ras codon 12 in superficial early colorectal cancer. (in Japanese with English abstract) I to Chou (Stomach Intestine) 27:111–117
Yamagata S, Muto T, Uchida Y, Masaki T, Sawada T, Tsuno N, Hirooka T (1994) Lower incidence of K-ras codon 12 mutation in flat colorectal adenomas than in polypoid adenomas. Jpn J Cancer Res 85:147–151
Japanese Research Society for Cancer of the Colon and Rectum (1994) General rules for clinical and pathological studies on cancer of the colon, rectum, and anus (in Japanese). Kanehara, Tokyo, pp 49–73
Levin AJ, Momand J, Finlay CA (1991) The p53 tumor suppressor gene. Nature 351:453–456
Baker SJ, Preisinger AC, Jessup JM, Paraskeva C, Markowitz S, Willson JKV, Hamilton S, Vogelstein B (1990) p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res 50:7717–7722
Oren M (1985) The p53 cellular tumor antigen: gene structure, expression and protein properties. Biochem Biophys Acta 823:67–68
Vahakangas KH, Samet JM, Metcalf RA, Welsh JA, Bennett WP, Lane DP, Harris CC (1992) Mutations of p53 and ras genes in radon-associated lung cancer from uranium miners. Lancet 339:576–580
Cunningham J, Lust JA, Schaid DJ, Bren GD, Carpenter HA, Rizza E, Kovach JS, Thibodeau SN (1992) Expression of p53 and 17p allelic loss in colorectal carcinoma. Cancer Res 52:1974–1980
Kihara T, Tsuda H, Teshima S, Okada S, Matsuura S, Hirohashi S (1992) High incidence of p53 gene mutation in human ovarian cancer and its association with nuclear accumulation of p53 protein and tumor DNA aneuploidy. Jpn J Cancer Res 83:978–984
Wagata T, Shibagaki I, Imamura M, Shimada Y, Toguchida J, Yandell DW, Ikenaga M, Tobe T, Ishizaki K (1993) Loss of 17p, mutation of the p53 gene, and overexpression of p53 protein in esophageal squamous cell carcinomas. Cancer Res 53:846–850
Rodrigues NR, Rowan A, Smith MEF, Kerr IB, Bodmer WF, Gannon JV, Lane DP (1990) p53 mutations in colorectal cancer. Proc Natl Acad Sci 87:7555–7559
Yamaguchi A, Kurosaka Y, Fushida S, Kanno M, Yonemura Y, Miwa K, Miyazaki I (1992) Expression of p53 protein in colorectal cancer and its relationship to short-term prognosis. Cancer 70:2778–2784
Koide A (1993) Overexpression of p53 in colorectal tumors: An immunohistochemical study (in Japanese with English abstract). Nippon Daichokomonbyo Gakkaizasshi (J Jpn Soc Coloproctol) 46:20–26
Purdie CA, Grady JO, Piris J, Wyllie AH, Bird CC (1991) p53 expression in colorectal tumors. Am J Pathol 138:807–813
Pignatelli M, Stamp GWH, Kafiri G, Lane D, Bodmer WF (1992) Over-expression of p53 nuclear oncoprotein in colorectal adenomas. Int J Cancer 50:683–688
Miyaki M, Seki M, Okamoto M, Yamanaka A, Maeda Y, Tanaka K, Kikuchi R, Iwama T, Ikeuchi T, Tonomura A, Nakamura Y, White R, Miki Y, Utsunomiya J, Koike M (1990) Genetic changes and histopathological types in colorectal tumors from patients with familial adenomatous polyposis. Cancer Res 50:7166–7173
Jansson DS, Radosevich JA, Carney WP, Rosen ST, Schlom J, Staren ED, Hyser MJ, Gould VE (1990) An immunohistochemical analysis of ras oncogene expression in epithelial neoplasms of the colon. Cancer 65:1329–1337
Grinnell RS, Lane N (1958) Benign and malignant adenomatous polyps and papillary adenomas of the colon and rectum. An analysis of 1856 tumors in 1335 patients. Int Abst Surg 106:519–538
Muto T (1993) Polyp and polyposis of large bowel (in Japanese). Igaku Shoin, Tokyo, pp 28–105
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Ieda, S., Watatani, M., Yoshida, T. et al. Immunohistochemical analysis of p53 and ras p21 expression in colorectal adenomas and early carcinomas. Surg Today 26, 230–235 (1996). https://doi.org/10.1007/BF00311580
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DOI: https://doi.org/10.1007/BF00311580