Abstract
Mutations of the tumour suppressor p53 gene have been reported in a variety of human malignant tumours, and are frequently associated with over-expression of p53 protein. To examine the significance of p53 gene alteration in endometrial carcinomas, we studied the immunohistochemical reactivity with a monoclonal antibody against p53 (PAb 1801) in 30 endometrial carcinomas as well as in 64 normal endometria. The presence or absence of correlation of p53 over-expression with the clinicopathological features and with the immunohistochemical expression of sex steroid receptors (oestrogen receptors; ER, progesterone receptors; PR) was also analysed. Expression of p53 was found in none of 64 normal endometria, but was identified in 5 of the 30 (16.7%) endometrial carcinomas. All 5 of the p53-positive tumours developed in women more than 3 years post-menopause, whereas the carcinomas in 5 pre-menopausal women and 3 women less than 3 years post-menopause were p53-negative. None of the 5 p53-positive carcinomas was associated with adjacent endometrial hyperplasia. Two of the 5 p53-positive tumours showed non-endometrioid histology: serous papillary and clear cell carcinomas. In contrast, 6 carcinomas accompanied by adjacent hyperplasia were p53-negative. In addition, ER and/or PR expression was found in none of the 5 p53-positive tumours, but was present in 21 of the 25 p53-negative tumours (p<0.01). These clinicopathological features of p53-positive carcinomas and the inverse correlation of p53 immunoreactivity with sex steroid receptor status suggest that p53 over-expression is frequent in a specific category of endometrial carcinoma, presumably oestrogen-unrelated tumours.
Similar content being viewed by others
References
Banks L, Matlashewski G, Crawford L (1986) Isolation of human-p53-specific monoclonal antibodies and their use in the studies of human p53 expression. Eur J Biochem 159:529–534
Bergeron C, Ferenczy A, Shyamala G (1988) Distribution of estrogen receptors in various cell types of normal, hyperplastic, and neoplastic human endometrial tissues. Lab Invest 58:338–345
Bokhman JV (1983) Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 15:10–17
Brustein S, Fruchter R, Greene GL, Pertshuck LP (1989) Immunohistochemical assay of progesterone receptors in paraffin-embedded specimens of endometrial carcinoma and hyperplasia: a preliminary evaluation. Mod Pathol 2:449–455
Caamano J, Ruggeri B, Momiki S, Sicker A, Zhang SY, Klein-Szanto AJP (1991) Detection of p53 in primary lung tumors and non-small cell lung carcinoma cell lines. Am J Pathol 139:839–845
Carcangiu ML, Chambers JT, Voynick IM, Pirro M, Schwartz PE (1990) Immunohistochemical evaluation of estrogen and progesterone receptor content in 183 patients with endometrial carcinoma. Am J Clin Pathol 94:247–254
Cattoretti G, Rilke F, Andreola S, D'Amato L, Delia D (1988) p53 expression in breast cancer. Int J Cancer 41:178–183
Chen PL, Chen YM, Bookstein R, Lee WH (1990) Genetic mechanisms of tumor suppression by the human p53 gene. Science 250:1576–1580
Davidoff AM, Humphrey PA, Iglehart JD, Marks JR (1991) Genetic basis for p53 overexpression in human breast cancer. Proc Natl Acad Sci USA 88:5006–5010
Deligdish L, Cohen C (1985) Histologic correlates and virulence implications of endometrial carcinoma associated with adenomatous hyperplasia. Cancer 56:1452–1455
Deligdish L, Holinka CF (1986) Progesterone receptors in two groups of endometrial carcinoma. Cancer 57:1385–1388
Eccles DM, Brett L, Lessells A, Gruber L, Lane D, Steel CM, Leonard RCF (1992) Overexpression of the p53 protein and allele loss at 17p13 in ovarian carcinoma. Br J Cancer 65:40–44
Enomoto T, Fujita M, Inoue M, Rice JM, Nakajima R, Tanizawa O, Nomura T (1993) Alterations of the p53 tumor suppressor gene and its association with activation of the c-K-ras-2 protooncogene in premalignant and malignant lesions of the human uterine endometrium. Cancer Res 53:1883–1888
Finlay CA, Hinds PW, Tan TH, Eliyahu D, Oren M, Levine AJ (1988) Activating mutations for transformation by p53 produce a gene product that forms an hsp70-p53 complex with an altered half-life. Mol Cell Biol 8:531–539
Finlay CA, Hinds PW, Levine AJ (1989) The p53 proto-oncogene can act as a suppressor of transformation. Cell 57:1083–1093
Gambrell RD, Bagnell CA, Greenblatt RB (1983) Role of estrogens and progesterone in the etiology and prevention of endometrial cancer: review. Am J Obstet Gynecol 146:696–707
Gurpide E (1991) Endometrial cancer: biochemical and clinical correlates. J Natl Cancer Inst 83:405–416
Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253:49–53
Honda T, Kato H, Imamura T, Gima T, Nishida J, Sasaki M, Hoshi K, Sato A, Wake N (1993) Involvement of p53 gene mutation in human endometrial carcinomas. Int J Cancer 53:963–967
Iggo R, Gatter K, Bartek J, Lane D, Harris AL (1990) Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet 335:675–679
Janne O, Kauppila A, Kontula K, Syrjala P, Vihko R (1979) Female sex steroid receptors in normal, hyperplastic and carcinomatous endometrium. The relationship to serum steroid hormones and gonadotropins and changes during medroxyprogesterone acetate administration. Int J Cancer 24:545–554
Kohler MF, Berchuck A, Davidoff AM, Humphrey PA, Dodge RK, Iglehart JD, Soper JT, Clarke-Pearson DL, Bast RC, Marks JR (1992) Overexpression and mutation of p53 in endometrial carcinoma. Cancer Res 52:1622–1627
Kurman RJ, Norris HJ (1987) Endometrial carcinoma. In: Kurman RJ (ed) Blaustein's pathology of the female genital tract (3rd edn). Springer, Berlin Heidelberg New York, p 338
Kurman RJ, Kaminski PF, Norris HJ (1985) The behavior of endometrial hyperplasia. Cancer 56:403–412
Levine AJ, Momand J, Finlay CA (1991) The p53 tumour suppressor gene. Nature 351:453–456
Marks JR, Davidoff AM, Kerns BJ, Humphrey PA, Pence JC, Dodge RK, Clarke-Pearson DL, Bast RC, Berchuck A (1991) Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res 51:2979–2984
Naito M, Satake M, Sakai E, Hirano Y, Tsuchida N, Kanzaki H, Ito Y, Mori T (1992) Detection of p53 gene mutations in human ovarian and endometrial cancers by polymerase chain reaction-single strand conformation polymorphism analysis. Jpn J Cancer Res 83:1030–1036
Noyes RW, Hertig AT, Rock J (1950) Dating the endometrial biopsy. Fertil Steril 1:3–10
Okamoto A, Sameshima Y, Yokoyama S, Terashima Y, Sugimura T, Terada M (1990) Frequent alleic losses and mutations of the p53 gene in human ovarian cancer. Cancer Res 51:5171–5176
Okamoto A, Sameshima Y, Yamada Y, Teshima S, Terashima Y, Terada M, Yokota J (1991) Alleic loss on chromosome 17p and p53 mutations in human endometrial carcinoma of the uterus. Cancer Res 51:5632–5636
Purdie CA, O'Grady J, Piris J, Wyllie AH, Bird CC (1991) p53 expression in colorectal tumors. Am J Pathol 138:807–813
Reich NC, Levine AJ (1984) Growth regulation of a cellular tumour antigen, p53, in nontransformed cells. Nature 308:199–201
Rodrigues NR, Rowan A, Smith MEF, Kerr IB, Bodmer WF, Gannon JV, Lane DP (1990) p53 mutations in colorectal cancer. Proc Natl Acad Aci USA 87:7555–7559
Sasaki H, Nishii H, Takahashi H, Tada A, Furusato M, Terashima Y, Siegal GP, Parker SL, Kohler MF, Berchuck A, Boyd J (1993) Mutation of the Kiras protooncogene in human endometrial hyperplasia and carcinoma. Cancer Res 53:1906–1910
Scott N, Sagar P, Stewart J, Blair GE, Dixon MF, Quirke P (1991) p53 in colorectal cancer: clinicopathological correlation and prognostic significance. Br J Cancer 63:317–319
Wang DP, Konishi I, Koshiyama M, Mandai M, Nanbu Y, Ishikawa Y, Mori T, Fujii S (1993) Expression of c-erbB-2 protein and epidermal growth factor receptor in endometrial carcinomas: correlation with clinicopathology and sex steroid receptor status. Cancer (in press)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Koshiyama, M., Konishi, I., Wang, Dp. et al. Immunohistochemical analysis of p53 protein over-expression in endometrial carcinomas: Inverse correlation with sex steroid receptor status. Vichows Archiv A Pathol Anat 423, 265–271 (1993). https://doi.org/10.1007/BF01606889
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01606889