Mutations of the p53 tumor suppressor gene often occur in a variety of human malignant tumors and are frequently associated with overexpression of p53 protein. This study was designed to examine indirectly the frequency of p53 protein in primary endometrial carcinoma and to correlate the overexpression with steroid hormone receptor status including pS2 protein status. The study was performed on 79 formalinfixed, paraffin-embedded tissues of endometrial carcinoma. P53 protein overexpression was detected by means of immunohistochemistry using monoclonal antibody NCL-p53-D07. Estrogen and progesterone receptor status was determined by immunohistochemistry using the monoclonal antibodies NCL-ER-LH2 and NCL-PGR, respectively, and the pS2 protein using polyclonal antibody NCL-pS2. Overexpression of p53 protein was found in 27 (34%) of the 79 endometrial carcinomas. A strong positive relationship was demonstrated between histologic grade and p53 protein overexpression. There was a significant correlation between p53 protein overexpression and negative estrogen receptor status (49%) negative progesterone receptor status (49%) as well as a negative pS2 protein (45%). The results suggest that overexpression of p53 is associated with high malignant potential. However, p53 overexpression itself does not appear to be an independent prognostic factor in endometrial carcinomas.
1. Vogelstein B, Kinzler KW. P53 function and dysfunction. Cell70:523-526, 1992
2.
2. Reich NC, Levine AJ. Growth regulation of a cellular tumor antigen, p53, in nontransformed cells. Nature (Lond.)308:199-201, 1984
3.
3. Shaulsky G, Ben Zeev A, Rotter V.Subcellular distribution of the p53 protein during the cell cycle of Balb/c 3T3 cells. Oncogene5:1707-1711, 1990
4.
4. Steinmeyer K, Maacke H, Deppert W.Cell cycle control by p53 in normal (3T3) and chemically transformed (Meth A) mouse cells. I. Regulation of p53 expression. Oncogene5:1691-1699, 1990
5.
5. Sturzbecher HW, Maimets T, Chumakov P, Brain R, Addison C, et al. P53 interacts with p34cdc2 in mammalian cells: Implications for cell cycle control and oncogenesis. Oncogene5:795-801, 1990
6.
6. Kohler MF, Berchuck A, et al. Overexpression and mutation of p53 in endometrial carcinoma. Cancer. 52:1622-1627, 1992
7.
7. Lane DP. P53, guardian of the genome. Nature358:15-16, 1992
8.
8. Chen PL, Chen YM, et al. Genetic mechanisms of tumor suppression by the human p53 gene. Science250:1576-1580, 1990
10. Hollstein M, Sidransky D, Vogelstein B, Harris CC. P53 mutations in human cancers. Science253:49-53, 1991
11.
11. Marks JR, Davidoff AM, Kerns BJ, Humphrey PA, et al. Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res51:2979-2984, 1991
12.
12. Banks L, Matlashewski G, Crawford L.Isolation of human-p53-specific monoclonal antibodies and their use in the studies of human p53 expression. Eur J Biochem159:529-534, 1986
13.
13. Hollstein M, Sidransky D, et al. P53 mutations in human cancers. Science253:49-531991
14.
14. Lsevine AJ, Momand J, et al. The p53 tumor suppressor gene. Nature531:453-456, 1991
15.
15. Oren M, Maltzman W, Levine AJ. Posttranslational regulation of the 54kd cellular tumor antigen in normal and transformed cells. Mol Cell Biol1:101-110, 1981
16.
16. Bur ME, Perlman C, Edelmann L, Fey E, Rose PG. P53 expression in neoplasms of the uterine corpus. Am J Clin Pathol98:81-87, 1992
17.
17. Risinger JI, Dent GA, Ingar-Trowbridge D, McLachlen JA, Tsao MS, et al. P53 gene mutations in human endometrial carcinoma. Mol Carcingen5:250-253, 1992
18.
18. Kohler MF, Berchuck A, Davidoff AM, Humphrey PA, Dodge RK, et al. Overexpression and mutation of p53 in endometrial carcinoma. Cancer Res52:1622-1627, 1992
19.
19. Jiko K, Sassano H, Ito K, Ozawa N, Sato S, Yajima A.Immunohistochemical and in situ hybridization analysis of p53 in human endometrial carcinoma of the uterus. Anticancer Res13:305-310, 1993
20.
20. Enomoto T, Fujita M, Inoue M, Rice JM, Nakajima R, et al. 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 Res53:1883-1888, 1993
21.
21. Koshiyama M, Konishi I, Wang DP, Mandai M, Komatsu T, et al. Immunohistochemical analysis of p53 protein overexpression in endometrial carcinomas: Inverse correlation with sex steroid receptor status. Virchows Archiv A Pathol Anat423:265-271, 1993
22.
22. Reinartz JJ, George E, Lindgren BR, Niehans GA. Expression of p53, transforming growth factor alpha, epidermal growth factor receptor, and c-erbB-2 in endometrial carcinoma and correlation with survival and known predictors of survival. Hum Pathol25:1075-1083, 1994
23.
23. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol15:10-17, 1983
24.
24. Connelly PJ, Alberhasky RC, Christopherson WM. Carcinoma of the endometrium: Analysis of 865 cases of adenocarcinoma and adenoacanthoma. Obstet Gynecol59:569-574, 1982
25.
25. Okamoto A, Sameshima Y, Yamada Y, Teshima S, Terashima Y, et al. Allelic loss on chromosome 17p and p53 mutations in human endometrial carcinoma of the uterus. Cancer Res51:5632-5636, 1991
26.
26. Inoue M, Okayama A, Fujita M, Enomoto T, Sakata M, et al. Clinicopathological characteristics of p53 overexpression in endometrial cancers. Int J Cancer58:14-19, 1994
27.
27. Ito K, Watanabe K, Nasim S, Sasano H, Sato S, et al. Prognostic significance of p53 overexpression in endometrial cancer. Cancer Res54:4667-4670, 1994
28.
28. Battifora H.P53 immunohistochemistry—a word of caution. Editorial, Hum Pathol25:435-437, 1994
29.
29. Allred DC, Clark GM, et al. Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst85:200-206, 1993
30.
30. Palmer DC, Muir IM, Alexander Al, Cauchi M, Bennett RC, et al. The prognostic importance of steroid receptors in endometrial carcinoma. Obstet Gynecol72:388-393, 1988
31.
31. Nyholm HC, Nielsen AL, Lyndrup J, Norup P, Thorpe S.Biochemical and immunohistochemical evaluation of estrogen and progesterone receptors in endometrial carcinoma and adenomatous hyperplasia: Correlations with stage, grade, and other clinicopathological features. Am J Obstet Gynecol167:1334-1342, 1992
32.
32. Morris PC, Anderson JR, Anderson B, Buller RE. Steroid hormone receptor content and lymph node status in endometrial cancer. Gynecol Oncol56:406-411, 1995
33.
33. Masiakowski P, Breathnach R, Bloch J, Gannon F, Krust A, Chambon P.Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast cancer cell line. Nucleic Acids Res10:7895-7903, 1982
34.
34. Rio MC, Bellocq JP, Gairard B, Rasmussen UB, Krust A, et al. Specific expression of the pS2 gene in subclasses of breast cancers in comparison with expression of the estrogen and progesterone receptors and the oncogene erbB2. Proc Natl Acad Sci USA84:9243-9247, 1987
35.
35. Schwartz LH, Koerner F, Edgerton SM, Sawicka JM, Rio MC, Bellocq JP, Chambon P, Thor AD. PS2 expression and response to hormonal therapy in patients with advanced breast cancer. Cancer Res51:624-628, 1991
