p53 expression in tissue adjacent to endometrial carcinoma

Objective: Since several investigations did not demonstrate the presence of altered p53 in endometrial hyperplasias, it has been concluded that these alterations constitute a relatively late event in endometrial carcinoma. The aim of the present study was to assess the presence of p53 in the tissue adjacent to endometrial carcinoma in attempt to elucidate the relationship between these tissues.

Methods: New slides were prepared from paraffin-embeded tissue blocks of 49 endometrial endometrioid carcinoma hysterectomy specimens so that in each case tumor tissue and adjacent uninvolved endometrium were represented. Immunohistochemical staining for p53 detection was then performed.

Results: In 43 of the 49 hysterectomy specimens evaluated, the tissue adjacent to the endometrial carcinoma was non hyperplastic and in six it was hyperplastic. Positive immunohistochemical staining was found in 22 (44.9%) of endometrial carcinomas and in eight (16.3%) of the adjacent tissues. A statistically significant higher percentage of hyperplastic adjacent tissues than non-hyperplastic adjacent tissues were immunohistochemically p53 positive (50.0% vs 11.3%; p = 0.047).

Conclusions: Our findings may indicate that p53 alterations are not necessarily a late event in endometrial endometrioid carcinogenesis. Since a large proportion of tissues adjacent to endometrial carcinoma do not show p53 alterations, other early cellular events may also play a role.

p53; Endometrial carcinoma; Adjacent tissue

[1] Ambros R. A., Vigna P. A., Figge J., Kallakury B. V. S., Mastrangelo A., Eastman A. Y. et al.: "Observations on tumor and metastatic suppressor gene status in endometrial carcinoma with particular emphasis on p53". Cancer, 1994, 73, 1686.

[2] Inoue M., Okayama A., Fujita M., Enomoto T., Sakata M., Tarnzawa O., Ueshima H.: "Clinicopathological characteristics of p53 overexpression in endometrial cancer". int. J. Cancer, 1994, 58, 14.

[3] Ambros R. A., Sheehan C. E., Kallakury B. V. S., Ross J. S., Malfetano J., Paunovich E., Figge J.: "MDM2 and p53 protein expression in the subtypes of endometrial carcinoma". Mod. Pathol., 1996, 9, 1165.

[4] Bur M. E., Periman C., Edelman L., Fey E., Rose P. G.: "P53 expression in neoplasms of the uterine corpus". Am. J. Clin. Pathol., 1992, 98, 81.

[5] Kohler M. F., Berchuk A., Davidoff A. M., Humphrey P.A., Dodge R. K., Iglehart J. D. M. et al.: "Overexpression and mutation of p53 in endometrial carcinoma". Cancer Res., 1992, 52, 1622.

[6] Kaku T., Kamura T., Hirakawa T., Sakai K., Amada S., Kobayashi H., Nakano H.: "Endometrial carcinoma associated with hyperplasia-immunohistochemical study of angiogenesis and p53 expression". Gynecol. Oncol., 1999, 72, 51.

[7] Kohler M. F., Nishii H., Humphrey P. A., Saski H., Marks J., Bast R. C. et al.:''Mutations of the p53 tumor-suppressor gene is not a feature of endometrial hyperplasias". Am. J. Obstet. Gynecol., 1993, 169, 690.

[8] Kohler M. F., Berchuck A., Davidoff A. M. et al.: "Overexpression and mutation of p53 in endometrial carcinoma". Cancer Res., 1992, 52, 1622.

[9] Eissa S., Abu Saada M., el-Sharkawy T.: "Flow cytometric cell cycle kinetics and quantitative measurement of c-erbB-2 and mutant p53 proteins in normal, hyperplastic and malignant endometrial biopsies". Clin. Biochem., 1997, 30, 209.

[10] Vogelstein B., Fearon E. R., Hamilton S. R. et al.: "Genetic alterations during colorectal-tumor development". N. Engl. J. Med., 1988, 319, 525.

[11] Davidoff A. M.. Herndon J. E., Kerns B. J. et al.: "Relation between p53 overexpression and established prognostic factors in breast cancer". Surgery, 1991, 110, 259.

[12] Sozzi G., Miozzo M., Donghi R. et al.: "Deletions of 17p and p53 mutations in preneoplastic lesions of the lung". Cancer Res., 1992, 52, 6079.

[13] Bennet W. P., Hollstein M. C., Metcalf R. A. et al.: "p53 mutations and protein accumulation during multistage human esophageal carcinogenesis". Cancer Res., 1992, 6092.

[14] Ioffe 0. B., Papadimitriou J. C., Drachenberg C. B.: "Correlation of proliferation indices, apoptosis and related oncogene expression (bcl-2, and c-erbB-2) and p53 in proliferative. hyperplastic, and malignant endometrium". Hum. Pathol., 1998, 29, 1150.

[15] Yu C. C., Wilkinson N.. Brito M. J., Buckley C.H., Fox H., Levrnson D. A.: "Patterns of immunohistochemical staining for proliferating cell nuclear antigen and p53 in benign and neoplastic human endometrium". Histopathology, 1993, 23, 367.

[16] Riethdorf L., Begemann C.. Riethdorf S., Milde-Langosch K., Loning T.: "Comparison of benign and malignant endometrial lesions for their p53 state, using immunohistochemestry and temperature- gradient gel electrophoresis". Virchows. Arch., 1996, 428, 47.

[17] Enomoto T., Fujita M., Inoue M., Rice J. M., Nakajima R.. Tanizawa O., Nomura T.: "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., 1993, 15, 1883.

[18] Schneider J., Rubio M. P.. Rodriguez-Escudero F. J., Seizinger B R., Castressane J. S.: "Identification of p53 mutations by means of single strand conformation polymorphism analysis in gynecological tumors: comparison with results of immunohistochemistry". Eur. J. Cancer, 1994, 30A, 504.

[19] MacGeoch C., Barnes D. M., Newton J. A., Mohamed S., Hodgson S. V.. Bishop D. T., Spurr N. K.: "P53 protein detected by immunohistochemical staining is not always mutant". Dis Markers, 1993, 11, 239.

[20] Wynford-Thomas D.: "p53 in tumor pathology: can we trust immunohistochemistry?". J. Pathol., 1992, 166, 329.

[21] Sherman M. E., Bur M. E., Kurman R. J.: "p53 in endometrial cancer and its putative precursors: evidence for diverse pathways of tumorigenesis". Hum. Pathol., 1995, 26, 1268.