Abstract
To clarify whether p53 protein expression is involved in multistep carcinogenesis or the progression of mammary ductal carcinoma, we investigated p53 protein expression in 83 invasive ductal carcinomas (IDC), 10 IDC with a predominant intraductal component, 13 non-invasive ductal carcinoma (NIDC), 16 atypical ductal hyperplasia (ADH) and 39 benign epithelial hyperplasia (EH), using immunohistochemistry. Expression of p53 protein was detected in 24 (28.9%) cases of IDC, 5 (50%) cases of IDC with a predominant intraductal component and 1 (7.6%) case of NIDC. No expression was observed in either ADH or EH. In IDC, including cases with a predominant intraductal component, p53 protein expression was associated with a higher histological grade (P<0.0001) or mitotic index (P<0.0005). Although overexpression of c-erbB-2 protein has also shown a similar association with these prognostic indicators, expression of p53 protein correlated regardless of the status of c-erbB-2 overexpression. Completely coordinated expression of p53 protein was seen in both intraductal and invasive components. The intraductal component in IDC including cases with a predominant intraductal component which expresses p53 protein had significantly higher histological grade (P<0.0005) or more comedo-subtypes (P<0.0001). These results suggested that p53 protein expression occurs at a stage of NIDC with high histological grade or in comedo-subtypes. Its expression is maintained throughout invasion.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baak JPA, Dop HV, Kurver PHJ, Hermans J (1985) The value of morphometry to classic prognosticators in breast cancer. 56: 374–382
Barnes DM, Dublin EA, Fisher CJ, Levison DA, Millis RR (1993) Immunohistochemical detection of p53 protein in mammary carcinoma: an important new independent indicator of prognosis? Hum Pathol 24: 469–476
Bartek J, Bartkova J, Vojtesek B, Staskova Z, Rejthar A, Kovarik J, Lane DP (1990) Pattern of expression of the p53 tumor suppressor gene in human breast tissues and tumors in situ and in vitro. Int J Cancer 46: 839–844
Bloom HGJ, Richardson WW (1957) Histologic grading and prognosis in breast cancer. Br J Cancer 11: 655–669
Davidoff AM, Kerns BJM, Iglehart JD, Marks JR (1991) Maintenance of p53 alterations throughout breast cancer progression. Cancer Res 51: 2605–2610
Esrig D, Spruck CH III, Nichols PW, Chaiwun B, Steven K, Groshen S, Skinner SCCDG, Jones PA, Cote RJ (1993) p53 nuclear protein accumulation correlates with mutations in the p53 gene, tumor grade, and stage in bladder cancer. Am J Pathol 143: 1389–1397
Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 235: 49–53
Isola J, Visakorpi T, Holli K, Kallioniemi OP (1992) Association of overexpression of tumor suppressor protein p53 with rapid cell proliferation and poor prognosis in node-negative breast cancer patients. J Natl Cancer Inst 84: 1109–1114
Iwaya K, Tsuda H, Hiraide H, Tamaki K, Tamakuma S, Fukutomi T, Mukai K, Hirohashi S (1991) Nuclear p53 immunoreaction associated with poor prognosis of breast cancer. Jpn J Cancer Res 82: 835–840
Levine AJ, Momand J, Finlay CA (1991) The p53 tumor suppressor gene. Nature 351: 453–456
Midgley CA, Fisher CJ, Bartek J, Vojtesek B, Lane D, Barnes DM (1992) Analysis of p53 expression in human tumours: an antibody raised against human p53 expressed in Escherichia coli. J Cell Sci 101: 183–189
Mori S, Akiyama T, Morishita Y, Shimizu S, Sakai K, Sudoh K, Toyoshima K, Yamamoto T (1987) Light and electron microscopical demonstration of c-erbB-2 gene product-like immunoreactivity in human malignant tumours. Virchows Arch [B] 54: 8–15
Odermatt BF, Lang AB, Ruttner JR, Winterhalter KH, Trueb B (1984) Monoclonal antibodies to human type IV collagen: useful reagents to demonstrate the heterotrimeric nature of the molecule. Proc Natl Acad Sci USA 81: 7343–7347
Page DL (1992) The clinical significance of mammary epithelial hyperplasia. Breast 1: 3–7
Page DL, Anderson TJ (1987) Epithelial hyperplasia. In: Page DL, Anderson TJ (eds) Diagnostic histopathology of the breast. Churchill Livingstone, New York, pp 120–156
Poller DN, Roberts EC, Bell JA, Elston CW, Blawey RW, Ellis AIO (1993) p53 protein expression in human ductal carcinoma in situ: relationship to immunohistochemical expression of estrogen receptor and c-erbB-2 protein. Hum Pathol 24: 463–468
Reihsaus E, Kohler M, Kraiss S, Oren M, Montenarh M (1990) Relationship of the level of the oncoprotein p53 in non-transformed and transformed cells. Oncogene 5: 137–145
Tsuda H, Hirohashi S, Shimosato Y, Hirota T, Tsugane S, Watanabe S, Terada M, Yamamoto H (1990) Correlation between histologic grade of malignancy and copy number of c-erbB-2 gene in breast carcinoma. Cancer 65: 1794–1800
Tsuda H, Iwaya K, Fukutomi T, Hirohashi S (1993) p53 mutation and c-erbB-2 amplification in intraductal and invasive breast carcinomas of high histologic grade. Jpn J Cancer Res 84: 394–401
Walker RA, Dearing SJ, Lane DP, Varley JM (1991) Expression of p53 protein in infiltrating and in-situ breast carcinomas. J Pathol 165: 203–211
World Health Organization (1981) Histological typing of breast tumors, 2nd edn. pp 18–19
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Umekita, Y., Takasaki, T. & Yoshida, H. Expression of p53 protein in benign epithelial hyperplasia, atypical ductal hyperplasia, non-invasive and invasive mammary carcinoma: an immunohistochemical study. Vichows Archiv A Pathol Anat 424, 491–494 (1994). https://doi.org/10.1007/BF00191434
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00191434