This paper is only available as a PDF. To read, Please Download here.
Objective. Paget's disease of the vulva (PDV) and Paget's disease of the breast (PDB) are uncommon diseases, accounting for approximately 1% of all vulval neoplasms and 0.5–4% of all breast cancers, respectively. In 10–30% of vulval cases an invasive adenocarcinoma is present. In such cases the disease is often aggressive and recurrence rate is high. This is in contrast to PDB where the general consensus is that almost all cases are associated with an in situ or invasive ductal carcinoma. Our aim was to examine the presence of the tumor suppressor protein p53 and the proliferation marker Ki67 in PDV and PDB and correlate any differences in the expression of these two proteins with the presence of an underlying carcinoma.
Methods. Immunohistochemistry was performed on 52 archival cases of PDV, which included 10 with associated invasive adenocarcinoma of the vulva, and on 37 archival cases of PDB, including 26 with available associated ductal carcinoma in situ (DCIS) or invasive carcinoma of the breast. All cases were formalin-fixed and paraffin wax-embedded. Monoclonal antibodies were used with microwave antigen retrieval. Streptavidin–biotin-horseradish peroxidase and 3,3′-diaminobenzidine detection methods were employed to visualize antibody binding and staining. A section was scored positive for p53 if more than 10% of cell nuclei were stained brown and Ki67 was expressed as a percentage of positive cells to the nearest 5% of cells showing nuclear positivity (Ki67 staining index).
Results. p53 was expressed in 15 of 52 (29%) PDV cases and 5 of 37 (13%) cases of PDB. Four of the ten cases (40%) of PDV associated with invasive disease expressed p53 compared with 11 of 42 (26%) cases without invasive disease. The mean Ki67 staining index for PDV associated with invasion was 19%, and for that without invasion, 16%. In the breast cases, the mean staining index was 11%.
Conclusion. Our data suggest that p53 may have a role to play in PDV progression, and may be a late event in some cases, especially those associated with invasive disease. Ki67 has no apparent prognostic role in PDV as there was no significant difference between those cases associated with and those without invasive disease. Neither p53 nor Ki67 appears to have a prognostic role to play in PDB.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Gynecologic Oncology
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Paget's disease of the vulva.Br J Dermatol. 1901; 13: 407-413
- Extrammary Paget's disease: prognosis and relationship to internal malignancy.J Am Acad Dermatol. 1985; 113: 1009-1013
- Paget's disease and apocrine gland carcinoma of the vulva.Obstet Gynaecol. 1971; 38: 185-192
- Paget's disease of the vulva: prevalence of associated vulvar adenocarcinoma, invasive Paget's disease, and recurrence after surgical excision.Am J Obstet Gynecol. 1998; 180: 24-28
- Mammary Paget's disease and an associated carcinoma: an immunohistochemical study.Arch Pathol Lab Med. 1993; 117: 291-294
- p53 mutations in human cancers.Science. 1991; 253: 49-53
- Suppression of human colorectal cell growth by wild type p53.Science. 1990; 249: 912-915
- Detection of p53 point mutations in primary human vulvar cancer by PCR and temperature gradient gel electrophoresis.Gynecol Oncol. 1997; 64: 93-98
- Mutation of tumour suppressor gene p53 is frequently found in vulvar carcinoma cells.Am J Obstet Gynaecol. 1995; 173: 1477-1482
- Prognostic factors in Paget's disease of the vulva: a study of 21 cases.Int J Gynecol Pathol. 1999; 18: 351-359
- Ki67 and other proliferating markers useful for immunohistological diagnostic and prognostic evaluations in human malignancies.Semin. Cancer Biol. 1990; 1: 99-206
- p53 protein expression in mammary and extramammary Paget's disease.Anticancer Res. 1993; 13: 2429-2434
- Tumour cells of extramammary Paget's disease do not show either p53 mutation or alleic loss at several selected loci implicated in other cancers.Br J Cancer. 1997; 76: 904-908
- DNA ploidy and expression of p53 and C-erbB-2 in extramammary Paget's disease of the vulva.Gynecol Oncol. 1997; 64: 88-92
- p53 expression in benign and malignant skin tumours.Br J Dermatol. 1993; 128: 237-241
- Prognostic value of Ki67 antigen expression in basal cell carcinomas.Br J Dermatol. 1995; 133: 737-741
- Expansion of the Ki67 proliferative compartment correlates with degree of dysplasia in Barrett's esophagus.Cancer. 1995; 75: 423-429
- Ki67 expression in vulvar carcinoma.Int J Gynecol Pathol. 1994; 13: 205-210
- Immunohistochemical study of mammary and extramammary Paget's disease.Anticancer Res. 1995; 15: 467-470
- p53 immunohistochemical analysis in breast cancer with four monoclonal antibodies: comparison of staining and PCR-SSCP results.Br J Cancer. 1994; 69: 846-852
- Accumulation of p53 tumour suppressor protein: an independent marker of prognosis in breast cancers.J Natl Cancer Inst. 1992; 84: 845-855
- p53 in node-negative breast carcinoma: an immunohistochemical study of epidemiologic risk factors, histologic features, and prognosis.J Clin Oncol. 1995; 13: 821-830
- Association of p53 protein expression with tumour cell proliferation rate and clinical outcome in node negative breast cancer.J Natl Cancer Inst. 1993; 85: 201-206
- p53 as an independent prognostic marker in lymph node-negative breast cancer patients.J Natl Cancer Inst. 1993; 85: 965-970
- Evaluation of cell proliferation in breast carcinoma: comparison of Ki67 immunohistochemical study, DNA flow cytometric analysis, and mitotic count.Cancer. 1990; : 1180-1184
- Ki67 immunostaining in primary breast cancer: pathological and clinical associations.Br J Cancer. 1989; 59: 943-947
- Comparison of monoclonal antibody Ki 67 reactivity with grade and DNA flow cytometry of breast carcinomas.Br J Cancer. 1988; 57: 281-283
- The prognostic significance of epidermal growth factor receptor (EGFR), C-erbB-2, Ki67 and PCNA expression in breast cancer.Anticancer Res. 1996; 16: 3141-3148
- p53 protein in benign and malignant sweat gland tumours.Am J Dermatopathol. 1994; 16: 126-129
Received: July 18, 2001
☆Presented at the British Society for the Study of Vulval Disease, Manchester, September 2000, and at the British Association of Surgical Oncologists, London, November 2000.
© 2002 Elsevier Science (USA). Published by Elsevier Inc. All rights reserved.