Determination of cell proliferative activity by immnunohistochemical detection of proliferating cell nuclear antigen in N‐methyl nitrosoureainduced rat mammary tumours

Abstract

Rodent experimental models are considered useful experimental systems to study mammary cancer, which occurs in rodents as a result of hormonal imbalance, much like the breast cancer in women. Rodent cells are easier to transform by chemical carcinogen due to their relatively poorer controls of genetic stability and DNA repair systems. Proliferating cell nuclear antigen (PCNA) is one of the most sensitive biomarkers to measure the cell proliferative activities in the neoplasms, especially when the otherwise undetectable PCNA protein overâ€expresses to the immunohistochemically detectable levels. In the present study, mammary tumours were induced in Sprague Dawley rats by intraperitoneal administration of Nâ€methyl nitrosourea (MNU) chemical carcinogen. Palpable tumours were noticed after 60 days postinjection (dpi) with average latency period of 144 days, and 12 (46.15%) of 26 rats developed mammary tumours. A total of 18 tumours were diagnosed in 12 rats, including 2 cases (10%) of hyperplasia, 1 (5%) benign and 17 malignant tumours (85%). Malignant tumours included in situ ductal papillary carcinoma (11.11%), in situ ductal cribriform carcinoma (38.88%), invasive tubular adenocarcinoma (5.56%), invasive papillary carcinoma (16.67%) and invasive cribriform carcinoma (22.22%) were. PCNA immunohistochemistry revealed moderate to strong nuclear staining in neoplastic cells, with highest mean PCNA index of 55.53±10.13 in invasive cribriform carcinoma. The PCNA indices were significantly different (p<0.01; one way ANOVA) between control mammary gland, hyperplasia, benign and malignant tumours. It was concluded that the measurement of PCNA expressing cells employing immunohistochemistry can help in the determination of the level of malignancy in MNUâ€induced rat mammary tumours.