Prognostic Value of Proliferative Activity of Ovarian Carcinoma as Revealed by PCNA and AgNOR Analyses

Abstract

Proliferative activity of a malignant tumor is known to reflect its biologic aggressiveness. Proliferating cell nuclear antigen (PCNA) is a marker of cellular proliferation, and silver-stained nucleolar organizer regions (AgNORs) have been shown to correlate with ploidy and proliferative activity of cells depending on the method of assessment; the mean number of AgNORs per nucleus reflects ploidy, whereas the mean percentage of nuclei with five or more AgNORs per nucleus indicates proliferative activity. In ovarian carcinoma, the prognostic value of these markers has not been well defined. We studied PCNA expression and the AgNOR count in 43 ovarian carcinomas (25 serous, 13 mucinous, and 5 clear cell types) to assess their potential prognostic significance compared with the stage of disease and histopathologic features of the tumors. Eight benign (four serous and four mucinous) and six normal ovarian tissues were also evaluated. A standard colloidal silver staining and an immunohistochemical method were used. The mean percentage of PCNA positivity (PCNA index), the mean n u m b e r of AgNORs per nucleus (mAgNOR), and the mean percentage of nuclei with Ovarian carcinoma continues to be the most lethal gynecologic malignancy, ranking as the fifth leading cause of death among women in the United States. Address reprint requests to Dr Ghazizadeh: Central Institute for Electron Microscopic Researches, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113, Japan. more than five AgNORs per nucleus (pAgNOR) for each lesion were determined. In univariable analysis, PCNA indexes and mAgNOR and pAgNOR values were significantly higher in benign ovarian tumors compared with normal ovarian tissues and in adenocarcinomas compared with benign ovarian tumors. In multivariable analysis, PCNA indexes were significantly associated with histologic grade (P=.003), whereas associations of mAgNOR and pAgNOR values were highly significant with both histologic grade and disease stage (P=.0001). Histologic grade, but not subtype, was also associated with disease stage at a significant level (P=.008). Our findings indicate that differences in biologic behavior of ovarian carcinomas may, in part, be defined by differences in their ploidy and proliferative activity, and that whereas PCNA expression is of limited value, assessment of AgNORs holds promise in providing valuable prognostic information on the biologic behavior of the tumors. (Key words: Proliferating cell nuclear antigen; Silver-stained nucleolar organ i z e r r e g i o n s ; O v a r i a n carcinoma; Stage; G r a d e ; S u b t y p e ; Prognosis) Am J Clin Pathol 1997;107:451-458. tumors within the ovary experienced up to 90% cure after surgical treatment; however, about 70% of patients are usually in a more advanced stage at the time of p r e s e n t a t i o n , resulting in a m a r k e d l y decreased overall 5-year survival rate of 38%. Among factors influencing the survival of patients with ovarian carcinoma, early detection and prediction of the prognosis of the dise...

Role of cdk4, p16^INK4, and Rb Expression in the Prognosis of Bronchioloalveolar Carcinomas

“…Many studies have shown that the growth rate differs markedly among tumors [1, 2, 3], and that it closely correlates with prognosis [1, 2, 3, 4]. Hence, it is unclear which factors contribute most to the heterogeneity in the growth potential among tumors.…”

Proliferative activity in oral salivary gland tumors: the role of PCNA and AgNOR assessed by a double staining technique

“…Other studies have also noted a lack of correlation between these indices when analyzed separately in other kinds of tumors (28)(29)(30)(31)(32) .The inadequacy of statistical correlations between the PCNA index and AgNOR counts has been attributed to the fact that these methods quantify different aspects of proliferative activity.…”

Comparison of The Means of Argyrophilic Nucleolar Organizer Region (mAgNOR) Pre- and Post-Therapy in Nasopharyngeal Carcinoma Patients at Wahidin Sudirohusodo General Hospital Makassar

“…But less studies finding a significant relationship between the decrease in the mAgNOR post-therapy with stage. (13,23,24) Chemoradiotherapy is a chemotherapy combined with radiotherapy concurrently used to control tumor lokoregional and improve the survival of patients in order to overcome cancer cells systemically through microcirculation. In this study most of the samples will undergo neoadjuvant chemotherapy intended to reduce the size of the tumor before radiotherapy.…”