Assessment of nucleolar organizer regions by automatic image analysis in breast cancer: correlation with DNA content, proliferation rate, receptor status and histopathological grading

Abstract

The value of automatic image analysis in the investigation of nucleolus regions (AgNOR) has been examined in tissue sections of 52 malignant and 30 benign breast lesions. Determination of the AgNOR number per cell alone revealed a considerable overlap between benign (range 1.2-3.8) and malignant specimens (range 1.5-16.2). They differed however, highly significantly (P less than 0.001) in their AgNOR sizes. In benign breast disorders the mean AgNOR area per tumour ranged from 0.22 microns2 to 1.07 microns2 (mean 0.39 microns2), whereas in carcinomas AgNOR sites ranged from 0.05 microns2 to 0.22 microns2 (mean 0.09 microns2). AgNOR counts showed a good correlation with histopathological grade (P less than 0.05), aneuploidy (P less than 0.01), proliferation rate as determined by Ki67 immunostaining (P less than 0.01), as well as oestrogen and progesterone receptor content (P less than 0.01). Image analysis proved to be advantageous over AgNOR counting alone as it facilitated the standardization of the AgNOR technique itself and thus, significantly improved its diagnostic specifity.

Significance of AgNOR Count in Differentiating Malignant Cells from Reactive Mesothelial Cells in Serous Effusions

“…An inverse ratio between AgNOR number and size was observed in their study. Ruschoff 19 also found such a ratio between AgNOR number and area. As shown in Table I and Figure 1, benign mesothelial cells revealed a low AgNOR count (mean, 1.92) but slightly enlarged single dots, whereas malignancies exhibited a greater number but smaller, irregular AgNOR dots (Figure 2).…”

Demonstration of silver-stained nucleolar organizer region associated proteins (AgNORs) after wet autoclave pretreatment in breast carcinoma: Correlation to tumor stage and long-term survival

“…However, for reasons already discussed above, our results are difficult to compare with findings of previous investigations. All studies performed by means of computer-aided image analysing systems [11,28,51] showed a significant correlation of various AgNOR parameters with steroid hormone receptor expression and tumor grade. This could be confirmed in the present study.…”

Prognostic impact of proliferation-associated factors MIB1 (Ki-67) and S-phase in node-negative breast cancer

“…Biesterfeld et al (1995) showed that MFC had a greater prognostic impact than the Bloom-Richardson score in their series of 104 ductal breast carcinomas. Data concerning correlations between Ki-67 and other cell kinetics markers in breast cancer are controversial: a significant correlation to argyrophilic nucleolus organizing regions (AgNOR) has been reported (Dervan et al, 1989;Ruschoff et al, 1990); however, no significant correlation between Ki-67 and the proliferating cell nuclear antigen (PCNA) has been found (Gasparini et al, 1994). For Ki-67 as well as Sphase fraction, a significant correlation with the thymidine labelling index has been reported (McDivitt et al, 1986;Kamel et al, 1989).…”