In the present study we investigated the expression of the ERBB2 protein and neurofibromin in human benign and malignant Schwann cell tumors, traumatic neuromas and peripheral nerves without pathological findings. By immunohistochemistry and Western analysis ERBB2 expression was not detectable in normal nerves but in proliferating Schwann cells of traumatic neuromas. While none of the malignant schwannomas exhibited ERBB2 expression, weak expression was seen in a small proportion of the benign schwannomas. Low levels of neurofibromin were detectable in normal nerves but not in traumatic neuromas or tumors. These data indicate an inverse expression pattern of ERBB2 and neurofibromin in human non-neoplastic Schwann cells, but not in neurinoma cells.

The expression of two specific nucleolar antigens, p120 and B23, has been investigated in the prostatic carcinoma cell line LNCaP as well as in 40 frozen and 40 formalin-fixed tissue samples of benign and malignant prostatic lesions (15 benign hyperplasias, 5 grade 1, 15 grade 2, and 5 grade 3 carcinomas). In vitro, immunoreactivity of p120 was confined to nucleoli of proliferating cells, with virtually no negative staining during S and G2/M phases. Unlike p120, B23 was expressed in the nucleoli of all LNCaP cells independently of growth and cell cycle phases. Hence, B23 was detectable in all stromal as well as in normal and malignant epithelial prostatic cells, both in fresh and in formalin-fixed tissue sections after microwave treatment. In contrast, the immunoreactivity of p120 was almost completely restricted to the nucleoli of prostate carcinoma cells: frozen sections of benign prostatic hyperplasia (n = 15) were either totally negative for p120 (n = 13) or had a low percentage of positively stained cells (labeling index = 3.3% in 3 cases). In the carcinoma group 76% (19/25) of the specimens were p120 positive, and there was a significant rise of labeling index from 18.1% in grade 1 to 82.2% in grade 3 carcinomas (P < 0.001). In contrast to B23, p120 could not be reliably demonstrated in formalin-fixed and paraffin-embedded tissue. We therefore conclude that anti-B23 is a general marker of nucleoli, whereas expression of p120 appears to correlate with "hyperactivity" of the nucleolus and provides a new tool for flow cytometrical and immunohistochemical assessment of nucleolar activity in tumor pathology.

Silver staining of nucleolar organizer regions (AgNORs) is now widely used as a marker of malignancy in tumor pathology. Standardization of the AgNOR technique has thereby been shown to be of central importance. Basically, three types of AgNOR evaluation have been used: the counting method, image analysis and pattern recognition. Today, image analytical determination of AgNOR area per nucleus is considered to be the state of art method of AgNOR evaluation. In contrast, counting of every single AgNOR dot is laborious and less reproducible. For routine purposes, however, a rapid evaluation of AgNORs would be desirable. In order to elucidate the value of AgNOR distribution patterns systematic in vitro studies using four different urothelial cell lines (HU609, RT4, J82, MGHU1) were performed. AgNOR number (NORN) and AgNOR area (NORA) were closely related to the population doubling time (PDT) and increased during transition from G0/G1 to S/G2 cell cycle phase. In addition, both parameters were significantly elevated in the polyploid RT4 cell line. In contrast, number and area of AgNOR cluster (aggregates of at least two AgNOR dots) were less significantly correlated to PDT. Formation of large AgNOR clusters (maximum diameter over 6 microns) was, however, restricted to the well differentiated cell lines (HU609, RT4) although PDT was almost identical in all 4 cell lines at exponential growth phase. Thus, NORN and NORA are not only related to cell proliferation but also to cell cycle phases and ploidy.(ABSTRACT TRUNCATED AT 250 WORDS)