Prognostic significance of the proliferative activity in neuroblastoma.

The prognostic significance of the immunohistochemically assessed growth fraction in neuroblastomas was determined in relation to tumor grade and tumor stage. A total of 101 cases of neuroblastoma were examined with the monoclonal antibodies PC10 against proliferating cell nuclear antigen (PCNA) and Ki-S5 against the Ki-67 protein. Patients were followed for a mean time of 4.8 years. Expression of both PC10 and Ki-S5 was found to be significantly linked to tumor grade and tumor stage. Prognostically favorable stage IVs was associated with low PCNA and Ki-S5 levels. For ganglioneuroblastoma, significant differences were found between the diffuse and the composite type. In univariate analysis of stage III and IV tumors, Ki-S5 and PCNA scores were significantly correlated with disease-free survival (P < 0.0015), allowing definition of a subset of cases with favorable outcome. As to Shimada's group with poor prognosis, significant differences in the clinical course were found for low and high Ki-S5 scores (P = 0.036) but not for PCNA. In multivariate analysis, only patient age, Shimada's grade, and Ki-S5 scores achieved prognostic significance. We conclude that proliferation marker Ki-S5 may provide substantial prognostic information and might become a useful adjunct for predicting the clinical courses of neuroblastoma.

Diagnostic assessment of two novel proliferation-specific antigens in benign and malignant melanocytic lesions.

The aim of this study was to gain a thorough insight into the proliferative activity of benign and malignant melanocytic tumors. A total of 314 cases were examined by immunohistochemistry on paraffin-embedded material. The growth fraction was assessed by means of two monoclonal antibodies, Ki-S1 and Ki-S5, which react with two different proliferation-specific nuclear antigens. Additionally, HMB-45 was used as a marker of melanocytic activation. Statistically significant differences (P < 0.01) in the proliferation rates were found between common acquired nevi, Spitz's/Reed's nevi, primary cutaneous melanomas, and metastatic melanomas, whereas dysplastic nevi were hardly distinct from other nevi of the compound type. In melanoma, the growth fraction correlated well with the tumor stage but poorly with HMB-45 expression and mitotic count. Along with tumor progression, an increasing heterogeneity of proliferation indices was observed. Our results provide no evidence for a progression from dysplastic nevi into melanoma. They indicate that the assessment of the proliferative activity may be of considerable diagnostic help in cases of uncertain histology and that it might contribute to an alternative concept for the classification of melanocytic tumors.

Expression of CD30 and nerve growth factor-receptor in neoplastic and reactive vascular lesions: an immunohistochemical study.

A total of 118 biopsies from 20 different types of benign, malignant and reactive vascular proliferations were examined for the expression of the CD30 antigen using the monoclonal antibodies BerH2 and HRS4 on paraffin-embedded sections. The results were compared with those obtained using an antibody directed against the partially homologous nerve growth factor-receptor. The vascular character of the lesions was assessed by means of endothelial markers and the expression of intermediate filaments was verified immunohistochemically. CD30 was expressed in the endothelial component of more than the half of all tumours, with the exceptions of Kaposi's sarcoma and teleangiectatic granuloma. There was a slightly higher rate of Ki-1 positivity in malignant lesions. Nerve growth factor-receptor could be demonstrated in a similar percentage in both endothelium and pericytes, but no correlation with CD30 could be established. We conclude, therefore, that these antigens are not adequate for the differential diagnosis of vascular lesions, nor do they help distinguish between benign and malignant lesions. Their expression seems to reflect different states of cellular function or activation. It does not necessarily occur simultaneously or in the same cell type.

[Determination of proliferation activity of prostate cancers by means of nuclear proliferation-associated formalin resistant Ki-S5 antigens]. / Bestimmung der Proliferationsaktivität von Prostatakarzinomen anhand des nukleären Proliferations-assoziierten formalinresistenten Ki-S5 Antigens.

In order to evaluate the growth fraction in normal, hyperplastic and neoplastic prostatic tissue, we examined paraffin sections of 55 cases of prostatic cancer containing areas of benign (BPH) and atypical hyperplasia (AH). Cellular proliferation was assessed by nuclear staining with the monoclonal antibody Ki-S5 directed against a formalin-resistant epitope of the Ki67 antigen. The proliferation rate was minimal in normal glands and BPH (mean 0.35%), rather low in AH and grade I carcinoma (0.5 to 15% compared to grade II carcinoma (1 to 40%) and peaking to near 80% labeled cells in grade III carcinoma. In the majority of the tumors, foci of increased cell growth could be detected by this method. Ki-S5 labeling indices correlated significantly with the histopathologic grading established by Dhom. Correlation with the clinical outcome will be the subject of subsequent retrospective studies.