Abstract. The presence of androgen receptors (AR) in neuroendocrine cells was investigated in benign tissue of 10 prostatectomy specimens, in 12 prostatic adenocarcinomas with focal neuroendocrine differentiation and in 1 case of a pure neuroendocrine small cell carcinoma of the prostate. Neuroendocrine cells were defined by their reactivity with an antibody to chromogranin A. Monoclonal antibody F39.4 directed against the amino-terminal domain of the AR molecule was used to detect AR. AR and chromogranin A were simultaneously visualized with a double immunofluorescence technique. The results indicate that chromogranin positive cells in both benign and malignant prostatic tissue lack detectable expression of AR. No effect of endocrine therapy was noted. These results are in agreement with the hypothesis that prostatic neuroendocrine tumour cells represent an androgen insensitive cell population, which incidentally may expand to replace the androgen-sensitive tumour cell population during androgen ablation therapy.

We describe the immunohistochemical detection of the human androgen receptor (AR) in routinely p d , pataffinembedded tissue with the monoclonal antibody (MAb) F39.4. Deparaffrnized d o n s were heated in a microWave oven for antigen retrieval. A panel of human male-and female-derived tissues was investigated. We observed a nuclear staining pattern consistent with previous results on frozen sections. Moreover, we studied the possibility of detecting AR in prolonged formalin-fmed tissue and in paraffin-embedded archival m a t e d . After prolonged fmhtroduction Androgens play an important role in the development and function of the male reproductive system. They mediate their function by binding to the intracellular androgen receptor (AR). Studies on AR distribution in human reproductive and non-reproductive tissues may provide essential information about its role in disease processes that arise in tissues which express the AR.Over the past years, AR distribution in human tissues has been the subject of many immunohistochemical studies (2,4,7,10,13,17). Both polyclonal and monoclonal antibodies (MAb) directed against human AR have been used to visualize the receptor at the cellular level. U e d a et al. (17) studied the immunohistochemical localization of the AR in frozen sections of different tissues, using both MAb and polyclonal antibodies. Ruizeveld de Winter et al. (13) used MAb F39.4 to study AR expression in frozen sections of different human tissues. Kimura et al. (7) investigated the immunohistochemical localization of the AR in paraformaldehyde-fixed, paraffin-embedded human tissues with a polyclonal antibody. In the latter study, decreased or absent immunoreactivity was found (12) studied the immunohistochemical identification of the AR in germ cell neoplasia using MAb ANI-15 and F39.4 on frozen and formalin-fixed tissue. Both antibodies showed a positive reaction on frozen sections. However, on paraffii sections, MAb F39.4 showed no reaction and MAb ANI-15 showed strong nuclear immunoreactivity of all testicular nuclei including lymphocytes, suggesting the possibility of a nonspecific reaction. Recently, Nakada et al. (11) were able to detect the AR in neuroendocrine cells in Amexprocessed (14) but not in formalin-fixed, paraffin-embedded human prostate tissue with MAb AN1-15.Until recently, to our knowledge, it has been impossible to detect the human AR in routinely formalin-fixed, paraffin-embedded tissue with an MAb. This is of great advantage because of the highly consistent specificity of MAb in combination with the optimal morphology achieved in paraffii sections and the possibility of reuospective studies. The present study describes the detection of human AR with MAb F39.4 in routinely formalin-fued, paraffin-embedded tissue, after a simple antigen retrieval treatment (16). A panel of human male-and female-derived tissues was investigated for the presence and distribution of the AR. The results were compared 1169

Androgen deprivation leads to an upregulation of stromal ER expression in human prostate. Estrogen-induced morphological epithelial changes could be explained by a paracrine interaction between stromal and epithelial cells.

Large gemistocytic cells are well-known elements of glial tumors. Recently, miniature gemistocytic cells and neoplastic glial fibrillary acidic protein (GFAP)-positive oligodendroglial cells, which are regularly seen in oligodendrogliomas, have been termed "transitional cells". The proliferative activity of the gemistocytic cell types and the GFAP-positive (gliofibrillary) oligodendrocytes was determined in eight astrocytomas, seven gemistocytic astrocytomas, eight glioblastomas, two monstrocellular glioblastomas, seven oligodendrogliomas and three mixed oligo-astrocytomas by immunohistochemical staining of the proliferation marker MIB-1 in combination with immunostaining for GFAP. Both large gemistocytic cells and the transitional cells showed cytoplasmic GFAP-positive staining. Neither in the classic gemistocytes nor in the minigemistocytes nuclear immunostaining for the MIB-1 antibody was observed. In contrast, MIB-1 staining was seen in the gliofibrillary oligodendrocytes. It is concluded that both large and miniature gemistocytic cell types contrast with gliofibrillary oligodendrocytes by their inability to proliferate.

Over the last two decades nonradioactive nucleic acid labeling and detection systems have overcome the safety, disposal, stability and cost problems that are associated with radioactive techniques. Besides traditional, enzyme-mediated, nonradioactive labeling methods (e.g., random priming, nick translation or labeling by PCR), several chemical labeling systems have been developed (e.g., ULS, psoralen, alkylating agents). These methods provide fluorescent (or hapten) labeled probes for fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH) and microarray-based techniques. In this review the DNA-based molecular diagnostic applications and perspectives of the Universal Linkage System (ULS) technology will be described.

Androgen deprivation leads to an upregulation of stromal ER expression in human prostate. Estrogen-induced morphological epithelial changes could be explained by a paracrine interaction between stromal and epithelial cells.

SummaryNine 'carcinoids' of the breast (argyrophilic carcinomas) were examined for the presence of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR), using immunohistochemistry. The tumours were selected on the basis of their histo-morphological appearance and positive Grimelius stain. All cases were immunoreactive for neuron-specific enolase (NSE). In one case the tumour cells were intensely chromogranin A positive. All cases were E R positive, while 5 cases expressed A R and 5 cases PR. Immunostaining for E R and simultaneous demonstration of argyrophilia or chromogranin A expression in chromogranin A positive argyrophilic carcinoid tumour of the breast provided further evidence that neuroendocrine cells in breast tumours express sex steroid receptors. The similarity in sex steroid receptor expression pattern in 'carcinoids' of the breast and the more common categories of breast cancer suggests an identical responsiveness to endocrine therapy.