Our group has been studying the progressive molecular changes in prostatic epithelium which precede the invasive phenotype. Initial studies revealed similar alterations in cytoskeletal proteins between high grade prostatic intraepithelial neoplasia (PIN) lesions and invasive carcinoma. Specifically we observed an increased expression of certain cytokeratins and decreased expression of vimentin. We also noted a change in glycosylation as detected by Ulex europaeus staining. Using the latter technique we were able to microdissect and isolate nuclei from areas of low and high grade PIN lesions as well as from invasive carcinoma for morphometric analysis. Similarities in nuclear size, chromatin heterogeneity, and nuclear DNAcontent between low and high grade PIN and invasive carcinoma in carcinomatous specimens were noted. In contrast, these parameterswere significantly different in lowgrade PIN lesionsobtained from benign prostatic transurethral resection (TURP) specimens. In addition, DNA histograms revealed similar proliferative indices between high grade PIN and invasive carcinoma, which differed significantly from low grade PIN. Parameters thought to be relative to the invasive phenotype were also examined, such as the members of the rnetalloproteinase family; although normal luminal cells fail to express detectable levels of these enzymes, invasive carcinoma and even low grade PIN lesions express both the 72 kDa and 92 kDa type IV collagenase. Taken together, these data indicate that the dysplastic cells of PIN lesions and carcinomas are similar in nuclear and genomic features as well as protease expression. Our current working hypothesis is that these cells are already armed with the necessary proteases to invade the basal lamina but in an inactive form. Tumor progression requires an additional event of protease activation. The exact relationship of PIN lesions to invasive carcinoma remains unknown, however. PIN lesions are found in the peripheral prostate lobe 131, are multifocal [6,71, and when high grade are often found in association with invasive carcinoma [5,7]. Thymidine labelling studies have shown increased labelling of PIN when compared with simple prostatic hyperplasia 181.A number of recent immunohistochemical studies have shown progressive loss of markers of prostatic glandular secretion in the PIN lesions, implying a loss of glandular differentiation [9-131. We have examined the intermediate

Gal-3 might play a role in melanoma progression and/or inflammation, and warrants further study.

Material

The chromatin patterns of Feulgen-stained nuclei in a series of six specimens of normal mucosa and 331 transitional bladder carcinomas, including 293 superficial (Ta and T1) and 38 invasive (T2-T4) cases, were quantitatively described by means of eight parameters relating to densitometric, run-length distribution, and co-occurrence matrix features. The results show that the chromatin texture of the superficial lesions was markedly different from that of the invasive tumours, which exhibited a distinctly more dense and heterogeneous chromatin pattern. The data also show that the increasing level of malignancy, as revealed by the increasing clinical stage, was accompanied by an increase in the overall chromatin condensation level. Only some areas of the nucleus actually increased in density; other pale areas appeared concomitantly with these increasingly denser chromatin areas. This chromatin density increase corresponded to a marked increase in the frequency of small dense chromatin clumps; these joined together into very large dense chromatin clumps, which were distributed more and more heterogeneously in the nucleus as the clinical stage of the tumour increased.

Quantitative measurements of the collagen types (I, II, and IV) in the corpora cavernosa of potent and impotent men were carried out to investigate whether quantitative immunohistochemistry might contribute additional information as to the cause of erectile dysfunction. The study group consisted of 22 men with various etiologies of impotence and 4 normal, potent men. The quantitative immunohistochemistry measurements were performed by means of a cell-image processor. Three variables for each of the three types of collagen were studied, namely, the mean optical density (MOD), which relates to histochemical staining intensity; the labeling index (LI), which is positively related to the percentage of immunostaining; and the quick score (QS) index, which takes into account both LI and MOD values. None of the quantitative parameters taken individually (monovariate statistical analyses) made it possible to obtain any statistically significant difference between the types of collagen of the group under study. The mean QS value recorded for collagen type IV was significantly lower than that noted for collagen type I in the psychogenic (P = 0.019), arteriogenic (P = 0.012), and venogenic (P = 0.001) groups, whereas the MOD value was significantly lower in the normal (P = 0.043), arteriogenic (P = 0.013), and venogenic (P = 0.001) groups but not in the psycogenic group. The mean MOD of collagen type III was intermediate between that of the other types. In contrast, the mean LI value recorded for collagen type IV was significantly lower only in the venogenic (P = 0.032) and psychogenic (P = 0.049) groups as compared with the other groups. No objective qualitative change in the collagen types was observed that could be correlated to the etiology of erectile dysfunction. The significant difference seen in the quantitative parameters with regard to collagen type IV and the observed increase in the type I/III collagen ratio might attest to the notion that the response of the erectile tissue to ischemia is similar to that of other organs. The net effect of these changes is a restricted capacity for corporal expansion and alteration of the veno-occlusive mechanism.