Immunohistochemical characterization of urothelial carcinoma.

From the archive of BB Biocyt company, 32 urinary bladder carcinomas (urothelium carcinomas, UC) and 7 cases of chronic cystitis were selected and examined in semiserial sections for the following antigens: 1) cell proliferation marker Ki-67 (expressed in the nuclei), 2) cell cycle regulator p16/INK4a polypeptide (expressed in the cytoplasm and nuclei), 3) urothelium marker p63 (expressed in the nuclei), 4) cytokeratin 7 (CK7). 5) cytokeratin 20 (CK20) and 6) high molecular weight cytokeratin (HMWCK). Invasive urothelium carcinomas showing a high grade dysplasia (invasive HG UC) comprised over the half (20 out of 32) of the investigated tumours. Microinvasion to lamina propria (seen in three HG papillary carcinomas) was regarded as an early infiltration even when the position of muscular layer could not be determined. Classical invasion across the urinary bladder wall and/or to surrounding tissues was found in 17 cases of low-differentiated HG UCs. The rest (9 out of 32 neoplasms) were either non-invasive papillary carcinomas of high (non-invasive HG UC, 5 cases) or low malignant potential (noninvasive LG UC, 4 cases). Finally, 3 cases were papillary urothelium neoplasms of low malignant potential (PUNLMP). HMWCK was present in all invasive tumours, whereas the frequency of other urothelium markers ranged from 65 to 88 %. Nevertheless, at least two markers were expressed in each invasive tumour. Staining for Ki-67 antigen was positive in over 50 % of the nuclei of HG UCs, while in the LG UCs, the frequency of positive Ki-67 staining did not exceed 25 %. In PUNLMP, the positive rate of Ki-67 stained dysplastic cells was below 10 %. The staining for p16 antigen did not correlate with the degree of dysplasia within urothelium tumours. For routine diagnostic, we recommend to combine the Ki-67 staining with detection of HMWCK. In cases of chronic cystitis, which developed urothelial hyperplasia and/or squamous metaplasia, the presence of p63 antigen was a relevant marker confirming the urothelial origin of the altered transitional cells (Tab. 6, Fig. 4, Ref. 69).

[Detection of regulatory protein p16/INK4A in the dysplastic cervical squamous cell epithelium is a diagnostic tool for carcinoma prevention]. / Detekcia regulacného proteínu p16/INK4A v dysplastickom dlazdicovom epiteli krcka maternice ako diagnostický nástroj prevencie karcinómu.

Parallel sections from 423 randomly selected blocks representing biopsies of 178 women with the diagnosis of cervical dysplasia and/or erosion were stained for p16 polypeptide. The p16/INK4A (inhibitory kinase 4) protein is a cellular division regulator, expression of which increases in the presence of oncoprotein E7, encoded by human papillomavirus (HPV). Expression of p16 protein was seen in the nuclei and cytoplasm of dysplastic squamous epithelium cells as well as in carcinoma cells. In 16.6% of erosion cases, the p16 antigen was present in the basal and suprabasal layer of the surrounding squamous epithelium revealing features of CIN I/LSIL. In CIN I/LSIL as classified by HE staining, the p16 antigen was found in 65 out of 80 (81%) cases. The p16 protein was typically seen in dysplastic basal and suprabasal cells encompassing a confluent layer in the lowest third segment of stratified epithelium. In CIN II and CIN III grouped as HSIL, the positive rate of p16 antigen presence was 95% (in 45 cases out of 47) and/or 100% (in each of 27 cases), respectively. The typical sign of p16 antigen distribution in HSIL was its staining over two thirds and/or throughout the whole dysplastic epithelium. Extensive staining for p16 antigen was registered within nuclei as well as cytoplasm of neoplastic cells in all 6 cervical squamous cell carcinomas, which were examined in many sections when being used as positive controls. Based on our experience, we consider the p16 antigen staining a helpful tool indicating dysplastic cells and estimating their extent.

[Deep soft-tissue leiomyoma]. / Leiomyóm hlbokých mäkkých tkanív.

Deep soft tissue leiomyomas (DSTL) are very rare. For this reason they are neither histologically, nor clinically reliably characterized, especially regarding their dignity. The authors present two cases of leiomyomas which grew from the deep soft tissue in the region of the head and perineum. Both cases involved women 43 and 63 years of age. Characteristically morphological traits, as e.g. good borderline of lesion, the presence of fibrous pseudocapsule, and classical morphologic appearance of leiomyoma were present in both cases. While in the first case the foci of dystrophic calcification within regressively altered foci of the tumour were found, the second case involved the presence of foci of myxohyalin degeneration of stroma. The first tumour contained also parts with a palisade arrangement of nuclei which gives a hint of resemblance to that of neurilemmoma. Mitoses did not exceed the HPF index of 2/10 in neither of the cases. Both cases were S-100 immunohistochemically negative, actin and human muscle actin were significantly positive, desmin was weakly or mediately positive, and vimentin significantly or mediately positive. The first case involved a clinical recurrence of a histologically verified leiomyoma after 5 years in the same location with MI being of zero value. Regarding the presented characteristics, the authors classify the described leiomyomas as DSTL. These tumours with an uncertain prognosis can metastatize despite their benign morphology. (Tab. 2, Fig. 4, Ref. 19.)