Currently used diagnostic criteria in different endemic (Balkan) nephropathy (EN) centers involve different combinations of parameters, various cut-off values and many of them are not in agreement with proposed international guidelines. Leaders of EN centers began to address these problems at scientific meetings, and this paper is the outgrowth of those discussions. The main aim is to provide recommendations for clinical work on current knowledge and expertise. This document is developed for use by general physicians, nephrologists, urologist, public health experts and epidemiologist, and it is hoped that it will be adopted by responsible institutions in countries harboring EN. National medical providers should cover costs of screening and diagnostic procedures and treatment of EN patients with or without upper urothelial cancers.

Proto-oncogenes, growth factors/receptors, and tumour suppressor genes were analysed in malignant metastatic insulinomas. Normal pancreas showed only a moderate immunoreaction for c-myc proto-oncogene and a strong reaction for insulin. Benign insulinomas were slightly or moderately positive for transforming growth factor alpha (TGF alpha), weakly positive for epidermal growth factor receptor (EGF-R), and strongly positive for c-myc and insulin. In malignant insulinomas, besides a strong immunoreaction for c-myc and TGF alpha, activation of c-K-ras and overexpression of p53 protein were found. Insulin reaction was moderate or strong. Three out of six malignant insulinomas displayed a c-K-ras point mutation at codon 12. All mutations were guanine to cytosine transversion, resulting in amino acid substitution, glycine to arginine. Mutations were present in metastatic insulinomas only. Patients with mutated c-K-ras oncogene had overexpression of p53 protein as well as c-myc and TGF alpha overexpression. Our results support the view that malignant progression is a consequence of more than one genetic lesion and suggest that activation of myc, TGF alpha an ras genes plays a role in a multistep process of tumour progression, perhaps serving as an initiating event.

The aim of this study was to analyse relationship between changes of the stroma and expression of tenascin-C (TN-C) and laminin in prostate carcinoma. Tenascin-C immunostaining was increased, and laminin decreased in carcinomas compared with peritumoural tissue and benign prostate hyperplasia (Po0.05). Statistical analysis confirmed connection between stromal changes and TN-C expression in prostate carcinoma (Po0.05). Gleason pattern 3 carcinomas showed more pronounced stromal reaction and TN-C expression compared with Gleason pattern 4 carcinomas (Po0.05). The main cells in prostate cancer stroma are myofibroblasts that are also responsible for tenascin production. Degradation of laminin was not connected with myofibroblastic stromal changes.

The diagnosis of prostatic adenocarcinoma in needle core biopsy is based on major and supportive criteria. One of the supportive criteria is the presence of retraction clefting around neoplastic glands. We analyzed a series of 137 prostatic cancer cases diagnosed by needle core biopsy to determine the frequency, extent and criteria for periacinar retraction clefting. Clefting was analyzed on ten neoplastic and ten normal glands in three different high power fields. One-third or more glands with clefts affecting more than 50% of circumference were significantly more common in tumors (51.8%) than in benign glands (8%) (P<0.0001). A stricter criterion that designated as positive the cases with at least 50% of neoplastic glands (15 of 30) with clefts that affected more than 50% of circumference revealed clefts in only 15.3% of the malignant cases but none in benign cases (0%) (P<0.0001). Regardless of their extension, 15 or more glands with clefts were also more prominent in malignant cases (86.9%) than in benign cases (20.4%) (P<0.0001). We conclude that periacinar retraction clefting represents a reliable criterion for diagnosis of the prostatic adenocarcinoma, especially in cases with clefts affecting more than 50% of circumference in at least 50% of suspicious glands.

According to novel investigations, actinic keratosis (AK) is not a premalignant lesion but is a malignant lesion in the evolution to invasive squamous cell carcinoma (SCC). Thus, we analyzed p53, bcl-2 and growth hormone receptor (GHR) expression in hypertrophic-type AK (HAK) to determine the relative importance of these protooncogenes in the biological behavior of HAK. Expression of p53, bcl-2 and GHR was determined by immunohistochemistry in 33 HAK specimens and surrounding perilesional normal skin (PNS). The relative proportions of immunoreactive cells were determined. Of the 33 HAK specimens, 30 (91%) showed immunopositive staining for p53, 33 (100%) for bcl-2, and 12 (36%) for GHR. Highly positive p53 expression in HAK lesions could indicate that p53 mutation is an early and crucial event in lesion development. The detected pattern of the p53/ bcl-2 ratio in HAK suggests an important role for another gene: the proapoptotic gene bax. Our findings indicate that GHR expression could be a biological marker of progression of HAK to SCC.