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Aims and background The p53 protein is essential for the regulation of cell proliferation and its aberrant accumulation is usually seen in malignant tumors but also occurs in squamous epithelium of inflammatory skin diseases characterized by hyperproliferation. The aim of this study is to elucidate the role of the p53 tumor suppressor protein in the pathogenesis of different hyperproliferative, non-malignant and malignant skin diseases, and to determine the association between p53 overexpression and cell proliferation. We also investigated the influence of aging on p53 and Ki-67 protein expression.Methods One hundred and fifty skin specimens divided into 30 samples each of normal skin (NS), psoriatic skin (PS), keratoacanthomas (KA), basal cell carcinomas (BCC), and squamous cell carcinomas (SCC) were examined immunohistochemically to assess p53 and Ki-67 protein expression.Results p53 immunostaining of NS, PS, KA, BCC and SCC was detected in 39.0%, 46.7%, 66.7%, 80% and 86.7% of cases, respectively. Median values and ranges of p53 protein expression were as follows: 0.0% (range, 0.0–1.8%) in NS, 0.0% (range, 0.0–6.5%) in PS, 9.2% (range, 0.0–24.0%) in KA, 19.3% (range, 0.0–48.1%) in BCC and 30.1% (range, 0.0–68.1%) in SCC. p53- and Ki-67-positive cells were present in basal (NS) and suprabasal layers (PS), and not only in cancer nests of KA, BCC and SCC but also in dysplastic and even morphologically normal epidermis adjoining cancers. The positivity of p53 and Ki-67 proteins differed significantly among the groups, with no differences in p53 expression between NS and PS and in Ki-67 expression between PS and KA. Within all groups there was a significant correlation between p53 and Ki-67 expression. Lesion location and patient age, with the exception of location in PS and age in BCC, were significantly related to p53 and Ki-67 expression in all groups.Conclusions Our findings suggest that p53 overexpression occurs mainly in neoplastic skin lesions, although it may also occur in squamous epithelium of inflammatory skin diseases such as PS, as well as in normal skin epithelium. It is associated with cell proliferation in normal as well as altered epithelium. p53 protein overexpression is an age-related process and significantly associated with sun exposure, especially in NS and PS but also in KA and SCC. Our findings suggest that Ki-67 rate and p53 protein expression reflect the degree of malignancy in the examined cutaneous neoplasms.

Immune system maturation proceeds postnatally in humans. Therefore, newborns, especially those of a lower gestational age, are not fully immunocompetent and are more likely to acquire perinatal infections. In order to investigate the neonatal immune system status, the major lymphocyte subpopulations were studied in newborns of different gestational age, comparing term newborns and adults.

Aims and background Breast carcinoma is a heterogeneous disease, the prognosis of which correlates with various prognostic factors. The aim of this study was to assess the prognostic significance of c-erbB-2 overexpression in breast carcinoma patients in association with other known prognostic factors.Methods & study design The relationship between immunohistochemical expression of the c-erbB-2 oncoprotein and various established prognostic factors such as tumor size, axillary node status, estrogen and progesterone receptor status, DNA ploidy, proliferation index, cathepsin D expression and histological grade in invasive ductal breast carcinoma is presented in this study.Results Of the 93 ductal invasive carcinomas 22 (23.7%) were grade I, 51 (54.8%) grade II, and 20 (21.5%) grade III, and the majority (78: 83.9%) were 2-5 cm in diameter. Tumor metastases were identified in one or more lymph nodes in 55 (59.1%) patients, the remaining 38 (40.9%) patients being lymph node negative. According to the DNA histograms 40 (43.0%) tumors were aneuploid and 53 (57.0%) were diploid, and the majority of tumors had more than 4% of cells in the S phase of the cell cycle (83.9%). Expression of c-erbB-2 as shown by immunohistochemical intense membrane staining was present in 49 (52.7%) tumors. Cathepsin D-positive cytoplasmic granular staining and cathepsin D-positive stromal macrophages were found in 60 (64.5%) and 72 (77.4%) tumors, respectively. Univariate analysis showed that overall survival correlated significantly with axillary lymph node involvement and with estrogen and progesterone receptor status for each of the receptors separately and for their coexpression, and only marginally with c-erbB-2 overexpression. In mulitivariate analysis only axillary lymph node metastases and coexpression of estrogen and progesterone receptors were found to be independent and significant prognostic factors.Conclusions When patients were stratified according, to c-erbB-2 expression it was shown that those with c-erbB-2 overexpression and grade II tumors, tumor size greater than 2 cm, high content of aneuploid cells and cathepsin D-positive stromal macrophages had a shorter long-term survival than c-erbB-2 negative patients.

Flow cytometric cell cycle analysis was performed on paraffin-embedded blocks from 49 patients with stage I endometrial carcinoma. Care was taken to separate tumor tissue from normal tissue in each specimen; normal tissue was used as a control for each individual specimen. DNA index, proliferative activity, and cell DNA aneuploidy were correlated with known parameters of tumor malignancy. Increased DNA index corresponded well with the DNA aneuploid tumors, poor tumor differentiation (G3), myometrial invasion of more than one-third, more malignant histologic type of tumor, and low concentration of estrogen (⩽10 fmole/mg) and progesterone (⩽25 fmole/mg) receptors. Similar results were obtained for tumor cell proliferative activity (percentage of cells in S + G2/M phases) and for DNA aneuploid tumors. Since more than 90% of patients with stage I endometrial carcinoma survived the 5-year postoperation period, analyzed parameters could not be checked for survival-related prognostic significance. However, our data indicate that cell cycle analysis may be instrumental for objective ranking of several known prognostic parameters.

Cytochemical analysis of leukemic blasts from 46 patients with acute myeloblastic M2 leukemia (according to the FAB classification) was performed before and after cytostatic therapy, and compared with findings obtained in 20 age- and sex-matched control subjects. Cytochemical findings for myeloperoxidase (MPO), Sudan black B, acid phosphatase and alpha-naphthyl-acetate esterase (ANAE) were related to the achievement of the first complete remission (CR),i.e.data were compared after the patients had been divided into CR and non-CR groups. The analysis clearly showed that a high proportion of myeloperoxidase- and, to a lesser extent, Sudan black B-positive blasts before treatment may have constituted a significantly unfavourable prognostic factor.

We have studied the correlation of two methods(immunohistology and ELISA in cytosol) of cathepsin D(CD) determination in breast carcinoma patients. Fifty sixspecimens of tumor tissue were collected consecutively, andCD expression in tumor tissue and tissue macrophageswas determined by standard immunohistochemistry using the aNCL-CDmanti-cathepsin D mouse monoclonal antibody (Novocastra Laboratories Ltd.,Newcastle, UK). Additionally, CD concentration was determined byELISA in cytosol of the same breast carcinomaspecimens. CD positivity was correlated with tumor size,histological grade of tumor, and the cytosol progesteroneand estrogen receptor concentrations. There was no statisticallysignificant correlation between examined parameters and either CDpositivity by immunohistochemistry or cytosol CD concentration. Thecorrelation between CD expression in tumor cells ofbreast carcinoma by immunohistochemistry and cytosol CD positivitywas not found either. However, there was asignificant association between abundance of CD positive stromalmacrophages and cytosol CD concentration in all histologicaltumor types (p < 0.05). CD positive macrophageswere abundant in most of cytosol CD positivespecimens.These results suggest that breast cancer cytosol CDconcentration is the cumulative result of CD contentin both carcinoma cells and stromal macrophages.