Professor Witold Nowicki - a greatly spirited pathologist.

This paper presents a complete overview of the scientific, professional and social activity of a great Polish pathologist, Witold Nowicki (1878-1941), from mainly Polish-written, original sources with a major impact on mostly his own publications. The biographical commemoration of this eminent professor is not only due to the fact that he provided a profound microscopic characterization of pneumatosis cystoides in 1909 and 1924. Nowicki greatly influenced the development of anatomical pathology in Poland, having authored over 82 publications, with special reference to tuberculosis, lung cancer, sarcomatous carcinomas, scleroma and others. However, the first of all his merits for the readership of Polish pathologists was his textbook titled Anatomical Pathology, which was a basic pathology manual in pre-war Poland. Witold Nowicki - as the head of the academic pathological anatomy department and former dean of the medical faculty - was shot with other professors by Nazi Germans in the Wuleckie hills in Lvov during World War Two. Professor Nowicki was described as being "small in size but great in spirit" by one of his associates, and remains an outstanding example of a meticulous pathologist, a patient tutor and a great social activist to follow.

Ancient cardiac myxomas - another point of view in the light of tetraspanins.

Myxomas are the most common non-invasive but life-threatening cardiac neoplasms due to obstruction of heart chambers and risk of embolism in a manner resembling thromboembolism as well. They can occasionally disseminate via their detached fragments into the bloodstream to seed and grow as secondary still benign tumors. In this study we evaluated morphological and clinical aspects of 14 ancient, degenerated left or right-sided cardiac atrial myxomas with expression of CD9 and CD63, which are found to contribute to platelet activation, aggregation and, as a result, intratumoral thrombosis or fragmentation. The appearance of tumors varied from sessile to polypoid revealing that a higher rate of endocardial thrombosis was associated with sessile compared to polypoid myxomas and left-sided tumors compared to right-sided ones in our study. In the general aspect of ancient calcifications, amorphous calcification with intra-tumor thrombosis was noted more frequently in sessile tumors, while well-formed osseous metaplasia was usually a feature of polypoid tumors. In our material osseous metaplasia did not coexist with massive thrombosis and was found in polypoid, pedunculated myxomas. Most importantly, CD9 overexpression was recorded in every studied myxoma and CD63 gave a weak reaction in myxoma cells.

Coexistence of mature cystic teratoma and adenocarcinoma in situ within atypical proliferative mucinous tumour of ovary--a case report of 35-year-old woman.

Combined ovarian tumors are found in common pathologic practice due to amazing potential of ovarian tissue to copy almost every tissue of human body and imitate many neoplasms of various other organs in a very flexible way. A multicystic tumor is presented in this case report of 35-year-old woman. It consisted of a cyst with sebum and hair and cavities with papillomatous projections and mucus. The ovarian tumor was diagnosed a mature cystic teratoma presenting mainly as dermoid cyst and mucinous adenocarcinoma in situ, arising within atypical proliferative mucinous tumor. This report demonstrates how histoformative properties are reflected in ovarian tumorigenesis. Such a stunning histoformativity makes ovaries the possible site of primary origin for malignant tumors that mimic extra ovarian differentiation. In the authors' point of view, the diagnosis of primary ovarian mucinous tumor within cystic teratoma is firm, whenever simultaneous extraovarian involvement by mucinous neoplasm is excluded.

Acardius acephalus fetus--report of distinctive anatomical anomalies with regards to pathophysiology of TRAP sequence.

Acardiac fetuses are consequences of twin reversed arterial perfusion (TRAP). Here the authors present a case of 40-year-old gravida IX who gave birth to a healthy, 2,900 g female child by a cesarean section. Additionally amorphic 1,020 g maldeveloped fetus was removed. There was a diamnion monochorionic type of twin placenta with incorrect single umbilical arteries (SUA) both in umbilical cord of healthy fetus and in atrophic second umbilical cord. A malformed fetus developed a rather well formed lower leg with four digital foot and oval shape amorphous body mass with omphalocele and eventration of the intestines. X-ray picture showed well visible metatarsal and femur bone and anatomically undefined bones cluster in the central part. A cavity of fetal body contained intestines--the only one well-formed organ, nests of heterotopic pilosebaceous residues, remnants of adrenal glands, well-formed ganglia, and nests of neural tissue covered by neuroepithelium.

Is there a place for practical chemoprevention of colorectal cancer in light of COX-2 heterogeneity?

COX-2 overexpression is widely recognized as an accidental and relatively important factor in the progress of colon neoplasia, but the practical significance of it has not yet been defined. As such, the purposes of the study were: an analysis of the changes of COX-2 expression within colon adenomas in the dependence of progress of dysplastic level within colon adenomas, the analysis of COX-2 expression in cryptal and superficial parts of polyp and, additionally, the analysis of the COX-2 heterogeneity between colon adenomas. One hundred and four cases with completely resected adenomas with high-grade epithelial dysplasia were included in the research. Each polyp had persistent low-grade dysplasia and normal colon mucosa at the base as an internal control. Immunohistochemical analysis with monoclonal COX-2 antibody was performed. Regression of COX-2 expression in high-grade colon intraepithelial lesions (HGCoIN) compared with low-grade colon intraepithelial lesions (LGCoIN) (p = 0.00001) was observed. No correlation between stromal COX-2 expression and either LGCoIN or HGCoIN was found (p > 0.05). The next important observation was a difference in superficial and cryptal COX-2 expression (p < 0.001) and the evident heterogeneity of COX-2 expression among adenomas at LGCoIN as well HGCoIN foci (p < 0.01). The regression of COX-2 expression in high-grade parts of adenomas which we described may result in a reduction of the role of chemoprevention by the use of NSAIDs.

Serum erythropoietin and angiogenetic factors in human colorectal cancer.

AIMS AND BACKGROUND: Erythropoietin, VEGF, VE-cadherin are involved in angiogenesis. Besides that erythropoietin stimulates erythropoiesis and increases haemoglobin and hematocrit levels as well. Moreover, erythropoietin could directly stimulate colorectal cancer cell growth due to the presence of both erythropoietin receptor and erythropoietin production in malignant cells of this neoplasm. Therefore we aimed at measurement and comparison of serum erythropoietin with VEGF, VE-cadherin levels, blood haemoglobin and hematocrit in colorectal cancer patients of different clinicopathological profiles. METHODS: We applied ELISA kits to evaluate preoperative serum levels of endogenous erythropoietin, VEGF and VE-cadherin in samples from 92 colorectal cancer patients and control group of 16 healthy volunteers. RESULTS: Endogenous erythropoietin was significantly elevated in preoperative sera in colorectal cancer patients (p = 0.013) compared with healthy volunteers, however, erythropoietin levels were not significantly higher with the advancement of colorectal cancer. There were significantly higher levels of erythropoietin in the group of anaemic men in comparison to men with normal haemoglobin levels (p < 0.0001). VEGF and VE-cadherin did not correlate with erythropoietin. Erythropoietin levels negatively correlated with haemoglobin and hematocrit levels in all cancer patients; particularly in node positive cancers (N+), moderately differentiated tumours (G2) and deeply invading neoplasms (pT3+pT4). CONCLUSIONS: Erythropoietin levels increase in colorectal cancer but circulating erythropoietin does not associate with progression of the disease. Thus, the use of recombinant erythropoietin seems to be safe. Our results suggest that negative feedback regulation persists between haemoglobin and erythropoietin in colorectal cancer. Production of erythropoietin remains therefore anaemia-associated, hypoxia-dependent and doesn't seem to be autonomic despite abundant expression of erythropoietin by colorectal cancers.

Increased expression of connexins 26 and 43 in lymph node metastases of breast cancer.

BACKGROUND: Gap junctions are intercellular channels composed of connexins, which mediate the direct passage of small molecules between neighbouring cells. They are involved in regulation of cell cycle, cell signalling, and differentiation, and probably invasion and metastasis. The role of connexins in the metastatic process is controversial, because some studies indicate that connexin expression is inversely correlated with metastatic capacity. In contrast, others demonstrate that connexins may be involved in metastasis. In addition, connexin status in breast cancer metastasis has not been widely studied. METHODS: We evaluated by immunohistochemistry the expression of connexin 26 (Cx26) and connexin 43 (Cx43) in primary breast tumours (PTs) and matched paired metastases to lymph nodes (MLNs). RESULTS: In PTs, we observed predominantly cytoplasmic localisation of evaluated connexins, indicating alterations in connexin expression in breast cancer cells. We demonstrated that expression of Cx26 and Cx43 was increased in MLNs compared with PTs (p<0.00001 and p<0.001, for CX26 and Cx43, respectively). In addition, Cx26 and Cx43 negative PTs developed Cx26 and Cx43 positive MLNs. Furthermore, besides increased cytoplasmic staining, enhanced membranous localisation of Cx43, typical of normal cells, was found in MLNs. Additionally, membranous Cx26 expression appeared only in metastatic breast cancer cells. CONCLUSIONS: These findings suggest that connexins may contribute to the efficient metastasising of breast cancer to the lymph nodes.

P53 correlates positively with VEGF in preoperative sera of colorectal cancer patients.

Diversity of P53 impact on tumor angiogenesis is due to the fact that wild-type P53 decreases expression of vascular endothelial growth factor (VEGF), but mutant P53 upregulates it. Therefore, we aimed at uncovering relations between preoperative serum levels of VEGF and P53 in colorectal cancer (CRC) patients. Preoperative blood samples of 125 CRC patients and 16 control healthy volunteers were examined with an ELISA-kit for serum P53 levels and VEGF. P53 did not correlate with VEGF in the whole group of CRC patients. However, P53 associated with VEGF in case of colorectal cancer patients, whose serum values of VEGF were higher than in controls (VEGF{H} >5.9333 pg/ml) (r=0.274, p<0.009). We revealed a positive correlation between P53 and VEGF{H} in subsets of poorly differentiated (G3) cancers (p<0.02), lymph node positive (p<0.007), pT3 or pT4 patients (p<0.004) without analogous relation in moderately differentiated (G2) tumors, node negative patients or pT1 or pT2 patients. P53 and IGF-I negatively correlated in all CRC patients (p<0.04) and VEGF{H} individuals of pT3 or pT4 (p<0.05) without any significant linkage in tumors of pT1 or pT2. The positive correlation between serum P53 and VEGF points at mutation of P53 and is a highly probable sign of poor prognosis in colorectal cancer. For now it can not be excluded that the binary analysis of serum P53 and VEGF could help select CRC patients endangered by rapid growth and lymph node metastases.

To give or not to give recombinant EPO to anemia endangered cancer patients.

EPO is known as an inducer of maturation and proliferation of erythrocytes. Moreover, it favours angiogenesis. In several studies it was encountered that EPO is a trophic agent that mediates survival and inhibits apoptosis of hypoxia affected cells, particularly those which build masses of irregularly vascularized cancers. The main task concerning EPO for oncologists is the choice to give or not to give recombinant EPO to anemia endangered cancer patients. EPO can do the quality of life better and cause recovery from anemia post chemotherapy and radiation of cancer patients. Nevertheless, EPO therapy shortens survival of patients in some cancers, in which antiapoptotic effect of EPO predominates directly in malignant cells. Thus, separately in every type of cancer, therapeutic use of recombinant EPO calls for prior investigations, if EPO signaling causes proliferation of cancer cells by direct stimulation of EPOR positive malignant cells. Unless the proliferative effect of EPO on cancer cells is excluded, its use in the therapy of anemia in cancer patients is not quite safe.

Expression of the Insulin Receptor Substrate 1 in primary tumors and lymph node metastases in breast cancer: correlations with Bcl-xL and Bax proteins.

In our previous investigation Insulin Receptor Substrate 1 (IRS-1) correlated with proliferation marker Ki-67 in human breast cancer. The aim of the present study was to assess relationships between IRS-1 expression and anti-apoptotic Bcl-xL as well as proapoptotic Bax proteins, assessed by immunohistochemistry, in primary tumors and lymph node metastases of breast cancer. IRS-1 is positively associated with both Bcl-xL and Bax in primary and metastatic tumors. Thus, our results could suggest that IRS-1 might affect turnover of cancer cells and breast cancer progression through activation of mitogenesis and participation in the regulation of the balance between anti- and proapoptotic pathways.

Characterization of cytoplasmic arginine-rich basic protein of Guerin epithelioma.

Arginine-rich basic protein from cytoplasma of Guerin epitheliomas has been isolated and characterized. It contains five amino acids: arginine, lysine, glycine, alanine and glutamic acid which make together 74% of all amino acid residues. The protein has a cationic character with an isoelectric point of 8.2. No carbohydrate component was found in this protein. The significance of arginine-rich basic protein in the cytoplasma of Guerin epithelioma is discussed briefly.

The comparison of aminotransferase activities in normal and Guerin epithelioma bearing rats.

The activities of 13 aminotransferawes in Guerin epithelioma and in the liver of normal and tumor bearing rats were investigated. Alanine and aspartate aminotransferases show the highest activity in all investigated tissues. In the liver of normal rats high arginine, tyrosine and phenylalanine aminotransferase activities were found. In tumor tissue high level of branched chain amino acid (leucine, valine and isoleucine) aminotransferases were observed. Increase in aminotransferase activities in the liver of tumor bearing rats was found. In order to elucidate the mechanism of this increase an inductive effect of hydrocortisone and protein free extract of tumor tissue on liver aminotransferases has been investigated. The tumor extract did not exert an inductive action. An inductive effect of hydrocortisone was not identical with the change in aminotransferase activities observed in the liver of tumor bearing rats.