Prognostic importance of selected molecular immunohistochemical markers and DNA ploidy in endometrial cancer.

UNLABELLED: The aim of the study was the analysis of the new molecular genetic immunomarkers (p53, c-erbB-2, Ki 67, bcl-2) hormonal receptors (ER, PR) and ploidy disturbances and their relation to the most important prognostic factors for endometrial cancer. The study group consisted of 135 endometrial cancer patients. Biopsies of the tumours obtained at operations were routinely histopathologically examined. Subsequenly, the immunohistochemical tumour markers were determined. The same biopsies were examined by microdissection and flow cytometric ploidy analysis and karyotyping. The findings were compared with the most important prognostic factors for endometrial cancer, mainly with clinical stage of the disease and grade. RESULTS: High expression of p53, Ki 67, c-erbB-2 and low rate of progesterone receptors was found in the prognostically unfavourable group (G 3). Aneuploidy was found in 72% in the group of poorly differentiated endometrial cancers (G 3) in contrast to 27% in the group of G1 and G2 tumours, but this difference was not statistically significant. CONCLUSIONS: Identification of p53, Ki 67, c-erbB-2, PR and determination of DNA ploidy is a useful tool to specify a group of prognostically unfavourable patients.

[Paraneoplastic neurological syndrome in 64-year-old patient in association with a small cell lung carcinoma]. / Paraneoplastický neurologický syndrom u 64letého pacienta s malobunecným karcinomem plic - kazuistika.

BACKGROUND: Paraneoplastic neurological syndromes are rare conditions manifest as psychiatric/neurological symptoms. They are caused by autoimmunne cross-reaction leading to destruction of the central nervous system. CASE: We present the case of a 64-year-old patient hospitalized for 6 months at the Department of Psychiatry for persisting depression. During that time he progressed to delirium. A diagnosis of diffuse encephalopathy was made, but further examination revealed a small cell lung cancer with generalisation. A paraneoplastic syndrome was finally diagnosed after autoptic and histologic examination. CONCLUSION: Paraneoplastic neurological syndromes can be early signs of malignancy and may considerably precede oncologic diagnosis.

[Prognostic importance of selected molecular genetic immunohistochemical markers and DNA ploidy in endometrial cancer]. / Prognostický význam vybraných molekulárne-genetických imunohistochemických markeru a DNA ploidity u karcinomu endometria.

OBJECTIVE: The aim of the study was the analysis of the new molecular genetic immunomarkers (p53, c-erbB-2, Ki 67, bcl-2) hormonal receptors (ER, PR) and ploidy disturbances and their relation to the most important prognostic factors for endometrial cancer. DESIGN: Prospective study. SETTING: Dept. of Gynaecology and Obsterics, Laboratory of Experimental Medicine, Institute of Pathology, Institute of Molecular and Transplational Medicine, Medical Faculty and University Hospital, Olomouc. METHODS: The study group consisted of 88 endometrial cancer patients. The biopsies of the tumours obtained at operations were routinely histopathologically examined. Subsequently, the immunohistochemical tumormarkers were determined. The same biopsies were examined by microdissection and flow cytometric ploidy analysis and karyotyping. The findings were compared with the most important prognostic factors for endometrial cancer, mainly with clinical stage of the disease, grade and histopathological type. RESULTS: Aneuploidy was found in 71% in the group of poorly differentiated endometrial cancers (G3) in contrast to 47% in the group of G1 and G2 tumours. High expression of p53, Ki 67, c-erbB-2 and low rate of sex hormone receptors was found in the prognostically unfavourable group (G3). CONCLUSIONS: Aneuploidy seems to be an important prognostical factor for endometrial cancer patients. Identification of p53, Ki 67, c-erbB-2, ER a PR is a useful tool to specify a group of prognostically unfavourable patients.

[Fibroblasts--known or unknown cells]. / Fibroblasty--bunky známé ci neznámé?

Fibroblasts form the main component of the cell tissue microenvironment, and their basic function is to maintain cell integrity and tissue homeostasis. Fibroblasts essentially participate in wound repair. Recently, increased interest has been focused on the role of fibroblasts in cancers, where they are involved in the ransformation of a tumour stroma, and via production of numbers of cytokines and growth factors participate in tumour progression. With regard to their impact in cancerogenesis, fibroblasts become a new target of cancer therapy.

The role of vascular endothelial growth factors and their receptors in malignant melanomas.

Vascular endothelial growth factors (VEGFs) have a leading role among variety of angiogenic factors. Together with their receptors, they play an important role in endothelial cell proliferation and/or elongation, migration and vascular morphogenesis. In order to determine their possible role in malignant melanoma progression, VEGF (representing VEGFA), VEGF-C and VEGFR-1, -2, -3 immunohistochemical expression on formalin-fixed, paraffin-embedded tissue sections were evaluated. A total of 196 tissue samples consisting of 130 malignant melanomas (MM) with various vertical depth of invasion, 15 metastatic melanomas, and 66 nevi including dysplastic nevi and melanocytic nevi were analysed. Production of both VEGFs were common in benign melanocytic tumors while MM exhibited significant upregulation of VEGF (p<0.0027) and VEGF-C (p<0.0001). The proteins were also detected within stromal cells surrounding tumors, particularly in fibrocytes/ fibroblasts, macrophages and endothelial cells. They also exhibited significant increase in malignant lesions (p<0.0001). VEGFRs were localized in tumor, as well in stromal cells. Although expression of VEGF receptors was significantly higher in MM versus nevi (p<0.002 for VEGFR-1, p<0.004 for VEGFR-2 and p<0.0001 for VEGFR-3), a considerable percentage of MM were negative. There were no correlations between sentinel node positivity and all investigated proteins. When clinical outcome was evaluated, progression of the disease positively correlated with VEGF (p<0,007) and VEGF-C (p<0,008) expression VEGF (p<0.001) and VEGF-C (p<0.0001) positively correlated with nestin expression in the capillary endothelium, which was used for angiogenesis detection. Our work demonstrated that upregulation of VEGFs is associated with progression of malignant melanomas. The protein expression in the tumor microenvironment highlights their importance in malignant stromal phenotype which may serve as a potential target for the anticancer therapy.

[The role of intermedial filament nestin in malignant melanoma progression]. / Význam intermediárního filamenta nestinu v progresi maligního melanomu.

UNLABELLED: Nestin is one of intermedial filaments exprimed in proliferating progenitor cells of the CNS and PNS (central and peripheral nervous system). Postnatal reexpression of the protein occures mainly in CNS tumors and correlates with a high grade of malignancy. The aim of our study is assessment of the nestin expression in benign and malignant skin melanocytic lesions with respect to presume a prognostic role of this protein. We examined 127 bioptic specimens, including 42 nodular melanomas (NM), 32 superficial spreading melanomas (SSM), 10 dysplastic nevi and 43 common intradermal or dermoepidermal nevi. We proved significant increase in nestin expression in melanoma groups, especially in nodular melanomas, where nestin was localized mainly in the peripheral, invasive areas of the tumor mass. CONCLUSION: Detection of nestin expression might be used as an additional melanocytic tumour marker.

Proto-oncogene c-myc in uterine cervix carcinogenesis.

The biological behaviour of precancerous and early stages of uterine cervix carcinoma is not always easily predictable. It is important therefore to identify new biological markers which could more reliably predict the evolution of the disease or provide important therapeutic targets. To establish the role of the proto-oncogene c-myc in uterine cervix tumorigenesis, we examined 96 tissue samples of different degrees of cervical intraepithelial neoplasia (CIN1-CIN 3), in situ (CIS) or invasive squamous cell carcinoma (ISCC) and control cases. Indirect immunohistochemical techniques were used to detect the c-myc expression. Significantly higher levels of Myc protein were found in keratinocytes of high-grade dysplasias in comparison to low-grade dysplasias and control cases. There was no difference between low-grade CIN and a control group of patients. The same significant changes between above mentioned groups were seen in surrounding stromal cells (fibrocytes, fibroblasts, some endothelial cells and lymphocytes). We confirm that expression of c-Myc protein is increased not only in uterine cervix cancer but also in the premalignant lesions. Problem for discussion seems there for whether increased Myc expression in stromal cells might create a more tumor promoting microenvironment which may support the growth and proliferation of transformed cells.

DNA ploidy correlates with grade, proliferation and clinical outcome but not with presence of human oncogenic HPVs or expression of Bcl-2 in preneoplastic and neoplastic lesions of the uterine cervix.

The aim of this study was to analyse whether DNA ploidy correlates with proliferative activity as measured by PCNA expression, presence of oncogenic human papillomaviruses (HPVs), histological grade, expression of antiapoptotic protein Bcl-2 and clinical outcome in a cohort of 57 preneoplastic and neoplastic lesions of the uterine cervix. The samples were analysed using computer image cytomorphometry of Feulgen stained sections, standard indirect immunohistochemistry and hybridisation of HPV DNA in situ. The ploidy data were found to be significantly different between low/high grade preneoplasia and invasive carcinoma. Significant positive relationships were also found between DNA content and proliferation of lesions, and DNA content and clinical behavior of the lesions. Nevertheless, no relationship between DNA ploidy and HPV/Bcl-2 status was established.

Expression of Bcl-2 in dysplastic and neoplastic cervical lesions in relation to cell proliferation and HPV infection.

Expression of the bcl-2 gene has been shown to effectively confer resistance to programmed cell death in a variety of tumors. The bcl-2 proto-oncogene is involved in the development of human follicular lymphomas and also in a number of solid tumors such as carcinomas of prostate, breast, lung and GIT. The present study was designed to analyze the role of Bcl-2 expression in cervical intraepithelial squamous neoplasias (CIN) and cervical invasive carcinomas. Special attention was given to the association of Bcl-2 expression with the grade of the lesion, proliferative activity (expression of nuclear antigen of proliferative cells - PCNA) and human papillomavirus (HPV) DNA positivity. We examined tissue samples obtained from 86 women with varying degrees of cervical disease. Bcl-2 and PCNA were investigated using immunohistochemical staining and detection of HPV DNA was performed by hybridization in situ. Increased Bcl-2 expression was observed in advanced degrees of dysplasia and in carcinomas. We found a strong association between the presence of Bcl-2 in pathological epithelium with both the degree of dysplasia and the proliferative activity. We also observed a significant correlation between the amount of Bcl-2 positive lymphocytes infiltrating the lesions and the degree of disease. We, therefore, suggest that Bcl-2 expression in these lymphocytes may influence the antiviral or antitumor immune response. On the other hand we did not detect any significant correlation between the Bcl-2 oncoprotein and the presence of HPV. These results indicate that Bcl-2 may play an important role in the development of cervical cancer.

[Inflammatory stromal reaction in epithelial neoplasia of the uterine cervix in correlation with HPV infection]. / Zánetlivá stromální reakce v epiteliálních neoplaziích delozního hrdla v korelaci s infekcí HPV.

260 cases of women with epithelial neoplasias of the uterine cervix were studied: HPV infection was detected by DNA in situ hybridization and serology, simultaneously structure and intensity of stromal inflammatory reaction (SR) were evaluated (semiquantitatively) as well as standard clinical immunological parametres investigated by serology. Results proved the same character of SR in intraepithelial lesions and invasive carcinomas and the intensity of SR increasing in relation to the gravity of epithelial dysplasia. There was not found any significant difference in SR between cases with detected HPV infection and cases lacking it. Summarized immunological parametres were in limits of normal reference range.