Relation between human papillomavirus positivity and p16 expression in head and neck carcinomas--a tissue microarray study.

Overexpression of p16 has been demonstrated to be strongly related to the presence of HPV16, 18. Squamous cell carcinoma of the head and neck has been shown to be associated with human papillomavirus (HPV) infection. The main aim of this study was to investigate the relationship between HPV presence and p16 expression in a representative collection of 60 head and neck carcinomas by tissue microarrays.

Alterations of the retinoblastoma and p16 pathway correlate with promoter methylation in malignant fibrous histiocytomas.

Recent reports indicate that the alterations in the p16 and pRb pathways can influence tumour progression and poor prognosis in several tumours. The objective of this study was to analyse p16 and pRb expression in161 patients with malignant fibrous histiocytomas (MFH). By immunohistochemistry, p16 and pRb were demonstrated in 25% and 56% of MFH, respectively.

Analysis of DNA mismatch repair gene expression and mutations in thyroid tumours.

Alterations of DNA mismatch repair genes, primarily demonstrated in hereditary nonpolyposis colorectal carcinomas, were reported to be of relevance for the progression of several sporadic tumours. In this study, the expression and mutations of MLH1, MSH2, PMS1 and PMS2 in a panel of thyroid tumours, including nodular hyperplasia, follicular adenomas and carcinomas, were investigated. The expressions of MLH1, MSH2 and PMS1 were generally higher in malignant tumours than in benign lesions (p < 0.

Altered expression of DNA double-strand repair genes Ku70 and Ku80 in carcinomas of the oral cavity.

The relevance of double-strand DNA repair genes has been demonstrated in several tumours. The main aim of this study was to analyse the expression of the heterodimers Ku70 and Ku80, building regulatory subunits of the DNA-dependent protein kinase in 40 oral carcinomas. Ku70 expression was found in 87.

Exonic deletions of mismatch repair genes MLH1 and MSH2 correlate with prognosis and protein expression levels in malignant melanomas.

The mutations of MLH1 and MSH2 have been reported to be responsible for malignant transformation and tumour progression in several sporadic tumours. Eighty-six primary malignant melanomas with known follow-up were investigated. Point mutations of DNA mismatch repair MLH1 and MSH2 in malignant melanomas were not found.

Loss of Ku70/Ku80 expression occurs more frequently in hereditary than in sporadic colorectal tumors. Tissue microarray study.

Ku70 and Ku80 proteins take part in the repairing of DNA double-strand breaks by their function as a regulatory subunit of the DNA-dependent protein kinase. In this study, expression of both genes was analyzed in colorectal carcinoma tissue arrays applying immunohistochemistry. Expression of both genes decreased along with pT stage.

Proposal of a new grading system for malignant fibrous histiocytomas.

The proposed grading system for malignant fibrous histiocytomas (MFH) comprises 3 grades of malignancy. Analogous to other grading systems, the system includes the factors of mitotic rate and necrosis. In addition to these two factors, the concept of cellularity was included.

Relationship of nm23 expression to proliferation and prognosis in malignant melanomas of the oral cavity.

Twenty-nine cases of oral melanomas were investigated for nm23 and Ki67 antigen expression, as well as for the fraction of tumour cells in S-phase, using immunohistochemical techniques and DNA cytophotometry. Nm23 expression was significantly reduced and Ki67 antigen expression increased in primary tumours with either lymph node or organ metastases in comparison to tumours without metastases. The percentages of Ki67 immunoreactive tumour cells and cells in S-phase correlated positively with each other and negatively with the percentage of nm23-expressing cells.

Cytokeratin expression correlates with aneuploidy in cytological specimens of melanoma metastases.

It has been postulated that the high malignancy of melanomas could be connected with an increased cytokeratin (CK) expression. In order to define the relationship between CK expression and genetic instability of melanoma metastases, ploidy-related parameters were compared in cytological specimens of CK-positive and CK-negative melanoma metastases. CK expression was investigated immunohistochemically in 35 melanoma liver metastases and in 52 melanoma lymphatic metastases.

Application of new ploidy-related parameters for the diagnosis of ovarian tumours.

Differential diagnostics of borderline ovarian tumours and ovarian carcinomas is generally based on morphological criteria, which are not always sufficient for final diagnosis. Therefore, we investigated the practical diagnostic application of the CAS200 image analyzer and new ploidy-related parameters in a series of 68 borderline tumours and 42 low-grade carcinomas of the ovary. Highly significant differences between borderline and malignant lesions were found for the percentage of diploid cells (p = 0.

Analysis of central regulatory pathways in p53-deficient primary cultures of malignant fibrous histiocytoma exposed to ifosfamide.

Soft tissue sarcomas frequently carry p53 mutations reducing chemotherapeutical response. Especially malignant fibrous histiocytoma (MFH) reveals a reduced ifosfamide (IF) chemosensitivity when compared to other sarcoma entities. This is the first study to analyze MFH cells for the effects of IF on the expression of the pathways P16-CDK4-Rb and P14ARF-MDM2-P73 regulating cell cycle.

Application of in situ hybridization probes for MLH-1 and MSH-2 in tissue microarrays of paraffin-embedded malignant melanomas: correlation with immunohistochemistry and tumor stage.

Defects in DNA mismatch-repair genes MLH1 and MSH2 reported primarily in hereditary nonpolyposis colorectal carcinoma are present in many sporadic tumors, including malignant melanomas. The main aim of this study was to investigate the expression of these genes in malignant melanomas in relation to tumor stage. An experiment was performed on paraffin-embedded tissue microarrays of malignant melanomas applying in situ hybridization with probes produced by our research group and immunohistochemical techniques.

Down-regulation of Ku 70 and Ku 80 mRNA expression in transitional cell carcinomas of the urinary bladder related to tumor progression.

DNA-dependent protein kinase (DNA-PK) containing the regulatory subunits Ku 70 and Ku 80 plays a prominent role in the repair of double-stranded DNA breaks by a nonhomologous end-joining pathway maintaining genomic stability. In an attempt to elucidate the significance of the DNA-PK complex for human urothelial carcinogenesis, the expression of Ku 70 and Ku 80 was studied in 71 transitional cell carcinomas (TCC) of the urinary bladder of various grades and stages, and in relation to lifestyle and occupational bladder cancer risk factors. To analyse the mRNA expression of Ku 70 and Ku 80, real-time quantitative reverse transcription-polymerase chain reaction was used and the protein expression assessed by immunohistochemistry.

Alteration of the vascular endothelial growth factor and angiopoietins-1 and -2 pathways in transitional cell carcinomas of the urinary bladder associated with tumor progression.

Neoangiogenesis is assumed to play an important role in the progression, metastasis and prognosis of a wide variety of tumors. To get insights into the molecular-genetic pathways and the biological role of angiogenesis in urothelial carcinogenesis, we analyzed comparatively the expression of the mRNA of the vascular endothelial growth factor (VEGF) and of the angiopoietins-1 and -2 (Ang-1 and Ang-2) in 71 transitional cell carcinomas (TCC) of the urinary bladder in relation to the tumor grades and stages, and referring to epidemiological risk factors. Using real-time quantitative reverse transcription-polymerase chain reaction, low-stage superficial TCC expressed VEGF and Ang-2 mRNA at a significantly higher level than high-stage muscle invasive carcinomas, and low-grade TCC at an insignificantly higher level than high-grade tumors.

Cytokeratin positivity in paraffin-embedded malignant melanomas: comparative study of KL1, A4 and Lu5 antibodies.

The unclear role of cytokeratin (CK) in the progression and diagnostics of malignant melanomas stimulated us to compare the reactivity of three antibodies directed to CK in 109 paraffin-embedded melanomas. By far the majority of melanomas did not express cytokeratin even at the<1% level, only vimentin. In about 6% of melanomas it was possible to find CK expression ranging between 3 and 40% of melanoma cells.

Alteration of the MDM2-p73-P14ARF pathway related to tumour progression during urinary bladder carcinogenesis.

Transitional cell carcinomas (TCC) of the urinary bladder develop by a multistep process characterized by various stages of transformation differing in their grade of malignancy and biological behaviour. Since the prospective clinical outcome cannot be reliably predicted on histopathological grounds, we analysed the mRNA expression of the MDM2-p73-P14ARF tumour surveillance pathway in an attempt to detect alterations of gene activity, allowing a better understanding of the mechanisms responsible for conversion of low to high malignant TCC. Expression of the mRNA was determined in 71 TCC of various grades and stages using the real-time quantitative reverse transcription-polymerase chain reaction.

Analysis of the p53-hMDM2-p21 (WAF1/CIP1) Cell Cycle Regulation Pathway in Malignant Fibrous Histiocytomas.

This study was undertaken to analyze patterns of expression of critical cell cycle regulators (CCR) involved in the p53 pathway in malignant fibrous histiocytomas (MFH). Protein expression was assessed using immunohistochemistry analyzing p53, hMDM2 and p21 (WAF1/CIP1) phenotypes. p53- and hMDM2-positive phenotypes were found to be associated with low p21 levels (p<0.

Comparison of DNA ploidy status and DNA ploidy-related parameters in malignant melanoma tissue microarrays and full sections.

A new high-throughput tissue-arraying technique, now frequently used in tumor pathology, requires standardization of methods of DNA analysis, previously applied in full histological sections. The main objectives of this study were to evaluate DNA ploidy status and DNA ploidy-related parameters using the CAS200 image analyzer in malignant melanoma tissue microarrays and to compare them with full histological sections. Comparison of DNA ploidy-related parameters, including percentage of diploid cells, percentage of aneuploid cells between 2c and 4c, percentage of tetraploid cells, percentage of aneuploid cells between 4c and 8c, percentage of octaploid cells, percentage of 16-ploid cells, and 5c exceeding rate, did not reveal any significant differences between malignant melanoma tissue microarrays and full sections.

Analysis of adenomatous polyposis coli gene expression, APC locus-microsatellite instability and APC promoter methylation in the progression of melanocytic tumours.

Adenomatous polyposis coli gene (APC) defects have been demonstrated for the first time in familial adenomatous polyposis. Recent reports indicate that the APC gene is an intermediary between cell adhesion molecules and the cytoskeleton and that it may function as a gatekeeper of colonic epithelial proliferation. The objective of this study was to analyse APC's presence in lentigos, primary melanomas and melanoma metastases.

Stem cell based therapeutical approach of male infertility by teratocarcinoma derived germ cells.

Infertility affects 13-18% of couples and growing evidence from clinical and epidemiological studies suggests an increasing incidence of male reproductive problems. There is a male factor involved in up to half of all infertile couples. The pathogenesis of male infertility can be reflected by defective spermatogenesis due to failure in germ cell proliferation and differentiation.

Altered mRNA expression of the Rb and p16 tumor suppressor genes and of CDK4 in transitional cell carcinomas of the urinary bladder associated with tumor progression.

Based on the concept that tumor suppressor genes are involved in the pathogenesis of urinary bladder carcinogenesis, we analysed the mRNA expression of the retinoblastoma (Rb) and p16 (CDKN2, INK4A, MTS1) genes as well as of the proto-oncogene cyclin D-dependent kinase 4 (CDK4) in 71 transitional cell carcinomas (TCC) of the urinary bladder in relation to the tumor grades and stages, and with reference to certain lifestyle and occupational risk factors. Using real-time quantitative reverse transcription-polymerase chain reaction, high-stage muscle invasive TCC expressed the Rb, p16 and CDK4 mRNA at lower levels than low-stage superficial cancers, indicating down-regulation to be linked with tumor progression. The drop of the expression in the group of grade 2 TCC when invading the muscle layer compared to grade 2 carcinomas with a superficial pattern of growth is considered to represent a key event in promoting urothelial carcinogenesis in this subset of carcinomas.

Altered expression and new mutations in DNA mismatch repair genes MLH1 and MSH2 in melanoma brain metastases.

Brain metastases, including those of malignant melanoma (known for its high genomic instability), are the most common intracranial tumors. The main objective of this study was to investigate expression and mutation in the DNA mismatch repair system in melanoma brain metastases. Expression of MLH1, MSH2, PMS1 and PMS2 was investigated immunohistochemically in 31 melanoma metastatic tumors.

Quantitative Analysis of Ku70 and Ku80 mRNA Gene Expression in Melanoma Brain Metastases. Correlation with Immunohistochemistry and Hybridization.

Background: Altered expression and prognostic significance of DNA double-strand repair genes Ku70 and Ku80 has been shown by our research group for malignant melanomas. High genomic instability known for melanoma brain metastases stimulated us to analyze Ku70 and Ku80 expression in melanoma brain metastases.

Materials And Methods: Quantitative evaluation of mRNA Ku70 and Ku80 expression was performed in 13 melanoma brain metastases.

Application of new in situ hybridization probes for Ku70 and Ku80 in tissue microarrays of paraffin-embedded malignant melanomas: correlation with immunohistochemical analysis.

Ku70 and Ku80 proteins are responsible for the repair of DNA double-strand breaks and function as a regulatory subunit of the DNA-dependent protein kinase. In this study we analyzed expression of both genes in malignant melanoma tissue arrays applying in situ hybridization probes produced by our research group and using immunohistochemical analysis. Expression of both genes was down-regulated as melanoma progressed.