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<0.01). This observation can find potential diagnostic application in the differentiation of follicular adenomas from follicullar carcinomas of the thyroid. No point mutations in the DNA mismatch repair genes MSH2 (exon 12, 13) and MLH1 (exon 15, 16) were found

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. There was a correlation between CK expression and pTstage. Cytokeratin-expressing tumours were found in the more advanced pT-stages. The independent prognostic values of none of the three CK antibodies investigated could be shown

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. The prognostic relevance of the grading systems published by Costa, Coindre, van Unnik, Pezzi and Tsujimoto as well as the grading system proposed by the present study was tested on 161 MFH. The results showed that all grading systems tested produced clearly significant differences (p<0.01) with regard to the survival estimated for patients with various grades of malignancy. These results revealed the superiority of systems that use 3 grades of malignancy over a 2-grade classification. The proposed grading system yielded a lower percentage of grade II tumours (37%) than the grading systems of Coindre (60%) and van Unnik (70%). In the multivariate analysis of all grading systems, the proposed grading system was the only one to show prognostic relevance (p<0.05)

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. Exon 12 (MSH2) was not present in 26 out of the 86 melanomas and exon 13 (MSH2) was lost in 25 of the tumours. The loss of exon 15 (MLH1) was observed in 22 out of the 86 tumours and the loss of exon 16 (MLH1) in 24 melanomas. The loss of exons correlated strongly with the loss of MLH1 and MSH2 protein expression. In multivariate analysis, including all 4 exons and expressions of MLH1 and MSH2, prognostic significance was found only for loss of exon 12 (MSH2) and loss of exon 15 (MLH1)

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. The presence of HPV (HPV6,11-low risk, HPV16,18-high risk) was detected by applying in situ hybridisation. P-16 protein expression was detected imuunohistochemically. HPV6,11 positivity was observed in 10 out of 60 carcinomas. HPV16,18 presence was found in 30 out of 60 tumours. P-16 expression was detected in 35 out of 60 tumours. A statistically significant relationship was demonstrated between HPV16,18 presence and increased expression of p16. Also the HPV6, 11 presence was significantly correlated with p16 immunoreactivity. Additionally, this study demonstrates that it is possible to analyse p16 expression and HPV presence 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. Cox regression analysis demonstrated an independent prognostic influence of both genes. Generally, the loss of p16 and pRb expression correlated with poorer prognosis. Promoter methylation of p16 was found in 16/42 of p16 negative MFH and of pRb in 2/42 of pRb-negative MFH. It can be concluded that p16 and pRb alterations play an important role in the progression of soft tissue sarcomas