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)

Analysis of the DNA content in the progression of recurrent and metastatic melanomas

Ploidy status and ploidy minted parameters of 18 primary melanomas, 32 recurrences and 18 lymphatic metastases were investigated applying CAS200 image analyzer All the tumours investigated were either suspicious for aneuploidy (Auer III) or clearly aneuploid (Auer IV). Primary melanomas differed from recurrent tumours concerning the percentage of aneuploid cells between 4c and 8c and 5c ER. Comparison of cutaneous tumors with lymphatic metastases showed a significant difference concerning the percentage of aneuploid cells between 2c and 4c. An already high aneuploidy rate in primary rumours suggests that recurrent and metastatic clones of cells are present in early stages and that aneuploidy status in primary melanomas could be regarded as one of the risk factors of recurrences and metastases

Differential binding activities of lectins and neoglycoproteins in human testicular tumors

Testicular germ-cell tumors, a morphologically and clinically diverse group of malignancies provide an ideal model for investigating the biology of glycoconjugates because the biosynthesis of oligosaccharide chains of glycoproteins monitored by plant/invertebrate lectins often changes during tumorigenesis, tumor progression, and metastasis. To investigate such changes in germ-cell tumors, we analyzed 67 surgical specimens from 31 seminomas, 32 embryonic carcinomas, and four choriocarcinomas using glyco- and immunohistochemistry that involved five plant/invertebrate lectins, 16 neoglycoproteins, and galectin-1 antibody. The results showed that some of these markers, such as melibiose-, lactose-, and beta-N-acetylgalactosamine-BSA-biotin were clearly differentially expressed amongst these tumors and between primary and metastatic embryonic carcinomas. The differences in staining for positivity, intensity, and heterogeneity indicate that the differential display of glycoconjugates in tumor cells may be important in tumor growth, metastasis, or prognosis because subtypes of these tumors behave quite differently from one another. Furthermore, we also found identical staining for positivity between most neoglycoproteins and their corresponding lectins, though the staining intensity of neoglycoproteins was weaker. This suggests that neoglycoproteins may be useful markers to replace their plant lectins

Ultrasound imaging of Nd : YAG laser-induced tissue coagulation in porcine livers

Alms: Absorption of laser light energy induces denaturation of proteins and thermocoagulation of irradiated tissue. Recently, MRI-guided laser coagulation in combination with MR thermometry was reported as a treatment of liver tumours. In the present study ultrasonographic imaging was evaluated for its suitability in laser induced tissue thermocoagulation. Methods: Fresh porcine livers were used for ex vivo examinations. Placement of the laser catheter and tissue coagulation during laser light emission were online monitored by ultrasonography. Nd:YAG laser-induced tissue damage was evaluated by macroscopical and microscopical examinations of histological sections. Results: During laser light emission a marked hyperdense signal enhancement was observed by ultrasonography which strongly correlated with the extent of macroscopic tissue damage. The size of laser-induced coagulation zone depended on both the power setting and total energy delivered. Carbonization of the tissue surrounding the laser tip is a limiting factor because of laser light absorption. However our data indicate that using appropriate laser energy and exposure time prevent carbonization although carbonization can not be visualized by ultrasonography. Conclusions: It is concluded from the present ex vivo studies that laser coagulation can be effectively performed under ultrasonographic guidance

Analysis of the DNA mismatch repair proteins expression in malignant melanomas

The importance of properly functioning DNA mismatch repair has been shown in several tumour types both hereditary and sporadic but not yet in malignant melanomas. The aim of this study was to examine the expression of DNA mismatch repair genes (MLH1, MSH2, PMS1 and PMS2) in primary melanomas and to define their possible prognostic impact in 106 primary melanomas. MLH1 was found in 64 and MSH2 in 61 out of 106 melanomas. PMS1 and PMS2 proteins were present in 69 and 67 tumours, respectively. Loss of the expression of DNA mismatch repair proteins correlated with the increase of Clark levels. Cox regression analysis demonstrated some prognostic significance for PMS1 (forward p = 0.0018 and backward selections p=0.0277), MLH1 (only forward selection p =0.0081) and MSH2 (only backward selection p =0.0115)

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