Altered Splicing of JARID1B in Development of Human Cutaneous Melanoma?

Upregulated expression of histone H3K4 demethylase JARID1B has been found in several types of human cancer, but the expression pattern of this protein in benign naevi and human cutaneous melanomas seems to differ from that described for other tumors. We demonstrate that the apparent contradiction may be because of the fact that the malignant transformation of melanocytes is associated not so much with a general enhancement of a total expression of JARID1B but rather with a change in relative expression levels of individual splicing variants of the protein. Our data indicate that parallel immunohistochemical assays of the expression levels of all the isoforms and of the RBP2-H1 variant of JARID1B may be an efficient technique of differentiating between benign naevi and melanomas.

Case presentation - A five-year survival of the patient with glioblastoma brain tumor.

This paper presents an atypical case of a patient with brain tumor of the glioblastoma multiforme (GBM) type who achieved a 5-year survival. Some general information is provided including epidemiology, diagnostic and treatment procedures (surgery and radio-chemo-therapy), and prognosis of survival related to GBM. The course of the disease, including its main symptoms, individual reasons for the delay of adjuvant treatment, after the primary surgical treatment, 37-month period of the decease free survival, as well as comprehensive management after the tumor recurrence are also presented. Histopathology confirming the clinical diagnosis is discussed in a separate chapter.

The presence and clinical implications of α-2,6-galactose-linked sialic acids in non-small-cell lung cancer brain metastases--preliminary study.

Brain metastases (BM) in non-small-cell lung cancer (NSCLC) patients present an increasing clinical challenge. Identifying biomarkers which specifically identify patients at high risk of BM may improve their early diagnosis, which is crucial for surgical and radiotherapeutic treatment outcome. Alpha-2,6-sialyltransferase (α-2,6-ST) and the primary product of its activity, alpha-2,6-galactose-linked sialic acids (α-2,6-GalSA) have been found responsible for the adhesion of tumor cells to the brain vessels' endothelium and enabling their transmigration through the blood-brain barrier in brain metastatic tumors. The aim of the study was to investigate by histochemical method the presence and possible role of α-2,6-GalSA in the formation of brain metastasis in NSCLC. In the screening phase 76 metastatic brain tumors were stained for α-2,6-GalSA and the second phase involved an identical staining of 20 primary tumors of patients who had their primary tumors treated with surgery or definite radiochemotherapy yet who later developed BM. The results were compared to a control group of 22 patients treated with surgery for NSCLC and who survived 5 years without the recurrence of disease. Alpha-2,6-GalSA presence was found to be down-regulated in poorly differentiated tumor types, whereas majority of differentiated tumors overexpressed it. This was statistically significant for both BM and the primary tumors. The expression of α-2,6-GalSA remained stable in primary and metastatic tumor pairs, however, no statistically significant differences were observed between study and control groups. Within the study group, a higher α-2,6-GalSA expression was associated with better overall survival, but not all statistical models found this result significant. Further studies are recommended to validate these findings.

JARID1B expression in human melanoma and benign melanocytic skin lesions.

It has been suggested that dynamically regulated expression of the JARID1B protein is required for the continuous growth of tumors and at the same time downregulated in melanoma. The majority of the data on a role of JARID1B in maintaining tumor growth has come from in-vitro and xenografting experiments, with only one immunohistochemical study involving human tissues. We compared JARID1B expression levels in human melanomas and benign nevi and analyzed patterns of spatial distributions of positive cells among different skin layers of the lesions. The expression of JARID1B was evaluated by immunohistochemistry in formalin-fixed paraffin-embedded samples of 30 nevi, 27 primary melanomas, four lymph node metastases, and one local recurrence of melanoma. Staining for JARID1B protein was stronger in melanomas compared with nevi. We also found a significant difference in the spatial distribution of positive cells in individual skin layers of nevi and melanomas. Staining of melanocytes located in granular and spinous layers of nevi was observed very rarely, whereas for melanomas, the mean percentage fractions of positive cells present in these layers exceeded the maximum values found for nevi. The spatial patterns and expression levels of JARID1B did not change significantly with melanoma progression and were similar for primary, metastatic, and recurrent melanomas. Contrary to earlier reports, this study shows enhanced expression of JARID1B by melanoma cells and indicates that such an enhancement may be an early event in the disease progression, is not correlated with melanoma invasiveness, and therefore may not be a suitable candidate as a prognostic marker.

The value of cyclooxygenase-2 expression in differentiating between early melanomas and histopathologically difficult types of benign human skin lesions.

Early cutaneous melanomas may present a substantial diagnostic challenge. We have already reported that expression of cyclooxygenase-2 (COX-2) may be useful for differentiating between cutaneous melanomas and naevi. The purpose of this study was to examine the value of COX-2 in a challenging task of differential diagnosis of early melanomas and melanocytic naevi considered by histopathologists as morphologically difficult to unequivocally diagnose as benign lesions. The material for the study comprised formalin-fixed paraffin-embedded samples of 46 naevi (including 27 cases of dysplastic, Spitz and Reed naevi) and 30 early human cutaneous melanomas. The expression of COX-2 was detected immunohistochemically. Melanomas expressed COX-2 significantly more strongly compared with naevi. The test, on the basis of determination of the percentage fractions of COX-2-positive cells, allows for differentiation of early skin melanomas and naevi with high sensitivity and specificity. Receiver operating characteristic analysis of the test results yielded areas under receiver operating characteristics curves (AUC)=0.946±0.030 for central regions and AUC=0.941±0.031 for the peripheries of the lesions. The performance of the test in differentiating between melanomas and the naevi group comprising dysplastic, Spitz and Reed naevi was also good, with AUC=0.933±0.034 and 0.923±0.037 for the central and the border regions of the lesions, respectively. Using a more complex diagnostic algorithm also accounting for the staining intensity did not result in an improvement in the resolving power of the assay. A diagnostic algorithm using differences in the percentage fractions of cells expressing COX-2 may serve as a useful tool in aiding the differential diagnosis of 'histopathologically difficult' benign melanocytic skin lesions and early melanomas.