Stage IIA Skin Melanoma Treatment With ECHO-7 Oncolytic Virus Rigvir.

Melanoma is a global problem due to the rising numbers of skin melanoma cases. Current treatment guidelines for patients with stage IIA melanoma recommend only observation after surgery. In this report, the authors describe a patient with stage IIA skin melanoma treated with surgery and Rigvir virotherapy. Two years after the patient discovered a brown spot on the right cheek, surgery was indicated because the mass had started to ulcerate. Rigvir virotherapy was applied both before and after surgery. Observations made more than 7 years after surgery indicated no signs of disease progression. This case report illustrates an early treatment approach. Neoadjuvant treatment for early-stage melanoma is gaining more interest in both scientific and medical communities; therefore, the authors believe it is relevant to share their observations.

Correlation of Soluble CD44 Expression in Saliva and CD44 Protein in Oral Leukoplakia Tissues.

The aim of this study was to determine whether and how pan-CD44 protein expression in leukoplakia tissues correlates with positive SolCD44 test presence and their role in oral leukoplakia. SolCD44 and total protein expression in saliva were determined using an OncAlert® Oral Cancer Rapid test. Comparison of paired associations of total protein, SolCD44, mean number of CD44 expressed epithelial layers in leukoplakia tissue, and macrophages below the basement membrane between control group and patients with leukoplakia showed statistically significant results (p < 0.0001). It is shown that the total protein indicates low or elevated risk of possible malignant transformation processes in leukoplakia. Statistically significant differences between higher total protein level and clinical forms of oral leukoplakia (p < 0.0001), as well as CD44-labeled epithelial cell layer decrease (p < 0.0001), were found. This possibly points to the onset of the stemness loss in leukoplakia tissue. CD9 antigen expression in the exosomes of the oral epithelium explained the intercellular flow of SolCD44 and other fluids in the leukoplakia area. We conclude that the OncAlert® Oral Cancer Rapid test is a valuable screening method in daily clinical practice, in terms of complementing clinical diagnostics methods and to assess the potential for early malignancy.

Meta-Analysis of Cancer Triploidy: Rearrangements of Genome Complements in Male Human Tumors Are Characterized by XXY Karyotypes.

Triploidy in cancer is associated with poor prognosis, but its origins remain unclear. Here, we attempted to differentiate between random chromosomal and whole-genome origins of cancer triploidy. In silico meta-analysis was performed on 15 male malignant and five benign tumor cohorts (2928 karyotypes) extracted from the Mitelman Database, comparing their ploidy and combinations of sex chromosomes. A distinct near-triploid fraction was observed in all malignant tumor types, and was especially high in seminoma. For all tumor types, X-chromosome doubling, predominantly observed as XXY, correlated strongly with the near-triploid state (r ≈ 0.9, p < 0.001), negatively correlated with near-diploidy, and did not correlate with near-tetraploidy. A smaller near-triploid component with a doubled X-chromosome was also present in three of the five benign tumor types, especially notable in colon adenoma. Principal component analysis revealed a non-random correlation structure shaping the X-chromosome disomy distribution across all tumor types. We suggest that doubling of the maternal genome followed by pedogamic fusion with a paternal genome (a possible mimic of the fertilization aberration, 69, XXY digyny) associated with meiotic reprogramming may be responsible for the observed rearrangements of genome complements leading to cancer triploidy. The relatively frequent loss of the Y-chromosome results as a secondary factor from chromosome instability.

Originally misdiagnosed rhabdoid tumour of the kidney. A case report and differential diagnosis.

Rhabdoid tumour of the kidney (RTK) is considered to be one of the most aggressive neoplasms of early life. The histogenesis of RTK still remains a matter of controversy. Immunohistochemistry usually shows diffuse reactivity for vimentin, focal reactivity to the epithelial marker, variable expression of mesenchymal and neuroectodermal markers, and loss of INI1 protein staining. Expression of the Wilms' tumour protein (WT1) was described in the RTK cases. We would like to present a case of rhabdoid tumour of the kidney in Latvia, which caused diagnostic difficulties of a 27-month-old girl, and a short review of literature.

Assessment of V600E mutation of BRAF gene and rate of cell proliferation using fine-needle aspirates from metastatic melanomas.

BACKGROUND: metastatic melanomas are incurable by systemic treatment and it is therefore of the highest concern to develop new therapeutic regimens. RAF kinases play a key role in the RAS-RAF-MAPK signalling pathway which mediates cellular response to growth signals. An inhibitor of the RAS-RAF-MAPK cascade, sorafenib, has shown promising therapeutic results in treatment of several types of metastatic tumours. It can be hypothesized that metastatic melanomas with activating BRAF mutation may respond to RAF kinase-blocking therapy. The objective of the study was to analyze if the activating BRAF V600E mutation is present in metastatic melanomas. MATERIALS AND METHODS: Fine-needle aspirates from 44 metastatic melanomas were studied. The V600E mutation in exon 15 of the BRAF gene was selected for genotyping. A Taq-Man MGB biallelic discrimination system was used. Immunocytochemical assessment of the Ki-67 antigen was used to analyze the growth fraction of cells. RESULTS: Nearly 39% of metastatic melanomas had BRAF V600E mutation. Tumours with BRAF V600E mutation had a tendency to have a more aggressive clinical course. The growth fraction showed correlation with tumour progression. This study indicates that the V600E mutation is present in metastatic melanomas and occurs more often in sites without chronic sun exposure. Mutated tumours may have a more aggressive clinical course since such melanomas metastasize at an earlier stage. Determination of the BRAF mutation and the growth fraction of melanomas may add a prognostic value. CONCLUSION: A fraction of melanoma cases possess an activating BRAF mutation and may benefit from RAF-kinase inhibitor treatment. Future studies are needed to confirm this hypothesis.

Immunohistochemical analysis of the S100A1, S100B, CD44 and Bcl-2 antigens and the rate of cell proliferation assessed by Ki-67 antibody in benign and malignant melanocytic tumours.

Malignant melanomas usually have an unfavourable prognosis and poor response to chemotherapy. Deregulation of cell proliferation, programmed cell death and intercellular interactions are among several important mechanisms that might lead to malignant transformation of melanocytes and melanoma progression. The S100A1, S100B, Bcl-2 and CD44 antigens have all been described as being involved in different processes of melanoma progression. The expression of these antigens, as well as the rate of cell proliferation, was analyzed retrospectively in melanocytic tumours from 126 patients (32 males and 94 females, age ranging from 11 to 91 years). The series included benign (45 intradermal, 27 compound and eight displastic naevi) and malignant (39 primary and 14 metastatic) melanocytic tumours. The proliferating rate assessed by Ki-67 staining was lower in naevi than in melanomas, with a correlation coefficient of r = 0814. There was no overlap for rate of proliferation between benign and malignant tumours. The expression of S100A1 was low in benign melanocytic tumours and increased in malignant melanomas (r = 0.61). In contrast, a higher percentage of S100B antigen-positive cells were observed in benign melanocytic lesions than in melanomas (Pearson correlation coefficient, 0.627). In addition, positive immunostaining for S100B antigen in malignant melanomas corresponded with the areas with increased proliferating rate. The expression of Bcl-2 was lower in melanomas than in benign melanocytic tumours (r = -0.53). Bcl-2-negative areas within melanomas had an increased proliferating rate. The expression of CD44 showed a large variation both in benign and malignant melanocytic tumours. CD44 antigen expression was higher in melanomas with known metastases than in those without metastases, but this difference was not statistically significant.

Expression of the CD117, COX-2 and HSP90 antigens and cell proliferation in fine-needle-aspirated cells from metastatic melanomas.

BACKGROUND: Blocking therapies aimed at COX-2, HSP90 and CD117 have been described recently. The objective of the study was to analyze expression of these antigens and the proliferation rate in metastatic melanomas. MATERIALS AND METHODS: Fine-needle aspirates from 30 patients were analyzed. Immunocytochemical methods were applied to assess COX-2, HSP-90 and CD117. Cell proliferation was analysed using expression of Ki-67. Findings were compared with histopathological parameters. RESULTS: All cases expressed COX-2 and HSP90. CD117 was expressed in 46% of cases. The proliferation index ranged between 7% and 54%. No correlation was found between histological properties of the primary tumours and expression of CD117, COX-2 and HSP90 in their metastases. An inverse correlation was found between HSP90 and MIB-1 index. CONCLUSION: A large proportion of metastatic melanomas expressed COX-2 and HSP90. This may have a clinical implication for blocking therapy of the corresponding molecules. Expression of CD117 antigen was observed in only 5/30 melanoma cases. We hypothesize that such melanomas may benefit from targeted therapy with kinase inhibitors.

CDKN2A and CDK4 variants in Latvian melanoma patients: analysis of a clinic-based population.

Germline mutations of the CDKN2A and CDK4 genes explain a significant proportion of familial melanoma. To date, there have been few published estimations of the prevalence of such mutations in sporadic melanoma patients. In this study, we investigated CDKN2A and CDK4 exon 2 for germline mutations in 125 consecutive cutaneous malignant melanoma patients recruited through the Latvian Oncological Center, using amplicon melting analysis and sequencing. No disease-related CDKN2A germline mutations were identified in any of the melanoma patients analysed but the previously described CDK4 mutation, Arg24His, was found in one patient with a family history of melanoma. CDKN2A polymorphisms were studied as putative low penetrance susceptibility genes. The proportion of cases with polymorphisms in this Latvian melanoma population was Ala148Thr (c.442G>A) (6%), 500 C/G (c.*29C>G) (18%), and 540 C/T (c.*69C>T) (20%); however, only the frequency of the Ala148Thr polymorphism was higher in melanoma patients than in 203 controls (6 versus 1%, P=0.03). Ala148Thr has also been reported in association with melanoma in a Polish series but not in an English series. We therefore examined the Ala148Thr carrier's haplotype in 10 Latvian and 39 Polish samples. No significant difference was seen between these populations and the predominant haplotype observed in English samples, giving no indication that the discrepancy could be explained by population differences in linkage disequilibrium. In summary, our results show that germline mutations at the CDKN2A locus are rare in sporadic melanoma in Latvia. The study does, however, provide some additional evidence for a role for the CDKN2A polymorphism Ala148Thr as a low penetrance susceptibility gene. The detected CDK4 exon 2 mutation was found in only the seventh family identified worldwide with a germline CDK4 mutation.