DNMT1 and DNMT3B genetic polymorphisms affect the clinical course and outcome of melanoma patients.

The aberrant DNA methylation plays a critical role in a number of different malignancies, including melanoma. DNA methylation is catalyzed by DNA methyltransferases (DNMTs), involved in methylation maintenance (DNMT1) and de novo DNA methylation (DNMT3A and DNMT3B). The current study investigated the association of genetic variants in the DNMT1 and DNMT3B with the clinicopathologic features and the clinical course of melanoma patients. In the present study, DNMT1 (rs2228612, rs2228611, and rs2114724) and DNMT3B (rs406193 and rs2424932) polymorphisms were examined in 123 melanoma patients. Single nucleotide polymorphisms were assessed using TaqMan SNPs Genotyping Assays according to the manufacturer's protocols. The carriers of the variant genotype of DNMT1 rs2228612 had poorer overall survival and recurrence-free survival, (P = 0.000 and 0.000, respectively), and an increased risk for adverse outcome [hazard ratio (HR) = 6.620, 95% confidence interval (CI): 2.214-19.791, P = 0.001]. DNMT1 rs2228612 was also associated with ulceration (P = 0.045), nodal status (P = 0.030), progression (P = 0. 007), and stage of disease (P = 0.003). Univariate analysis indicated that tumor-infiltrating lymphocytes could be a marker of good prognosis in melanoma patients (HR = 0.323, 95% CI: 0.127-0.855, P = 0.025), whereas the genotype distribution of the DNMT3B rs406193 polymorphism correlated significantly with the presence of tumor-infiltrating lymphocytes (P = 0.012). The multivariate analysis showed that the DNMT1 rs2228612 polymorphism (HR = 12.126, 95% CI: 2.345-62.715, P = 0.003) is an independent predictor of poor overall survival in melanoma patients. As expected, disease progression was also found to be an independent prognostic factor in melanoma patients (HR = 37.888, 95% CI: 3.615-397.062, P = 0.002). DNMT1 rs2228612 was found to be an independent predictor of poor overall survival in melanoma patients. DNMTs polymorphisms could serve as a potential target for novel therapeutic approaches.

[Peripheral Primitive Neuroectodermal Tumor of the Small Bowel Mesentery - Report of a Case].

INTRODUCTION: Primitive neuroectodermal tumor or Ewing's sarcoma is a tumor of undifferentiated small round cells that arise from the soft tissues, and is believed to be of neural origin. It occurs most often in children, followed by adolescents and young adults. CASE OUTLINE: A case of a 24-year-old patient with ulcerostenosans Ewing's sarcoma of the initial part of the small intestine is presented in our paper. Reviewing the literature and using as an example the case of a female patient with signs of sideropenic anemia caused by primitive neuroectodermal tumor of the small intestine, an attempt was made to clarify the etiology, clinical presentation, diagnosis and therapy with the aim of its rapid detection and treatment. CONCLUSION: Mesenteric primitive neuroectodermal tumor is a rare neoplasm in adults, while it usually occurs in children and young adults. Surgical resection of the lesions with the application of chemotherapy is the main form of treatment of patients suffering from this disease.

[The importance of cytology in diagnosing rare breast carcinoma--two case reports].

INTRODUCTION: This paper presents two cases of very rare tumors of breast: breast sebaceos carcinoma, which has rarely been described in medical literature, and breast carcinosarcoma. Morphological characteristics and biological behavior of sebaceos carcinoma are still rather vague. Carcinosarcoma of the breast is a rare malignancy with distinct cell lines described as a breast carcinoma of ductal type with a sarcoma-like component. CASE REPORT: The first presented case is a 73-year-old female referred to our hospital in January 2008 with tumor of the right breast in the upper outer region of the breast and enlarged lymph nodes in the right axillary region. The second presented case is a 51-year-old female with carcinosarcoma, also a very rare primary breast tumor. She was admitted to our hospital in June 2011 with history of lump in the upper and lower outer quadrant of the left breast. In both cases, biopsy of tumor tissue was carried out with a thin needle, i.e. the aspiration cytology was applied as a diagnostic method, and during the operation the fast diagnostics of frozen sections and cytologic diagnostics were done. Although this methodology is important in diagnosis, in both cases it showed certain limitations in diagnosing such rare tumors. The final diagnosis was made after carefully synthesizing the histological findings and immunohistochemical phenotype. CONCLUSION: An accurate classification of breast tumors on cytological preparations is not possible in case of poorly differentiated and rare tumors. A careful and accurate classification of these tumors is necessary.