Evaluation of the clinical value of the newly identified urine biomarker HIST1H4K for diagnosis and prognosis of prostate cancer in Bulgarian patients.

PURPOSE: Searching for diagnostic and prognostic biomarkers for prostate cancer (PC) is main public health priority. DNA methylation in body fluids is a stable, easily detectable and promising PC biomarker. The major advantages of urine-based assays are their noninvasive nature and the ability to monitor PC with heterogeneous foci. The aim of this study was to determine the diagnostic value of the recently identified candidate PC biomarker HIST1H4K. METHODS: We investigated DNA methylation of HIST1H4K in urine samples from 57 PC patients, 29 controls with benign prostatic hyperplasia (BPH) and 50 young asymptomatic men (YAM) by MethyLight real-time PCR. RESULTS: The frequency of HIST1H4K promoter hypermethylation significantly discriminated PC patients from YAM (AUC =0.763; 95% CI 0.672-0.839; p<0.0001), but did not show any statistical difference between PC patients and BPH controls (AUC=0.513, 95% CI 0.402-0.622; p=0.8255). HIST1H4K could not outperform the prostatic specific antigen (PSA) in our sample (AUC=0.785; 95% CI 0.679-0.870; p<0.0001). Methylation of HIST1H4K showed significant correlation with aging (r=0.5418; p<0.0001), but with no other clinicopathological characteristics. CONCLUSION: The results suggest that the promoter hypermethylation of HIST1H4K is rather due to aging than related to prostate carcinogenesis. To elucidate this observation analysis of larger samples is needed.

Extranodal marginal zone B-cell lymphoma arising in chronic myeloid leukaemia successfully treated with tyrosine kinase inhibitor: a case report.

BACKGROUND: Chronic myelogenous leukemia (CML) is a hematological malignancy that originates in an abnormal pluripotent bone marrow stem cell. CML is consistently associated with the expression of the BCR-ABL1 fusion gene, generated by the t(9;22) chromosomal translocation, thus creating the Philadelphia chromosome, a target for protein tyrosine kinase inhibitor (TKI) therapy.  There is no published data, demonstrating increased risk for development of second cancers, associated with the exposure to TKIs. CASE REPORT: We report a case of a primary extranodal marginal zone B-cell lymphoma (EMZBCL), diagnosed in a 53-year-old woman with CML receiving treatment with TKI the preceding seven years. Both diagnoses were confirmed by cytological/histological examination. Regarding CML, complete hematological, cytogenetic, and molecular remission was achieved by imatinib therapy. Regarding EMZBCL complete remission with an anthracycline-based polychemotherapy was achieved, while the patient was on continuous treatment with imatinib. Currently, the patient is in major molecular response for CML (151 months) and also in complete remission for EMZBCL (60 months). CONCLUSION: We report this case as we consider that any secondary neoplasia developing in patients treated with TKIs should be reported for assessment and further detailed analyzes. Hippokratia 2016, 20(3): 241-243.

[Evaluation of level of expression of p16 (INK4a) in endocervical lesions of uterine cervix].

UNLABELLED: The incidence of malignant and premalignant endocervical glandular lesions is increasing. Several research groups have recently used the protein p16 (INK4a) as a possible diagnostic biomarker of cervical cancer. The objects of study were to evaluate whether the specificity of p16 (INK4a) expression in is sufficient for distinguishing normal, dysplastic and neoplastic endocervical epithelium. MATERIALS AND METHODS: Paraffin-embedded samples of diagnostic biopsies and surgical materials were used. Control group included biopsy samples from 10 patients with normal findings. We examined 20 samples with different pathologic endocervical lesions. Monoclonal antibody against p16 was used (DAKO). RESULTS: In control samples we did not find any p16 (INK4a)-positive cells. Overexpression of p16 (INK4a) was detected in samples of cervical dysplasia and invasive carcinomas. CONCLUSIONS: Overexpression of the protein p16 (INK4a) is typical for dysplastic and neoplastic epithelium of cervix uteri. p16 (INK4a) may be regarded as a supplementary test for routine diagnostics of cervical lesions.

Macrophageal infiltration and microvessel density in laryngeal carcinoma: study of 52 cases.

Angiogenesis is one of the six originally constituted hallmarks of cancer that has been extensively studied in the last two decades. The aim of our study is to assess the microvessel and macrophageal density in laryngeal carcinoma and its clinicopathological correlations. We immunohistochemically assessed microvessel density (CD34) and macrophage count (CD68) using microarray techniques and then looked for clinicopathological correlations. The mean micro-vessel density in the study group was 14.27 ± 12.92 vessels in a ×200 field with a mean macrophageal infiltration density of 5.19 ± 4.32. Median microvessel density was significantly higher in patients with metastasis than in patients without metastasis. Additionally, linear regression established that macrophageal infiltration density could predict microvessel density in laryngeal carcinoma. We found no association between either factor and recurrence rate or other clinical characteristics. Our study adds additional data to a problem that has been widely studied during the last two decades, even if controversies in this area still remain.