Circulating HPV DNA in patients with cervical precancerous lesions and cervical cancer.

OBJECTIVE: In our review article we focused on the circulating HPV DNA and its potential role in the pathogenesis of cervical cancer and in the evaluation of patients´ prognosis with cervical cancer Design: The article is a systematic review study analyzing available scientific articles focused on the circulating HPV DNA. SETTING: Clinic of Obstetrics and Gynecology, Jesenius faculty of Medicine in Martin, Comenius University in Bratislava, Slovakia. METHODS: In our study we searched the medical database PubMed with the key words: circulating HPV DNA, cervical cancer, cervical precanceroses. The core of our work is focused on the scientific articles published in English language since year 1995. RESULTS: We identified 13 studies in PubMed database analyzing the circulating HPV DNA in the process of cervical carcinogenesis. It is clear from the results that circulating HPV DNA is a significant prognostic marker of cervical malignant diseases including the early stages. CONCLUSION: The results focused on circulating HPV DNA show the significance of molecular biology in assessing the prognosis of cervical cancer. This idea has to be supported by further relevant studies. The uniformity of studies and use of the most sophisticated methods could help to answer the question about the real role of circulating HPV DNA in the process of cervical carcinogenesis and disease progression.

Epigenetics: an alternative pathway in GISTs tumorigenesis.

Many diseases have different pathological backgrounds responsible for abnormal cell behavior and exhibiting altered function and signal transduction. This is especially true for tumors and although changes affecting DNA sequence, irreversible mutations and chromosomal aberrations in gastrointestinal stromal tumors (GISTs) have been widely studied, the importance of reversible epigenetic changes increasingly recognized in many cancers has received insufficient attention in these tumors. Epigenetic mechanisms are part of normal development and gene expression under normal conditions, but malfunction of these processes leads to malignant transformation by disturbing both intra- and intercellular communication. GISTs are a specific group of gastrointestinal tract tumors resistant to conventional chemotherapy and radiotherapy. Although they account for only 1% to 2% of tumors, they are among the most widespread gastrointestinal mesenchymal tumors. DNA hyper/hypomethylation overexpression/underexpression of miRNAs or abnormal histone modification may provide an alternative to the genetic modifications responsible for GIST pathology, response to treatment, prognosis and overall survival. This review summarizes the known epigenetic mechanisms involved in GIST pathogenesis; including onset, progression, and GISTs resistance. Reversible epigenetic changes are a novel and appropriate approach to halt the spread of metastases and the emergence of resistance in GIST treatment, and these changes depend on the type of epigenetic alternation, including inhibitors of histone acetyltranferase and deacetylase and DNA methyltransferases.

Determination of malignant potential of cervical intraepithelial neoplasia.

Basic diagnostic procedures in cervical cancer screening are able to set the diagnosis but they do not provide any information about the biological nature and behavior of lesions. The causal link of HPV infection and cervical cancer and discoveries of complex interactions between host and HPV genome opened new possibilities in molecular diagnostics. HPV DNA analysis, determination of viral load, detection of E6 and E7 mRNA transcripts, identifying of methylation profiles, genomic changes, miRNAs, and telomerase activity should be the right choice for exact diagnostics and prediction of behavior of premalignant lesions of the cervix. These findings set a completely new light not only in diagnostic but also in management and treatment of cervical dysplasia and cervical cancer.

[Correlation between the incidence of PIK3CA mutations in breast cancer and histopathological characteristics of the tumor]. / Korelácia výskytu PIK3CA mutácií v karcinóme prsníka s histologickými vlastnostami nádoru.

OBJECTIVE: To determine the presence of mutations in exon 9 (encoding the helical domain) and exon 20 (encoding the kinase domain) of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene in DNA obtained from paraffin embedded tissue from patients with carcinoma of the mammary gland and to correlate results with clinicopathological characteristics of cancer. DESIGN: Prospective clinical study. SETTING: Department of Molecular Biology, Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Commenius University, Martin, Slovak Republic. METHODS: In set of 95 tissue samples from patients with breast cancer, mutations in exon 9 and 20 were analysed by sequencing. We also observed the associations between mutations and histopathological characteristics of tumor. RESULTS: Overall, mutations were present in 25.3% (24/95) of PIK3CA gene, of this 14.7% (14/95) of mutations were located in exon 9 and 10.5% (10/95) of mutations were in exon 20. We detected three "hotspot" mutations, two were located in exon 9 (E542K, E545K) and the third mutation was found in exon 20 (H1047R). Mutations in exon 9 showed significant correlation with lower grade(p = 0.0074) and pN status without metastases(p = 0.0415). Mutations in exon 20 were associated with higher age of patient (p = 0.0249). The E545K mutation correlated with lower grade (p = 0.0013) and pN status (p = 0.0232) particularly; the H1047R mutation was significantly more frequent in lobular type of breast cancer (p = 0.0354). CONCLUSION: The PI3K signaling pathway plays a critical oncogenic role in the development of human breast cancer and the prevalence of its deregulation advocates its potential as a feasible therapeutic target. In our study we demonstrate a significant correlation between the presence of PIK3CA mutations and some clinicopathological characteristics of tumour. We have shown that the mutations in exon 9 of PIK3CA were associated with favourable prognostic factors. KEYWORDS: "hotspot" mutation, PIK3CA, PI3K pathway, breast cancer.