Expression of Circulating miR-155, miR-21, miR-221, miR-30a, miR-34a and miR-29a: Comparison of Colonic and Rectal Cancer.

BACKGROUND: Colorectal cancer is an increasing cause of death. Circulating microRNAs (miRs) could be great diagnostic and prognostic biomarkers of colorectal cancer, but further continuation of their utility is needed for their comprehensive application. MATERIALS AND METHODS: Twenty-seven patients with colonic cancer, 16 with rectal cancer and 12 healthy volunteers as controls, were involved in this study. Expression of miR-155, miR-21, miR-221, miR-30a, miR-34a and miR-29a were determined by reverse transcription polymerase chain reaction (RT-PCR) from sera of patients. RESULTS: Expression of miR-155, miR-21 and miR-221 was significantly higher in rectal cancer than in colonic cancer. There was no difference found between those with TNM1 cancer and controls for both cancer types. miR-155, miR-34a and miR-29a were down-regulated in all patients with cancer compared to controls. We did not find any statistically significant up-regulation of miR-221 in patients with colonic cancer compared to controls. In contrast, in patients with rectal cancer, miR-221 expression was higher than in controls. Advanced stage was also linked to higher miR-221 expression compared to early stage. Slight, but statistically significant increase was observed in miR-30a expression in patients with colon cancer compared to control individuals. CONCLUSION: Our results partly support previous findings. Here we report on differences in the expression of circulating microRNA between colonic and rectal tumours for the first time.

[Investigating the predictive value of RMI and ROMA indices in patients with ovarian tumors of uncertain dignity]. / Az RMI- és a ROMA-index petefészekrákelõrejelzõ hatékonyságának vizsgálata adnextumorokban.

We were investigating the predictive value of RMI and ROMA indices in patients with ovarian tumors of uncertain dignity, in order to determine whether these methods are suitable for the early detection of ovarian malignancy. Our study included 162 patients treated at the Gynecological Department of the National Institute of Oncology (Budapest, Hungary). These patients were diagnosed with ovarian tumor of uncertain dignity, and were admitted to our Department with the purpose of gynecological surgery. Each of them had CA-125, HE4 blood tests and ultrasound scan in order to calculate RMI and ROMA indices and to study their effectiveness. In every case, the final type of surgery was determined by intraoperative frozen section examination results. Efficacy of RMI and ROMA indices was detected by the final histological examination taken from the same material that was sent for intraoperative frozen section. The sensitivity and specificity of RMI index was 82.0% and 85.1%, respectively, while ROMA index sensitivity and specificity was 88.5% and 72.3%. The results were better in postmenopausal women: RMI sensitivity had increased to 90.9% and specificity to 82.8%. ROMA index sensitivity reached 95.5% with a specificity of 60.7%. Thus premenopausal RMI sensitivity significantly decreased (58.8%), and specificity had surged (88.4%). In case of premenopausal ROMA results sensitivity had declined, though the results are much better than for RMI (70.6% vs. 58.8%), while specificity was 14% less than that of RMI (74.4% vs. 88.4%). According to our study, RMI and ROMA indices are good methods for identifying the dignity of malignant ovarian tumors. The sensitivity and specificity results are in accordance with international literature. Even though the premenopausal and postmenopausal values are different, RMI and ROMA tests complement each other and are excellent for predicting the dignity of a tumor. With the help of these indices 61 cases of malignancy were detected, which means that we have to operate only 3 patients in order to detect 1 case of malignancy.

Contribution of APC and MUTYH mutations to familial adenomatous polyposis susceptibility in Hungary.

Familial adenomatous polyposis (FAP) is a colorectal cancer predisposition syndrome with considerable genetic and phenotypic heterogeneity, defined by the development of multiple adenomas throughout the colorectum. FAP is caused either by monoallelic mutations in the adenomatous polyposis coli gene APC, or by biallelic germline mutations of MUTYH, this latter usually presenting with milder phenotype. The aim of the present study was to characterize the genotype and phenotype of Hungarian FAP patients. Mutation screening of 87 unrelated probands from FAP families (21 of them presented as the attenuated variant of the disease, showing <100 polyps) was performed using DNA sequencing and multiplex ligation-dependent probe amplification. Twenty-four different pathogenic mutations in APC were identified in 65 patients (75 %), including nine cases (37.5 %) with large genomic alterations. Twelve of the point mutations were novel. In addition, APC-negative samples were also tested for MUTYH mutations and we were able to identify biallelic pathogenic mutations in 23 % of these cases (5/22). Correlations between the localization of APC mutations and the clinical manifestations of the disease were observed, cases with a mutation in the codon 1200-1400 region showing earlier age of disease onset (p < 0.003). There were only a few, but definitive dissimilarities between APC- and MUTYH-associated FAP in our cohort: the age at onset of polyposis was significantly delayed for biallelic MUTYH mutation carriers as compared to patients with an APC mutation. Our data represent the first comprehensive study delineating the mutation spectra of both APC and MUTYH in Hungarian FAP families, and underscore the overlap between the clinical characteristics of APC- and MUTYH-associated phenotypes, necessitating a more appropriate clinical characterization of FAP families.

Alternatives for the intensive follow-up after curative resection of colorectal cancer. Potential novel biomarkers for the recommendations.

Early diagnosis of recurrence and metastasis of colorectal cancer following surgery of curative intent is of vital importance in terms of survival and quality of life. The consistent implementation of appropriate patient follow-up strategy is therefore essential. Debates over the methodology, evaluation and strategy of follow-up have been known for many years, and continue today. By introducing several follow-up models, the present paper offers different options featuring certain individual, national and international, conceptual and financial aspects. Colorectal cancer is an important public health concern due to its destructive nature and frequency, it is therefore essential to develop new monitoring strategies, involving new biomarkers and extensive clinical validation. Since the recurrence rate is very high in high-risk patients, the improvement of individual patient risk estimates and the utilization of a corresponding follow-up model require broad international co-operation and common practice, along with the determination of optimal levels of evidence.

[Need for developing a new strategy in the follow-up of colorectal cancer patients; the micro RNAs (miRNAs), as potential new biomarkers of early detection]. / Új követési stratégia kidolgozásának szükségessége a vastag- és végbélrákos betegek követésére; a mikroRNS-ek (miRNS) mint a korai felismerés lehetséges új biomarkerei.

In the mortality statistics of European countries colorectal cancers are known to assume the 2nd place after lung cancer. The mortality indices are particularly unfavourable in Hungary. Early detection is therefore of vital importance to the patient either the detection of the primary or recurrence after successful surgery is concerned. The latter is only feasible within a proper follow-up strategy. The present review focuses on follow-up due after surgical removal of the tumour with special emphasis on the efficacy of a new biomarker group (miRNAs) and their potential combination with the traditional markers. It is a model in the follow-up strategy that considers the results of risk assessment, as well. Since the methodology and strategy of follow-up are still controversial matters it is obvious that the development of a new follow-up strategy is imperative.

[A double immunochemical method for detecting faecal haemoglobin and albumin in rectal screening]. / Széklethemoglobin és -albumin kettos immunkémiai vizsgálat colorectalis szurésnél.

Undoubtedly, colonoscopy is the "gold standard" in the diagnosis of colorectal cancers. Sophisticated bowel preparation and risk of bowel perforation and bleeding, as well as the patient's discomfort during examination lead to low compliance in screening. Therefore, alternative non-invasive screening methods tend to come into the fore. In this study we compared the sensitivity and specificity of the double immunochemical FECA test for the haemoglobin + albumin content of the faeces with those of control colonoscopy in the detection of colorectal neoplasms. In a 3-year period 154 patients (69 males and 85 females) were scheduled for colonoscopy with previously collected stool samples. The sensitivity and specificity of the double immunochemical test for faecal haemoglobin + albumin content were determined in colorectal neoplasms of different severity. Colonoscopy served as a control examination. Colonoscopy identified in 77 cases benign lesions, and in 10 cases malignant tumours. The double immunochemical test for faecal blood and protein successfully used in model screening population showed in our present study 52.7% sensitivity and 92.3% specificity for significant neoplastic lesions (high-risk polyps and tumours). When the evaluation was limited to the high-risk polyps, the sensitivity was modified to 45.5% and the specificity to 92.3% and in case of invasive tumours to 90% and 100%, respectively. If only faecal haemoglobin content was measured, the overall sensitivity for polyps of any size and sort was 15.7% which, however, increased to 27.63% if faecal albumin was also measured. Based on relevant literature, the sensitivity of the FECA test for colorectal polyp and cancer is more favourable than that of other FITs. However, the increased sensitivity of the double faecal protein test falls short of the standard colonoscopy. Therefore, in certain cases the latter might be considered as a primary screening method.

The association of polymorphisms in 5-fluorouracil metabolism genes with outcome in adjuvant treatment of colorectal cancer.

AIM: The purpose of this study was to investigate whether specific combinations of polymorphisms in 5-fluorouracil (5-FU) metabolism-related genes were associated with outcome in 5-FU-based adjuvant treatment of colorectal cancer. METHODS: We analyzed two cohorts of 302 and 290 patients, respectively, one cohort for exploratory analyses and another cohort for validating the exploratory analyses. A total of ten polymorphisms in genes involved in 5-FU pharmacodynamics and pharmacokinetics were studied. End points were disease-free survival (DFS) and overall survival. Multifactor dimensionality reduction was used to identify genetic interaction profiles associated with outcome. RESULTS: Low-expression alleles in thymidylate synthase (TYMS) were associated with decreased DFS and overall survival (DFS:hazard ratio [HR] exploration 2.65 [1.40-4.65]; p = 0.004, HR validation 1.69 [1.03-2.66]; p = 0.03). A specific multifactor dimensionality reduction derived combination of dihydropyrimidine dehydrogenase and TYMS polymorphisms was associated with increased DFS (HR exploration 0.69 [0.49-0.98]; p = 0.04, HR validation 0.66 [0.45-0.95]; p = 0.03). Specific combinations of functional polymorphisms in DPYD and TYMS were demonstrated to be associated with DFS and overall survival in patients receiving adjuvant 5-FU-based treatment. Specifically high TYMS expression alleles seem to be associated with decreased DFS.

Metal levels in tissues of Eurasian otters (Lutra lutra) from Hungary: variation with sex, age, condition and location.

Liver samples of Eurasian otters from various parts of Hungary were analysed for mercury, copper, zinc, lead and cadmium. Only zinc concentration was significantly higher in females. Higher mercury and cadmium concentrations in adults and higher zinc values in immature otters were measured. Accumulation of mercury, copper and zinc in tissues increased with the declining condition of animals. Mercury and copper were detected with higher values in samples from large rivers.