[The current situation of cancer morbidity and mortality in the light of the National Cancer Registry]. / A rákmorbiditás és -mortalitás jelenlegi helyzete a Nemzeti Rákregiszter tükrében.

In a previous issue of this journal the authors presented and summarized the basic objectives and tasks of the Hungarian National Cancer Registry positioned in an international environment. The recent publication is a continuation of the previous one. Based on the presentation and analysis of current statistical data, the public health background with the possible risk factors is examined. Considering changes in recent years, the mortality data are relatively stable, although slightly wavering. The trends are promising in some cancers (for example lip and oral cavity, breast, prostate cancers) however. Contrary to the barely changing nature of the total cancer deaths the number of annually reported new cases has increased significantly, which indicates a more effective role in both diagnostics and therapy. In light of the above, it is confirmed that the restructure of the national oncology care system and the European conformation is inevitable. Orv. Hetil., 2017, 158(3), 84-89.

[National Cancer Registry. Significance of a reliable database in the implementation of the required structural changes of cancer care in Hungary]. / Nemzeti Rákregiszter. A hiteles adatok gyujtésének jelentosége a hazai onkológiai ellátás szükségszeru szerkezetváltásában.

The authors summarize the basic objectives and scope of the Hungarian Cancer Registry. They review more than 100-year history of the national cancer database and its effects on current cancer data collection activities, which is outstanding in Europe. The compilation deals with the development of information technology, covers points of principle and practical issues such as parallel display and evaluation of mortality and morbidity statistics and their national and international importance concerning public health. The authors underline that reliable data collection and services of the National Cancer Registry are important for the society because they are public health issues with a critical importance for a better understanding of risk factors, prevention and patient care. Restructuring and European harmonization of the Hungarian cancer system are inevitable using a reliable information exchange and service, taking into account national specificities and international requirements.

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.

SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer.

BACKGROUND: Association between rectal or colon cancer risk and serine hydroxymethyltransferase 1 (SHMT1) C1420T or methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms was assessed. The serum total homocysteine (HCY), marker of folate metabolism was also investigated. METHODS: The SHMT1 and MTHFR genotypes were determined by real-time PCR and PCR-RFLP, respectively in 476 patients with rectal, 479 patients with colon cancer and in 461 and 478, respective controls matched for age and sex. Homocysteine levels were determined by HPLC kit. The association between polymorphisms and cancer risk was evaluated by logistic regression analysis adjusted for age, sex and body mass index. The population stratification bias was also estimated. RESULTS: There was no association of genotypes or diplotypes with colon cancer. The rectal cancer risk was significantly lower for SHMT1 TT (OR = 0.57, 95% confidence interval (CI) 0.36-0.89) and higher for MTHFR CT genotypes (OR = 1.4, 95%CI 1.06-1.84). A gene-dosage effect was observed for SHMT1 with progressively decreasing risk with increasing number of T allele (p = 0.014). The stratified analysis according to age and sex revealed that the association is mainly present in the younger (< 60 years) or male subgroup. As expected from genotype analysis, the SHMT1 T allele/MTHFR CC diplotype was associated with reduced rectal cancer risk (OR 0.56, 95%CI 0.42-0.77 vs all other diplotypes together). The above results are unlikely to suffer from population stratification bias. In controls HCY was influenced by SHMT1 polymorphism, while in patients it was affected only by Dukes' stage. In patients with Dukes' stage C or D HCY can be considered as a tumor marker only in case of SHMT1 1420CC genotypes. CONCLUSIONS: A protective effect of SHMT1 1420T allele or SHMT1 1420 T allele/MTHFR 677 CC diplotype against rectal but not colon cancer risk was demonstrated. The presence of SHMT1 1420 T allele significantly increases the HCY levels in controls but not in patients. Homocysteine could be considered as a tumor marker in SHMT1 1420 wild-type (CC) CRC patients in Dukes' stage C and D. Further studies need to clarify why SHMT1 and MTHFR polymorphisms are associated only with rectal and not colon cancer risk.

Deletions removing the last exon of TACSTD1 constitute a distinct class of mutations predisposing to Lynch syndrome.

Several different genetic alterations in the etiology of Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]) are known, mostly point mutations and genomic rearrangements in 1 of at least 3 mismatch-repair (MMR) genes. However, no susceptibility factor has yet been identified in a significant part (30-50%) of clinicopathologically well-defined HNPCC families, suggesting the presence of other predisposing mechanisms. In a set of probands from 27 Lynch syndrome families who lacked evidence of a germline mutation in either the MSH2 or MLH1 gene, we performed genomic deletion screening with the use of multiplex ligation-dependent probe amplification (MLPA) and sequencing. We used immunohistochemistry (IHC) and microsatellite instability (MSI) analyses on samples of the probands of all families. Comparative analysis of mRNA transcripts was performed on blood leukocyte-derived samples from mutation carriers and noncarrier controls. We report that large germline deletions encompassing the last exons of the TACSTD1 gene, upstream of MSH2, cosegregate with the HNPCC phenotype in 19% (5/27) of families tested. The tumors of the carriers show high-level MSI and MSH2 protein loss. We show that these deletions, by removing the transcriptional termination sequences of the upstream gene, give rise to multiple TACSTD1/MSH2 fusion transcripts. Our results provide evidence that deletions removing the last exon of TACSTD1 constitute a distinct class of mutations predisposing to Lynch syndrome. Thus, analysis of the 3' region of the TACSTD1 gene should be included in the routine mutation screening protocols for HNPCC.

[European and Hungarian national tasks in oncology]. / Európai és hazai kihívások az onkológiában.

It is well known that cancer incidence and mortality figures are very poor in Hungary. By providing the latest figures the authors analyze the epidemiological background and the risk factors responsible for this situation. Furthermore, based on international recommendations and national specificities, the authors define areas of action to solve this significant health issue. The main conclusion of their analysis is that it is inevitable to improve oncology care by adjusting it to European standards. The decade-old National Cancer Control Program (NCCP) is improved by incorporating legislative actions, educational issues, research and development priorities. The program now provides the definition of regional centers, recommend improvements of the function of oncology teams and rehabilitation. Based on successful European models, this program must be coordinated by the National Cancer Institute.

[The state of the colorectal screening in Hungary: lessons of the pilot programs]. / A népegészségügyi vastag- és végbélszurés helyzete Magyarorszagon: a mintaprogramok tanulsagai.

In Hungary, colorectal cancer is the second most common malignant disease. Due to its natural history, colorectal cancer is particularly suitable for screening. At present, epidemiological evidences of the effectiveness of detection of the symptomless colorectal cancer and its precursors are only available for the demonstration of fecal occult blood, endoscopic methods are also in use. For mass screening, fecal occult blood tests are recommended. Guaiac-type chemical methods are widely criticized because of the lack of specificity. Out of the emerging technologies, immunochemical methods based on the antigenicity of blood proteins (hemoglobin) seem to be the most suitable. In the model programmes organized in the frame of the National Public Health Programme, an immunochemical method using two blood proteins (hemoglobin and albumin) have been used. The compliance was not more than 30-45%. About one-third of those with positive blood test refused colonoscopy. The programmes revealed a great number of adenomatous polyps and early cancers, and in the way, the effectiveness of the method has been proved. The model programmes are still continued. Before the continuous and gradual extension of colorectal screening, the validity of the specific method needs to be tested and proved in order to be recognized as a routine procedure for screening. There is a need to test the feasibility of total colonoscopy, however, to this effect the colonoscopic capacity in the country has to be further developed.

[Trends in cancer mortality and morbidity in Hungarian and international statistics. Characteristics and potential outcome of public health screening programs]. / A hazai és nemzetközi daganatos halálozási és megbetegedési mutatók alakulása. A népegészségügyi programok jellegzetességei és várható eredményei.

This work is a comparative analysis of Hungarian and international cancer mortality and morbidity data with special attention to the epidemiological background of these indices. The authors also discuss the epidemiological reasons for a national public health screening program, its major objectives and the strategy of choice in relation to similar international programs. The recent cancer mortality and morbidity data including their trends are also provided.

[Tumour markers in malignant diseases]. / Rosszindulatú daganatok - tumormarkerek.

The authors define the concept of "tumour markers" that indicate the presence of malignant diseases and describe their various stages of development. In addition, they demonstrate the classification, selection and clinical application of these markers. The theoretical and practical aspects of their clinical use are also discussed in terms of national and international expectations. Shortcomings in the clinical use of tumour markers in Hungary are touched upon and recommendations are offered for tumour marker development in this country.

[Production and examination of double antigen specific immunoserum for immunochemical detection of occult blood]. / Két antigént felismerô immunszérum elôállítása és vizsgálata a rejtett bélvérzés immunkémiai kimutatásához.

OBJECTIVES: The authors have developed an immunochemical procedure and an immunisation method for the simultaneous detection of fecal hemoglobin and albumin to increase the screening effectiveness of colorectal cancers. METHODS: In the human specific blood testing, bispecific immunoserum recognising two antigens have been produced by glutardyaldehyde-hemoglobin-albumin makromolecule immunisation of goats. The purified and concentrated antiserum with double antibody specifity has been checked in a screening group of 1196 individuals aged over 40 years with Fecatest reservoirs. RESULTS AND CONCLUSIONS: The analytical sensitivity was proved 0.5 microg/ml for both proteins, which was greatly favourable for the screening. Furthermore, the intensity of the immunochemical reactions has grown, and it has increased the safety of the detection without decreasing the specificity. Because the number of the immunochemical tests that could be completed at the same time has been doubled (without excess of cost), this method has increased the effectiveness of the screening with taking care of expense.

[Role of tumour markers in monitoring and follow-up of colorectal cancer patients]. / A tumormarkerek szerepe a vastagés végbélrákos betegek követésében és ellenôrzésében.

The authors describe the significance of colorectal cancers in public health in Hungary and at international level. This is followed by the discussion of the latest aspects of patients' monitoring and continual follow-up with special emphasis on its clinical significance. In addition to CEA, the most important tumour marker in the present clinical practice, the authors review other tumour markers that might be used in controlling cancer treatment and patients' status. The estimation of treatment effectiveness should be combined with tumour marker level determinations at regular intervals because they are capable of demonstrating the dynamics of malignant processes and, if applied in adequate combinations, indicate the presence of a recurrence or metastasis. The integration of a "tumour marker panel" into the practice of follow-up may help early cancer detection and reduce health care expenses.

[Role of S100B protein in neoplasms and other diseases]. / Az S100B protein marker szerepe daganatokban és más kórképekben.

The S100 protein family constitutes the largest subgroup of the Ca binding proteins. To date 20 members of the family were discovered. S100 proteins regulate intracellular processes such as cell growth and motility, cell cycle regulation, transcription and differentiation. S100B protein is expressed constitutively by brain astrocytes. Serum S100B protein concentration in Stage II-III-IV melanoma is a reliable prognostic marker. The serum level of S100B protein is significant independent prognostic marker in respect to disease specific survival, it is a relevant marker for therapy monitoring and patient follow-up. It is recommended to determine the S100B expression pattern and intensity of the primary tumour of melanoma before therapy monitoring. Elevated S100B levels were published after head trauma, subarachnoidal haemorrhage and stroke. Furthermore, it indicates blood-brain barrier dysfunction. S100B protein was used to determine the cerebral damage after cardiovascular surgery as well.

[The role of tumor markers in the diagnosis and follow-up of liver tumors]. / Tumormarkerek a májdaganatok diagnosztikájában és a betegkövetésben.

A comprehensive survey on the tumour markers in the diagnosis and follow up of hepatocellular carcinoma (HCC) is given by the author. In addition to AFP, the "classical" HCC marker, other substances with potential clinical laboratory benefits are also described. The various marker combinations and the role of certain molecular "isoforms" are evaluated in terms of differential diagnosis of benignity/malignity. Since the long survival of patients with HCC depends primarily on successful liver resection the attention is directed to the significance of AFP mRNA, the predictive marker of recurring HCC.

hMLH1 and hMSH2 somatic inactivation mechanisms in sporadic colorectal cancer patients.

Much is known about the role of germline inactivation in mismatch repair (MMR) genes in hereditary non-polyposis colorectal cancer (HNPCC), but the impact of somatic MMR gene changes on sporadic colorectal cancer remains to be elucidated. In hereditary cases the hMLH1 and hMSH2 genes were shown to have a great importance, and in order to examine the somatic inactivation mechanisms of the two MMR genes hMLH1 and hMSH2 we screened 37 Hungarian sporadic colorectal cancer patients for allelic imbalance (AI), microsatellite instability (MSI), hMLH1 promoter hypermethylation and somatic mutations. Thirteen of the examined tumours (35%) were characterized by low-level MSI and none of the cases belonged to the high MSI group. Nine (24%) and seven (19%) cases had AI at the hMLH1 and hMSH2 genes, respectively. Seven tumours (19%) showed dense promoter hypermethylation of hMLH1, but only two patients had somatic mutations, one for each MMR gene. According to our study on this limited set of cases the most prominent mismatch repair inactivation mechanism in sporadic colorectal cancer patients is the hMLH1 promoter hypermethylation which may have a role in the carcinogenesis of sporadic colorectal cancer.

[Laboratory markers of melanoma progression]. / A melanoma progressziójának laboratóriumi markerei.

Extracellular tumour markers may have potential role in the follow-up of patients with malignant melanoma, in therapy monitoring and in prediction of prognosis. In our article circulating tumour markers in melanoma (melanoma inhibitory activity, lipid bound sialic acid, neuron specific enolase, TA90 immune complex, S-100B protein, 5-S-cysteinyldopa, tyrosinase, cytokines, metalloproteinases, LDH) were reviewed. Among laboratory melanoma markers the S-100B protein is the most investigated. S-100B protein has high specificity, appropriate sensitivity and proved to be significant prognostic factor independent from stages. High serum values are associated with shorter survival. However, before S-100B monitoring immunohistochemistry for the detection of S-100B is required. In the case of malignant melanomas with low expression serum S-100B monitoring may not be sensitive enough to follow disease progression. Although the serum concentration of 5-S-cysteinyldopa did not prove to be independent prognostic factor in our previous studies comprising the highest patient number in the literature, the marker was suggested for therapy monitoring. The survival analysis indicated that the elevated 5-S-cysteinyldopa level predicts shorter survival. In spite of the calculated low correlation between the two markers, parallel elevation of S-100B protein and 5-S-cysteinyldopa indicated shorter survival. On the basis of the literature LDH is the most appropriate tumour marker in stage IV to predict prognosis, but its sensitivity and specificity could not achieve that of S-100B protein. S-100B and LDH proved to be similarly reliable in respect to the clinical outcome. Determination of serum concentration of MIA and tyrosinase are also reliable markers in malignant melanoma. The other investigated markers are not well known yet or do not provide useful information to the clinicians.