[Two Approaches to Cancer Development]. / Dva pohledy na vývoj nádoru.

BACKGROUND: The somatic mutation theory explaining the process of carcinogenesis is generally accepted. The theory postulates that carcinogenesis begins in a first renegade cell that undergoes gradual transformation from a healthy to a fully malignant state through the accumulation of genetic and epigenetic "hits". This theory focuses specifically on mutations and genetic aberrations, and their impact on cells. It considers tumors as populations of sick cells that lose control of their own proliferation. The theory was put forward by Robert Weinberg and Douglas Hanahan, and is the predominant view in current cancer biology. By contrast, the tissue organization field theory proposed by Carlos Sonnenschein and Ana Soto considers loss of physiological structure and function by a tissue as key events in tumor development. According to this theory, tumors arise at a tissue rather than at a cellular level. It is based on a presumption that proliferation status, rather than quiescence, is the default position of cells in multicellular organisms. AIM: The article aims to provide answers to following questions: Are the views of proponents of the somatic mutation theory (the reductionists) and proponents of the tissue organization field theory (the organicists) incompatible and incommensurable, even when the mainstream of tumor biology has shifted its attention from tumor cells toward the tumor microenvironment? Where to find a third interconnecting systemic approach? Is it useful to be aware of the controversy between reductionists and organicists? What this awareness contributes to? How do these alternative views influence practical oncology and tumor biology in general? CONCLUSION: Whether the true position is held by reductionists or organicists is unimportant. What is important is to be aware of the existence of these two concepts because this knowledge makes the way we think about tumor origin and development, and how we set up and interpret our experiments, more precise. KEY WORDS: carcinogenesis - mutation - cell - tissues - cell proliferation - cell quiescenceThis study was supported by grant of Internal Grant Agency of the Czech ministry of Health No. NT/13784-4/2012.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 29. 7. 2015Accepted: 27. 4. 2016.

Estimating cancer incidence, prevalence, and the number of cancer patients treated with antitumor therapy in 2015 and 2020 -  analysis of the Czech National Cancer Registry.

BACKGROUND: Cancer burden in the Czech population ranks among the highest worldwide, which introduces a strong need for a prospective modelling of cancer incidence and prevalence rates. Moreover, a prediction of number of cancer patients requiring active antitumor therapy is also an important issue. This paper presents the stage-specific predictions of cancer incidence and prevalence, and the stage- and region-specific patients requiring active antitumor therapy for the most common cancer diagnoses in the Czech Republic for years 2015 and 2020. The stage-specific estimates are also presented with regard to the treatment phase as newly diagnosed patients, patients treated for non-terminal recurrence, and patients treated for terminal recurrence. PATIENTS AND METHODS: Data of the Czech National Cancer Registry from 1977 to 2011 has been used for the analysis, omitting the records of patients diagnosed as death certificate only or at autopsy. In total, 1,777,775 incidences have been considered for the estimation using a statistical model utilizing solely the population-based cancer registry data. All estimates have been calculated with respect to the changing demographic structure of the Czech population and the clinical stage at diagnosis. RESULTS: Considering year 2011 as the baseline, we predict 89%, 15%, 31% and 32% increase in prostate, colorectal, female breast and lung cancer incidence, respectively, in 2020 resulting in 13,153, 9,368, 8,695, and 8,604 newly dia-g--nosed cancer patients in that year, respectively. Regarding cancer prevalence in 2020, the estimated increase is 140%, 40%, 51%, and 17% for prostate, colorectal, female breast and lung cancer, respectively, meaning that more than 100,000 prevalent female breast cancer patients as well as more than 100,000 prevalent prostate cancer patients are expected in the Czech Republic. The estimated numbers of patients requiring active antitumor therapy for prostate, colorectal, female breast and lung cancer in the Czech Republic in 2020 are 23,652, 14,006, 14,759 and 8,272; respectively. CONCLUSIONS: The analysis documents a serious increase in cancer incidence and prevalence in the Czech Republic in years 2015 and 2020 when compared to the situation in 2011. Regarding the estimated numbers of patients requiring active antitumor therapy, the model confirms a continuous increase that must be accounted for in the future planning of health care in the Czech Republic.

Cancer incidence and mortality in the Czech Republic.

BACKGROUND: The Czech Republic ranks among the countries with the highest cancer burden in Europe as well as worldwide. The purpose of this study is to summarize longterm trends in the cancer burden and to provide up-to-date estimates of incidence and mortality rates after 2011. DATA AND METHODS: The Czech National Cancer Registry (CNCR) was instituted in 1977 and contains information collected over a 34-year period of standardized registration covering 100% of cancer diagnoses within the entire Czech population. The CNCR analysis is supported by demographic data and by the Death Records Database. An overview of the epidemiology of malignant tumors in the Czech population is available online at www.svod.cz. RESULTS: All neoplasms, including nonmelanoma skin cancer, reached a crude incidence rate of almost 802 cases per 100,000 men and 681 cases per 100,000 women in 2011. The annual mortality rate exceeded 258 deaths per 100,000 individuals; in other words, more than 27,000 individuals die of cancer each year. The overall incidence of malignancies has increased with a growth index of +27.6% during the last decade (2001- 2011), while the mortality rate has been stabilized over the time span (growth index in 2001- 2011: - 5.0%). Consequently, the prevalence has significantly increased in the observed period and exceeded 475,000 cases in 2011. In addition to demographic aging of the Czech population, the cancer burden has also increased due to the growing incidence of multiple primary tumors (recently more than 15% of the total incidence). The most frequent diagnoses include colorectal cancer, lung cancer, breast cancer, and prostate cancer. Although some neoplasms are increasingly diagnosed at an early stage (e. g. the proportion of stage I or II was 75.3% for female breast cancer and 84.2% for skin melanoma), the numbers of early diagnosed cases are generally insufficient, even in the case of highly prevalent cancers such as colorectal carcinoma (only 46.1% of incident cases are diagnosed at stage I or II, according to recent data). CONCLUSION: Population-based data on malignant tumors are available in the Czech Republic. The data survey can help us define national cancer management priorities. The current priority is to achieve a sustained reduction of cases diagnosed at an advanced stage and reduction of the significant regional differences in diagnostic efficiency.

[Objective need for cancer prevention in the Czech Republic and Europe, and the state thereof]. / Objektivní potreba a stav nádorové prevence v Ceské republice a v Evrope

There is no doubt today of the need for cancer prevention. The growing incidence of cancer itself provides a sufficient justification for prevention programmes. A review of literature presented in this paper also documents the strong background of evidence-based cancer prevention programmes. The article also provides a critical analysis of the current status of primary cancer prevention and cancer screening in the Czech Republic in contrast with available international comparisons. Relevant international data have been obtained from the regularly repeated "Health at a Glance" studies (published by the OECD). Although the Czech Republic is one of the countries with the highest cancer burden in Europe, it has failed to develop and support a cancer prevention policy on a central level, and this also applies to smoking prevention. The Czech population needs an effective national strategy for the support of cancer prevention, as well as a strategy which would ensure equitable cancer care in terms of both quality and correct indication; a strategy which would be sustainable for at least 10 to 15 years to come.Key words: oncology - screening - risk factor - prevention - population burden This study was supported by the project 36/14//NAP "Development and implementation of methodology for the evaluation of effectiveness of personalised invitations of citizens to cancer screening programmes" as part of the pro-gram-me of the Czech Ministry of Health "National action plans and conceptions". The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE "uniform requirements" for biomedical papers.

[Epidemiology of screening-targeted cancers according to new data of the Czech National Cancer Registry]. / Epidemiologie zhoubných nádoru cílených screeningem dle nových dat Národního onkologického registru Ceské republiky.

The Czech Society for Oncology has developed an information system which combines the population-based Czech National Cancer Registry with clinical databases in order to cover the main areas of health care assessment - monitoring of the population burden, prediction of the number of cancer patients, diagnostic and treatment results. The presented data demonstrate a high cancer burden within the Czech population - each year there are approximately 8,000 new cases of colorectal cancer, 6,500 new cases of breast cancer, and 1,000 new cases of cervical cancer. And each year, about 4,000 people die from colorectal cancer, around 2,000 women die from breast cancer, and approximately 400 women die from cervical cancer in the Czech Republic. Population-based screening programmes focus on all of the above-mentioned groups of malignant tumours; therefore, it is essential to monitor epidemiological trends in order to assess the screening impact. Despite the high incidence rates of all three cancer types, the trend in mortality rates has been stable or has even decreased in the long term, which has inevitably led to a significant increase in the total prevalence of cancer patients. In 2011, the prevalence of colorectal cancer, breast cancer and cervical cancer amounted to 51,064 people, 67,261 women and 17,398 women, respectively. When compared with the year 2001, there was a 59%, 69% and 25% increase in the prevalence of colorectal cancer, breast cancer, and cervical cancer, respectively. Undoubtedly, taking care of high numbers of cancer patients will continue to require significant financial resources in the near future. As the epidemiological burden is still on the increase, preventive programmes need to be further promoted, including secondary prevention, which is provided through organised screening programmes. Although effective methods exist for timely diagnosis of all three of the above-mentioned cancer types, the epidemiological situation in the Czech Republic is being steadily worsened by a relatively high proportion of primary cancers being diagnosed too late. Each year, more than 50% of new colorectal cancer cases are diagnosed in clinical stage III or higher; in cervical cancer, this proportion is nearly 35%. By contrast, the well-promoted breast cancer screening programme has led to more than 75% of new cases of breast cancer being diagnosed in stages I or II, when the chance of successful treatment is significantly higher.

[Approach to population-based screening in the Czech Republic, methodology and first results of the personalised invitation of citizens to cancer screening programmes]. / Koncepce populacního screeningu v Ceské republice, metodika a první výsledky adresného zvaní obcanu do preventivních onkologických programu

In January 2014, a programme of personalised invitations was launched in the Czech Republic, with the objective of inviting insured persons to cancer screening programmes; namely breast cancer screening and cervical cancer screening in women, and colorectal cancer screening both in women and men. This programme aims at strengthening the current cancer prevention programmes, and to increase the currently inadequate participation of the target population in these programmes; therefore, personalised invitations are sent to citizens who have not participated in these programmes for several years and therefore at risk of developing a serious disease. The project is coordinated by the Czech Ministry of Health in cooperation with the expert medical societies involved (gynaecology, gastroenterology, gastrointestinal oncology, diagnostic radiology, general practice), representatives of health care payers, and other experts nominated by the Minister of Health. All health care payers invite their clients (insured persons) to preventive check-ups, covering all examinations needed. The project has been realised with the assistance of financial resources from EU funds. This article describes the methodology of personalised invitations which has been implemented nationwide, its data background, and the first results of the project in the first half of 2014, when almost 1.3 million Czech citizens were invited.

[Brazilian story of the R337H p53 mutation]. / Brazilský príbeh mutace p53 R337H.

The p53 tumor suppressor is an evergreen of molecular oncology. Since its discovery in 1979, it has been subjected to intensive investigation. The p53 protein is composed of "only" 393 amino acid residues, and function of almost each of them has been addressed in detail. Somatic mutations are extremely frequent, they can be found almost in each of the p53 codons and in all types of tumors. Inherited p53 mutations are rare but very penetrant, and they are typically associated with development of a broad spectrum of tumors. However, in 2001, the p53 research provided an unexpected discovery: the R337H allele was found in southern Brazil. This allele was atypically associated with only one type of tumor -  childhood adrenocortical carcinoma and it exhibited low penetrance. Therefore, new data on functioning and impact of the R337H mutation were highly desired. The results obtained during a few following years helped to elucidate not only this specific p53 variant but also provided insight into general principles of mutant p53 variants function. It also turned out that all R337H alleles that are very frequent in southern Brazil originate from one common ancestor.

[Doublehit lymphomas -  review of the literature and case report]. / Lymfomy se dvema zásahy -  prehled literatury a kazuistika.

UNLABELLED: Blymphocytes are cells of the immune system responsible for the antibody  mediated immune response. As estimated, a human body can produce as much as 1011 specific antibodies. There are no specific genes coding for every individual antibody in the human genome. Discrepancy between the huge diversity of antibodies and limited coding capacity of the genome is solved by combination of unique arrangement of genetic information for immunoglobulin and unique genetic and somatic processes providing this wide spectrum of antibodies. On one side, these mechanisms represent a life protecting source of a wide spectrum of antibodies but at the same time, they can be life threatening by raising the risk of a serious tumor disease, the B cell lymphoma. Double hit lymphomas represent a specific group of B cell lymphomas often featuring concurrent rearrangements of BCL2 and MYC genes. Activation of the MYC oncogene, typical for Burkitt lymphoma (BL), causes strong stimulation of cell proliferation. High activity of BCL 2, typical for follicular lymphoma, induces resistance to apoptosis. Concurrent damage of regulation of apoptosis and proliferation is probably responsible for the typical clinical manifestation of double hit lymphomas - aggressive course, resistance to conventional chemotherapy, high-risk of early relapse, short overall survival, frequent extranodal and central nervous system involvement. Recently, these lymphomas have attracted a strong attention of researchers as they provide sharp insights into processes of lymphocytes maturing and lymphomas development and highlight the double edged nature of mechanisms allowing the antibody broad diversity. CASE REPORT: Fifty  three year  old man was diagnosed with B cell lymphoma unclassifiable with features intermediate between diffuse large B cell lymphoma (DLBCL) and BL, based on morphology and immunophenotype. Fluorescent in situ hybridization analysis revealed double hit lymphoma diagnosis as the tumor cells bear t(14;18) translocation concurrently with the MYC gene rearrangement. The patient died five months after dia-gnosis.

Multivariate analysis of risk factors for testicular cancer: a hospital-based case-control study in the Czech Republic.

Growing incidence of testicular cancer around the world stimulates research attempting to explain the trends. This study quantified the contribution of different types of potential risk factors for testicular germ-cell cancer (TGCC) with differentiation between seminoma and non-seminoma. A standardized questionnaire containing demographic data, pre- and perinatal factors, social, lifestyle and occupational parameters was prepared. The data file consists of n = 356 TGCCs (seminoma: n = 195; non-seminoma: n = 161) and n = 317 controls, frequency matched on age to cases. The following factors were significantly associated with the risk of TGCCs in univariate analyses (ORs): atrophic testis (5.3), smoking over 12 pack-yr (4.9), cryptorchidism (2.9), testicular trauma (2.0), birth weight under 3,000 g (1.6), low degree of education (3.0) in correlation with manual occupation (2.3) and finally, overall familial cancer history (1.5) and familial history of breast (1.8) and prostate cancer (3.9). On the other hand, maternal age over 20 yr (OR < 0.4) and moderate recreational sport activity (OR = 0.5) significantly reduced the risk of TGCCs. A significant risk was associated with cryptorchidism (OR = 2.9; 95% CI = 1.5 - 5.9) where orchidopexy was delayed after 5 yr of age (OR = 5.2; 95% CI = 1.5-18.1). Delayed orchidopexy was associated namely with the risk of seminomas (OR = 7.5; 95% CI = 2.1-26.7). Only some of the variables were retained in multivariate model for TGCCs as well as for histological subtypes (multivariate adjusted OR for all TGCCs): atrophic testis (5.9), family history of prostate cancer (4.8), cryptorchidism (3.8) and interaction term 'low degree of education & manual occupation' (3.0). Familial history of breast cancer elevated risk of TGCCs and of seminomas (OR: 2.01 - 2.18). Birth weight under 3,000 g was retained in a multivariate model for TGCCs with a borderline significance (OR = 1.67). We could not rule out any type of risk factors, as each one was significantly represented in the final multivariate models. Familial cancer history remained to be an influential risk factor, altogether with some lifestyle and occupational parameters. This suggests that both environmental exposures and genetic inheritance can play role in the moderation of the risk of TGCC.

[Principle and importance of using the array CGH in hematooncology]. / Princip a význam metody arrayCGH v hemato-onkologii.

Identification of chromosomal changes and variation in DNA copy number allows us to understand pathogenesis of tumors. To the frequently diagnosed chromosomal changes belong acquired gains and losses of chromosomal regions carring genes involved in cellular proliferation and differentiation as well as oncogenes and tumor suppressor genes. The determination of gene changes is limited by techniques used for their identification. The introduction of genom-wide microarray technology, resolution has rapidly increased. Array comparative genomic hybridization (arrayCGH) offers higher resolution for genome-wide detection of chromosomal alteration and it is able to analyze hundreds to thousands of genes presented on microarray in one experiment. The aim of this study was to perform arrayCGH technology and to stress its value for the identification of chromosomal imbalances in hematological malignancies.

Complex karyotypes in childhood acute lymphoblastic leukemia: cytogenetic and molecular cytogenetic study of 21 cases.

Cytogenetic and molecular cytogenetic analysis of 79 childhood acute lymphoblastic leukemias (ALL) revealed chromosomal abnormalities in 76 (96%). Complex karyotypes (a finding of three and more chromosomal aberrations in a karyotype) were identified in 21 (26.6%) out of 79 patients. In 11 patients, complex karyotypes have included common recurrent chromosomal abnormalities, such as translocation t(12;21) in seven cases, t(9;22) in two cases, one case with t(2;1;19) and another one with translocation involving 11q23. In 10 patients, miscellaneous abnormalities were detected. Five patients displayed hyperdiploidy (47 approximately 57 chromosomes), three patients complex karyotypes with deletions of 9p, one patient with two new complex translocations t(2;4;12;13) and t(7;11;20), and the last patient with dic(12;21). The evaluation of the frequency of the chromosomal breaks (>5 per chromosome) showed that chromosomes 2, 4, 5, 7, 9, 12, 13, and 21 were most frequently affected. Survival analysis revealed statistically significant unfavorable event-free survival (EFS) (P=0.013) and decreased overall survival in the group with complex karyotypes (n=21) compared with the other cases (n=58). The evaluation of overexpression profile revealed increased occurrence of double CD13/CD33 positivity in patients with common recurrent chromosomal abnormalities (in 70% of cases); no such cases were registered in the other group (P<0.01).