PTEN mutations as predictive marker for the high-grade endometrial cancer development in slovak women.

Endometrial carcinoma (ECa) is one of the most common neoplasia of the female genital tract. The phosphatase and tensin (PTEN) homolog is the most frequently mutated tumor suppressor gene in endometrial carcinoma. PTEN encodes a phosphatase, a key regulatory enzyme involved in a signal transduction pathway that regulates cell growth, migration and apoptosis. The study evaluates an association between the morphological appearance of endometrial hyperplasia and ECa, and the presence of PTEN variations, PTEN protein´s level and intracellular localization. A total of 67 archived formalin-fixed and paraffin-embedded human biopsy tissue specimens with normal proliferative and secretory endometrium, endometrial hyperplasia without atypia and endometrial atypical hyperplasia, endometrioid the grade G1 and G3 and serous subtype of ECa were evaluated by sequencing for the presence of mutations in coding regions of PTEN gene of endometrial epithelial cells. The PTEN gene expression and intercellular localization of PTEN protein were evaluated immunohistochemically by immunoreactive score (IRS). PTEN mutation spectrum in endometrial carcinoma was identified for Slovak population. 28 non-silent mutations were identified in PTEN, twelve of them were novel, not annotated in Catalogue of Somatic Mutations in Cancer. Higher frequency of PTEN mutations was observed in serous carcinoma compared to global average. No correlation was observed between samples´ IRS, PTEN cellular localization and identified mutations. PTEN sequencing can be beneficial for patients considering prognosis of disease and sensitivity to treatment.

Importance of the genetics in the diagnostics of hydatidiform mole.

OBJECTIVE: To summarize the possibilities of the genetic analysis of hydatidiform moles and point out its perspectives in the diagnostics of this disease. DESIGN: Review. SETTING: Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Slovak Republic. METHODS: Analysis of published literature data from the internet databases PubMed, ScienceDirect, Scopus and printed literature from the period 1963-2019. RESULTS: This review refers on karyotyping, flow cytometry, FISH (Fluorescent in Situ Hybridization), VNTR-RFLP analysis (Variable Number of Tandem Repeats-Restriction Fragment Length Polymorphism), VNTR-PCR analysis (Variable Number of Tandem Repeats-Polymerase Chain Reaction) and STR (Short Tandem Repeat) genotyping of hydatidiform moles. The article summarizes possible application of these methods in the differential diagnostics of molar pregnancy (partial and complete hydatidiform moles) and nonmolar hydropic abortions. CONCLUSION: Genetic analyses offer precise identification of types of molar pregnancies when histopathological diagnosis is not clear during early stages of pathology.

MRI­based neoadjuvant therapy indication in middle and low rectal cancer.

OBJECTIVE: The aim of this study was to evaluate the indication of neoadjuvant therapy in patients with middle and low rectal cancer based on MRI examination. BACKGROUND: In spite of noticeable advances in the diagnosis of rectal cancer, the optimal treatment remains highly debated. Current guidelines advise the use of neoadjuvant therapy in UICC stage II patients or higher. However, in clinical praxis, there is gradual implementation of new criterions and variables used in rectal cancer stage evaluation, the fact of which influences the treatment choice. The most important emerging variables taken currently into account are the distance from mesorectal fascia, circumferential resection margin, extramural venous invasion and intersphincteric plane, all of which can be evaluated using the MRI examination. METHODS: The accuracy of MRI staging was compared with definite histopathological results from resected tumors. Patient data were prospectively collected between the years 2013 and 2018 at 3rd Surgical Clinic, Faculty of Medicine, Comenius University in Bratislava, Slovakia. Data from 101 patients were gathered and divided into two groups, according to the localization of tumor within rectum, while 9 patients were excluded from the study because of benign lesion diagnosis based upon final histopathologic evaluation. RESULTS: In 92 evaluated patients, no significant change was noted between MRI and histopathological T-staging. However, in N-staging, significant differences were noted between preoperative MRI staging and postoperative histopathological staging. CONCLUSION: The results of this study demonstrate inefficient preoperative lymph node staging, suggesting overtreatment of rectal cancer patients. Although the use of neoadjuvant therapy has led to great advances in modern cancer treatment, it is connected with a number of side effects and therefore should be indicated only for patients who can benefit from this treatment (Tab. 1, Fig. 3, Ref. 16).

Significance of MRI in rectal carcinoma therapy optimization - correlation of preoperative T- and N-staging with definitive histopathological findings.

In past decades, both prognosis and therapy of rectal cancer patients showed significant improvement, on the other hand, the incidence of rectal carcinoma continues to have a rising tendency. According to current UICC classification, patients in stage II rectal cancer or higher are indicated for neoadjuvant chemoradiotherapy (nCRT). Magnetic resonance imaging (MRI) is currently the most common diagnostic method used for preoperative staging of rectal cancer. Several studies already pointed out the inaccuracy of preoperative lymph node staging in patients with rectal cancer. The present study analyzed overall accuracy of MRI staging of rectal cancer and thus its accuracy in neoadjuvant therapy indication, by comparing preoperative MRI staging with definitive histopathologic results from resected tumors. This study evaluated cases of 92 patients with rectal tumor that underwent MRI examination followed by surgical resection. Tumors included in the analysis were ranging from T1 to T3b according to TNM staging, with free circumferential resection margin (CRM), distance form mesorectal fascia more than 5 mm, negative intersphincteric plane and also negative extramural venous invasion (EMVI), while the N stage was not decisive. In all cases both N-staging and T-staging were evaluated histologically and compared with preoperative MRI results. Significant difference in preoperative and postoperative N-staging was shown in 51 patients (61.45%). In majority of cases MRI lead to overstaging, which was observed in 44 cases (53.1 %), with complete negativity of lymph nodes proven by histological examination in 34 cases. On the other hand, understaging of lymph nodes was observed only in 7 cases (7.4 %). The T-staging did not show significant differences. Results from this study confirm that MRI plays an important role in T-staging of rectal tumors, however, there are admittedly issues in N-staging of tumors, which should lead to reevaluation of neoadjuvant therapy indication in patients with positive lymph nodes according to MRI examination. Based on the results of this study, we see the future of preoperative staging of rectal tumors in precise T-staging together with accurate assessment of CRM and distance of tumor from mesorectal fascia as well as evaluation of intersphinteric plane and EMVI.

Cardiac telocytes as principal interstitial cells for myocardial reparation and regeneration after infarction - our hope.

According to our knowledge, this is the first research experiment that focuses on the study of the distribution of c-kit positive cells at the sites of myocardial infarction in human hearts (Fig. 3, Ref. 16).

Early versus delayed laparoscopic cholecystectomy in treatment of acute cholecystitis.

BACKGROUND: Acute cholecystitis is one of the most frequent diseases occurring in the developed countries of the world. Since the advent of laparoscopic cholecystectomy there has been a lack of agreement regarding the timing of the operation in the treatment of acute cholecystitis. METHODS: From September 2012 to January 2015 we carried out a prospective randomized trial at the IIIrd Surgical Department of University Hospital Milosrdní bratia in Bratislava. The aim of the trial was to compare the two basic approaches of the treatment of acute cholecystitis. During our trial, 62 patients with acute cholecystitis were admitted to the surgery department and 31 patients were treated with an early laparoscopic cholecystectomy within 72 hours after the appearance of the symptoms. Other 31 patients were primarily treated with antibiotics and subsequently underwent a delayed cholecystectomy after 6-8 weeks. RESULTS: Our results suggest several advantages of the early laparoscopic cholecystectomy such as shorter operation time, lower conversion rate, shorter length of hospital stay, shorter postoperative convalescence and lower cost of hospitalization. CONCLUSION: According to these results we believe that immediate laparoscopic cholecystectomy (within 24 hours from the patient's admission to hospital) should become a preferred method of treatment of the patients with acute cholecystitis (Tab. 1, Fig. 2, Ref. 17).

Importance of thymectomy and prognostic factors in the complex treatment of myasthenia gravis.

BACKGROUND: Thymectomy is indicated in patients with seropositive myasthenia gravis (SPMG) in patients under the age of 50 and in patient with myasthenia gravis (MG) associated with thymoma. METHODS: 345 patients with MG who underwent an extended thymectomy from April 1990 to December 2010. Patients were separated into the 4 groups: group with a complete stable remission, pharmacological remission group, group of patients with significant improvement and the group with mild improvement of symptoms. RESULTS: In our study, we observed 345 patients with MG and thymectomy. 137 patients (39.71 %) attained the complete stable remission (CSR) and 92 patients (26.67 %) the pharmacological remission (PR). The significant improvement of MG symptomatology was achieved in 95 patients (27.54 %). The rest of 21 patients from total 345 (6.08 %) have reached only a mild improvement. Patients after thymectomy with CSR were in the clinical stage I and IIA, in accordance to the modified Osserman classification and most benefited from the thymectomy. CONCLUSIONS: The extended thymectomy combined with immunotherapy is the preferred treatment with an expected satisfactory long-term remission rate. Despite the recent improvements in MG medical therapy, thymectomy plays an important role in the otherwise complex treatment of the disease. Because of early diagnosis with thymectomy performed without a delay, patients can achieve significantly more often favorable outcomes and even stable remissions (Tab. 4, Fig. 7, Ref. 17).

[Optimal timing of laparoscopic cholecystectomy in treatment of acute cholecystitis]. / Optimálne nacasovanie laparoskopickej cholecystektómie v liecbe akútnej cholecystitídy.

INTRODUCTION: Acute cholecystitis is one of the most frequent diseases occurring in developed countries of the world. Laparoscopic cholecystectomy is a treatment option for acute cholecystitis. Since the advent of laparoscopic cholecystectomy there has been a lack of agreement regarding the timing of the operation in the treatment of acute cholecystitis. METHOD: From September 2012 to August 2015 we carried out a prospective randomized trial at the IIIrd Surgical Department of University Hospital Milosrdní bratia in Bratislava. We compared two basic approaches to the treatment of acute cholecystitis. During the trial, 64 patients with acute cholecystitis were admitted to the surgery department. 32 patients were treated with early laparoscopic cholecystectomy within 72 hours from the appearance of the symptoms. The other 32 patients were primarily treated with antibiotics and subsequently underwent delayed cholecystectomy after 68 weeks. RESULTS: Our results suggest several advantages of early laparoscopic cholecystectomy such as shorter operation time, lower conversion rate, shorter length of hospital stay, shorter postoperative convalescence and lower cost of hospitalisation. CONCLUSION: Based on these results we believe that immediate laparoscopic cholecystectomy (within 24 hours from the patients admission to hospital) should become a preferred method of treatment of patients with acute cholecystitis. KEY WORDS: acute cholecystectomy early and delayed laparoscopic cholecystectomy prospective randomized trial.

[Results of gestational trophoblastic neoplasia treatment in the Slovak Republic in the years from 1993 to 2012]. / Výsledky liecby gestacnej trofoblastovej neoplázie v Slovenskej republike v rokoch 1993 az 2012.

OBJECTIVE: Analysis and epidemiology of gestational trophoblastic neoplasia treatment in the Slovak Republic in the years 1993-2012. DESIGN: Retrospective epidemiological national study. SETTING: Centre for gestational trophoblastic disease Ministry of Health the Slovak Republic, Bratislava. METHODS: Retrospective analysis results of gestational trophoblastic neoplasia treatment according to prognostic scoring and staging system FIGO/WHO in Centre for gestational trophoblastic disease Ministry of Health the Slovak Republic Bratislava in the years 1993-2012. RESULTS: The treatment of gestational trophoblastic neoplasia (GTN) in the Czech and Slovak Republics started in 1955 and lasted till 1993. After the split of the former Czechoslovakia the Centre for gestational trophoblastic disease was created in Slovakia. 75 patients were treated in this Centre in the years 1993-2012. According to prognostic scoring and staging system FIGO/WHO 56 (75%) patients had low-risk gestational trophoblastic neoplasia and 19 (25%) of patients had high-risk gestational trophoblastic neoplasia. There were 41 patients (55%), 2 (3%), 24 (32%) and 8 (11%) in stage I., II., III. and IV. respectively. Total curability rate was 94.7% and mortality rate was 5.3%. Curability rate 100% was achieved in stage I & II and all placental site trophoblastic tumours (PSTT), 98.3% in stage III and 50% stage IV. In the years 1993-2012 the incidence of choriocarcinoma was one in 76 273 pregnancies and one in 53 203 deliveries. The incidence of other gestational trophoblastic neoplasia in the same years was for PSTT one in 533 753 pregnancies and one in 372 422 deliveries, invasive mole one in 145 611 pregnancies and one in 101 569 deliveries, and persistent GTN one in 40 043 pregnancies and one in 27 932 deliveries. 225-241 patients were treated in the same period of time in the Czech Republic with curability rate 98.2-98. 3%. CONCLUSION: Early detection and treatment in the centre for trophoblastic disease are crucial points in the manage-ment of gestational trophoblastic neoplasia, because the effective therapy of gestational trophoblastic neoplasia with high curability rate is available.

Relationship between circulating tumor cells and epithelial to mesenchymal transition in early breast cancer.

BACKGROUND: Circulating tumor cells (CTCs) play a crucial role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients. Epithelial to mesenchymal transition (EMT) is involved in cancer invasion and metastasis. The aim of this study was to assess correlation between CTCs and expression of EMT transcription factors TWIST1 and SLUG in breast tumor tissue. METHODS: This study included 102 early BC patients treated by primary surgery. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoietic cells using RossetteSep™ negative selection kit. RNA extracted from CD45-depleted PBMC was interrogated for expression of EMT (TWIST1, SNAIL1, SLUG, FOXC2 and ZEB1) and epithelial (KRT19) gene transcripts by qRT-PCR. Expression of TWIST1 and SLUG in surgical specimens was evaluated by immunohistochemistry and quantified by multiplicative score. RESULTS: CTCs were detected in 24.5 % patients. CTCs exhibiting only epithelial markers were present in 8.8 % patients, whereas CTCs with only EMT markers were observed in 12.8 % of pts and CTCs co-expressing both markers were detected in 2.9 % pts. We observed lack of correlation between CTCs and expression of TWIST1 and SLUG in breast cancer cells or cancer associated stroma. Lack of correlation was observed for epithelial CTCs as well as for CTCs with EMT. CONCLUSIONS: In this translational study, we showed a lack of association between CTCs and expression of EMT-inducing transcription factors, TWIST1 and SLUG, in breast tumor tissue. Despite the fact that EMT is involved in cancer invasion and metastasis our results suggest, that expression of EMT proteins in unselected tumor tissue is not surrogate marker of CTCs with either mesenchymal or epithelial features.

PTEN sequence analysis in endometrial hyperplasia and endometrial carcinoma in Slovak women.

Phosphatase and tensin homolog (PTEN) is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa). ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree of PTEN alterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3), complex hyperplasia (5), atypical complex hyperplasia (7), endometrioid carcinomas G1 (20) and G3 (5), and serous carcinoma (5) were evaluated for the presence of mutations in coding regions of PTEN gene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar.

Evaluation of protein expression and DNA methylation profiles detected by pyrosequencing in invasive breast cancer.

Breast carcinoma is the most common cancer with high mortality caused by metastatic disease. New molecular biomarkers predicting the tumour's metastatic potential would therefore improve metastasis prevention and personalised care. The aim of the study was to investigate the relationship between DNA methylation levels in invasivity and metastasising associated genes with aberrant protein expression and also to evaluate whether a similar DNA methylation level is present in the tumour and circulating cell-free DNA for utilising plasma DNA methylation as prognostic biomarker. By using pyrosequencing, we analysed DNA methylation levels of 11 genes, namely APC, ADAM23, CXCL12, ESR1, PGR B, CDH1, RASSF1A, SYK, TIMP3, BRMS1 and SOCS1 in tumour, plasma and peripheral blood cells from 34 patients with primary breast cancer, as well as plasma and peripheral blood cells from 50 healthy controls. Simultaneously, the expression of related proteins in paraffin-embedded tumour samples was evaluated by immunohistochemistry. Statistical analysis was performed by SPSS statistics 15.0 software. Tumour DNA hypermethylation was found in most commonly methylated RASSF1A (71.9%), APC (55.9%), ADAM23 (38%) and CXCL12 (34.4%) genes with methylation levels up to 86, 86, 53 and 64 %, respectively. In tumours, significantly higher methylation levels were found in nine genes, compared with the patients´ peripheral blood cell DNA. Furthermore, in patients methylation levels in peripheral blood cell DNA were significantly higher than in controls in CXCL12, ESR1 and TIMP3 genes, but the values did not exceed 15%. On the other hand, no correlations were observed in patients between DNA methylation in tumours and cell-free plasma DNA. Moreover, in patients and controls nearly identical values of cumulative DNA methylation (43.6 % ± 20.1 vs. 43.7 % ± 15.0) were observed in plasma samples. A variable spectrum from high to none expressions presented in tumour tissues in all of the proteins evaluated, however in APC and CXCL12 genes a visible decreasing trend of mean DNA methylation level with increasing expression of the corresponding protein was observed. The DNA methylation profiles manifested in our group of breast carcinomas are cancer specific, but they are not the only cause that affects the silencing of evaluated genes and the decrease of relevant protein products. The clinical utility of DNA methylation testing in peripheral blood cell DNA for cancer diagnosis and therapy need to be further investigated.

[Expression of p57 marker in differential diagnosis of complete and partial mole - correlation with DNA analysis]. / Expresia markeru p57 v diferenciálnej diagnostike kompletnej a parciálnej moly - korelácia s DNA analýzou.

Nowadays valid classification of gestational trophoblastic disease, according to the World Health Organisation from the year 2003, divides gestational trophoblastic disease into three groups - molar pregnancies, non-neoplastic non-molar changes of trophoblast and tumours of trophoblast. To the molar pregnancies belong complete, partial, invasive and metastatic hydatidiform mole. In the differential diagnosis it is important to distinguish the complete hydatidiform mole from other forms of gestational trophoblastic disease, because there is an increased risk of malignant transformation of trophoblast cells in complete hydatidiform mole. 10 cases of genetically confirmed diploid complete mole and 10 cases of genetically confirmed triploid partial mole were included into our retrospective study. All cases were examined microscopically in the basic haematoxillin and eosin staining and immunohistochemically with the use of antibodies against human choriogonadotropin hormone, placental alkaline phosfatase and protein p57. Villous cytotrophoblast, stromal villous cells, extravillous trophoblast and decidual cells were p57 positive in all cases of partial hydatidiform mole. All 10 cases of complete hydatidiform mole were p57 negative in stromal villous cells and villous cytotrophoblast. P57 protein is a marker distinguishing complete hydatidiform moles from partial moles.

[The viewpoint of an internist on the problem of an aortoenteric fistula]. / Pohlad internistu na problematiku aortoenterálnej fistuly.

Aortoenteric fistula is an uncommon life-threatening disease; it can be divided into primary and secondary one. Primary aortoenteric fistula is the result of ongoing disease in the aorta and the intestine, secondary one is iatrogenic. Typical symptoms are abdominal pain and gastrointestinal bleeding (two-stage process). The most appropriate diagnostic method is CT aortography, treatment is only surgical. 75-year-old patient was admitted to the 5th Department of Internal Medicine in Bratislava due to progression of renal parameters, the patient had undergone an aortofemoral bypass 4 years ago. During the fourth day of his hospitalization the patient had a massive hematochezia with a shock state. After transient stabilization of the patient, 30 minutes after the first hematochezia, a massive hematemesis appeared and then the patient died. An autopsy has confirmed the secondary aortic-enteral fistula between the duodenum and the aneurysm arising from the aortofemoral bypass.

Sertoli-Leydig cell tumor of the ovary--morphological and immunohistochemical analysis.

Sertoli-Leydig cell tumor is a rare and usually unilateral tumor of the ovary occurring in women's reproductive age. Only about 10% of these patients are over 50 years of age. One third of these patients are suffering from signs of virilisation. This work summarizes the morphological and immunohistochemical characteristics of this tumor in a 56-year old woman with clinical signs of virilisation.

A comparative study of EGFR mutation screening methods in non-small cell carcinoma of lung.

Epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase of the ERBB2 family that has important roles in the proliferation and metastasis of tumor cells. It is frequently overexpressed in common solid tumors and has become a favored target for orally administered small-molecule tyrosine kinase inhibitors (TKI) and monoclonal antibody-based therapy. Gain-of-function somatic mutations of the EGFR tyrosine kinase domain have been associated with the response of some patients with non-small-cell lung carcinoma to TKIs. We evaluated three methods of EGFR mutation analysis to identify an optimal assay for clinical testing based on comparison of diagnostic sensitivity, technical difficulty, and cost (Tab. 1, Fig. 1, Ref. 12).

Perspectives and complexity of an experimental cancer study. the secrets of tumorigenesis. (To the Gupta's, Chaffer's and Weinberg's "perspectives" and to the nurse's "horizons").

We would like to add to the "mysteriousness", our observations from the application of "identical" BP6 cells either intraperitoneally or subcutaneously. In connection with the concept that tumor development is not only a portrayal of cells proliferation, we could presume that different "environment" will result in structurally different tumors. Morphological differences observed are not significant, but they are present (Fig. 2, Ref. 12). Full Text (Free, PDF) www.bmj.sk.

The role of molecular biology in detection and monitoring of prostate cancer.

The study of molecular markers in various types of human carcinomas, as well as in carcinoma of prostate, is focused on genes responsible for the formation of carcinoma. Mutation, amplification or other changes in these genes or in their protein products are being examined and compared with traditional prognostic markers. These genes can be characterized as oncogenes, tumor suppressor genes or genes for other significant cell functions. However, studies are often limited by heterogenity and multifocality of tumors, especially in prostate cancer. In this review, we offer a survey of some of the most frequent diagnostic and prognostic parameters of molecular biology research in relation to prostate cancer.

Does incorporation of gene for green fluorescent protein in BP6 fibrosarcoma tumor cells depress their intraperitoneal growth in rats? (In honour of Nobel Prize laureates 2008--Osamu Shimomura, Martin Chalfie, Roger Y. Tsien).

This manuscript was in honour of Nobel Prize in chemistry "for the discovery and development of the green fluorescent protein, GFP" to Osamu Shimomura, Martin Chalfie, and Roger Y. Tsien, simultaneously a brief information about experience with GFP in experimental tumorigenesis used this study is also presented. The experimental data have showed that BP6 cells incorporated with GFP gene have had smaller ability to induce both experimental intraperitoneal and subcutaneous tumor process. It was anticipated that incorporation of GFP gene might change physiological properties of cytoskeleton and worsen adhesive characteristics of tumor cells. It was also supposed that aftertime GFP will enable to monitor proliferation of cells not only within experimental work, but also in human medicine. GFP could help (supposedly) as reporter of proliferation, but also can serve as "target" for guide of tumorigenesis inhibiting substances. These ideas which are consequences of our experiments we append as congratulation to Nobel Prize in chemistry of the 2008 (Fig. 2, Ref. 44). Full Text (Free, PDF) www.bmj.sk.

[The complexity of interactions of the tumour growth process]. / Komplexita interakcií nádorového procesu.

It was believed for rather a long time that the only components of tumour tissue are transformed cells characterised by hyper-proliferation, invasivity and immortalisation. Therapeutic strategies thus focused on autonomous proliferation and tumour cell survival. These result from oncogene activation and inactivation of tumour-suppressor genes. Research studies showed that tumour growth itself is a complex process. In addition, studies confirmed involvement of heterotypical multicellular interactions in tumour tissue. Complexity as a characteristic is one of the processes that do not demonstrate attributes of linear systems. The process of tumour growth involves certain patterns that cannot be classified according to duration and sequence. Consequently, tumour growth can be viewed as a process with features typical for complexity. From this perspective, tumour environment consists of a range of cells, such as endothelial cells and their progenitor cells, pericytes, fibroblasts, tumour-associated fibroblasts, myofibroblasts, smooth muscle cells, mast cells, T- and B-lymphocytes, neutrophils, eosinophils, basophils, NK-cells and several different forms of macrophages. At present, well-founded assumptions exist that in-depth study of intra-tumour environment might lead to formulation of new principles in tumour biology as well as introduction of new therapeutic strategies. Research into details oftumour microenvironment is needed to expand scientific knowledge as well as to, subsequently, define tumour biomarkers. Monitoring of these biomarkers will facilitate molecular diagnostics. Biomarkers will be widely used to monitor tumour growth as well as to monitor the process of treatment. Monitoring of combinations of biomarkers will enable more detailed characterisation of tumour microenvironment. These might include, apart from receptors, signal molecules, growth factors and molecules accelerating apoptosis, specific molecules as well as their combinations or neoangiogenesis or tumour innervation parameters. Tumour complexity involves not just intracellular environment but also intracellular relationships and associations between cells and extracellular tumour components. Detection of circulating tumour cells represents another parameter to be monitored. Low-molecular weight fluorescent dyes will very likely be used for their detection. It can be assumed that circulating tumour cells will be used as markers of prognosis as well as indicators of malignity progression and treatment. Scientific advances in this area will facilitate individualised therapy of patients suffering from cancers. The aim of the present review study was to analyze scientific knowledge from the perspective of acceptance of complexity and heterogeneity of each tumour. We perceived processing of the vast amounts of literature as meaningful with respect to recognition of new knowledge and theoretical preparation for expected changes in diagnostics and treatment of tumours. We believe that the presented findings are a useful step towards achievement of comprehensive insight into tumour microenvironment.