Primary retroperitoneal mucinous cystadenocarcinoma in pregnancy - case report.

INTRODUCTION: Primary retroperitoneal mucinous cystadenoma (PRMC) and its malignant variant - cystadenocarcinoma are extremely rare tumors known only from case studies and reviews. PRMC is a cystic tumor of the retroperitoneum, which remains asymptomatic for a long time and can reach significant proportions. It occurs mainly in women. CASE REPORT: We present the case of a 38-year-old healthy woman with diagnosed resistance in the right mesogastrium during a c-section. The delivery was terminated without a surgical intervention. The above mentioned resistance was examined further by ultrasound, computed tomography and magnetic resonance imaging. All imaging examinations showed a solid - cystic bilocular expansion, which looked like a mesenteric cyst in the right paracolic area. The patient was asymptomatic at all times, with only a palpable resistance of the abdominal wall. In November 2020, the patient underwent an elective surgery - extirpation of the cystic tumor and prophylactic appendectomy. The operation was performed classically, via midline laparotomy without perioperative perforation of the cystic tumor and without complications in the postoperative period. The histopathological examination showed a malignant variant of PRMC. So far, the patient remains free of any problems and is followed at the department of oncology. CONCLUSION: The goal of treatment is to achieve complete surgical removal of the tumor without its perioperative perforation. Due to the rare occurrence of the disease, there are no guidelines for the diagnosis and treatment of PRMC. Precisely because PRMC is a rare tumor, it should be part of the differential diagnosis of cystic tumors of the retroperitoneum, especially when young women are concerned.

Association of triple positivity with prognostic parameters and overall survival in a population-based study of 6,122 HER2-positive breast cancer patients: analysis of real-world clinical practice based on a research database.

Triple-positive breast cancer (TPBC), i.e. HER2-positive (HER2+) and hormone receptors-positive breast cancer, is a specific subgroup of breast cancers. TPBC biology is characterized by strong mutual interactions between signaling pathways stimulated by estrogens and HER2 amplification. The present study aims to carry out a population-based analysis of treatment outcomes in a cohort of hormone receptor (HR) positive and negative breast cancer patients who were treated with anti-HER2 therapy in the Czech Republic. The BREAST research database was used as the data source for this retrospective analysis. The database covers approximately 95% of breast cancer patients treated with targeted therapies in the Czech Republic. The analysis included 6,122 HER2-positive patients. The patients were divided into two groups, based on estrogen receptor (ER) or progesterone receptor (PR) positivity: hormone receptor negative (HR-) patients had both ER- and PR-negative tumors (n=2,518), unlike positive (HR+) patients (n=3,604). HR+ patients were more often diagnosed premenopausal at the time of diagnosis, presented more often at stage I or II and their tumors were less commonly poorly differentiated. The overall survival (OS) was significantly higher in subgroups of HR+ patients according to treatment setting. When evaluated by stages, significantly higher OS was observed in HR+ patients diagnosed at stages II, III, and IV and regardless of tumor grade.

Analysis of DNA methylation and microRNA expression in NUT (nuclear protein in testis) midline carcinoma of the sinonasal tract: a clinicopathological, immunohistochemical and molecular genetic study.

The aim of this study was a detailed clinicopathological investigation of sinonasal NUT midline carcinoma (NMC), including analysis of DNA methylation and microRNA (miRNA) expression. Three (5%) cases of NMC were detected among 56 sinonasal carcinomas using immunohistochemical screening and confirmed by fluorescence in situ hybridization. The series comprised 2 males and 1 female, aged 46, 60, and 65 years. Two tumors arose in the nasal cavity and one in the maxillary sinus. The neoplasms were staged pT1, pT3, and pT4a (all cN0M0). All patients were treated by radical resection with adjuvant radiotherapy. Two patients died 3 and 8 months after operation, but one patient (pT1 stage; R0 resection) experienced no evidence of disease at 108 months. Microscopically, all tumors consisted of infiltrating nests of polygonal cells with vesicular nuclei, prominent nucleoli and basophilic cytoplasm. Abrupt keratinization was present in only one case. Immunohistochemically, there was a diffuse expression of cytokeratin (CK) cocktail, CK7, p40, p63, and SMARCB1/INI1. All NMCs tested negative for EBV and HPV infection. Two NMCs showed methylation of RASSF1 gene. All other genes (APC, ATM, BRCA1, BRCA2, CADM1, CASP8, CD44, CDH13, CDKN1B, CDKN2A, CDKN2B, CHFR, DAPK1, ESR1, FHIT, GSTP1, HIC1, KLLN, MLH1a, MLH1b, RARB, TIMP3, and VHL) were unmethylated. All NMCs showed upregulation of miR-9 and downregulation of miR-99a and miR-145 and two cases featured also upregulation of miR-21, miR-143, and miR-484. In summary, we described three cases of sinonasal NMCs with novel findings on DNA methylation and miRNA expression, which might be important for new therapeutic strategies in the future.

HPV Status and Mutation Analysis Using Multiparallel Sequencing in Distal Oesophageal and Gastro-oesophageal Junction Adenocarcinomas.

The incidence of adenocarcinoma of oesophagus or gastro-oesophageal junction is increasing in Europe and other regions of the Western world. Research of possible causes has shifted to the molecular level. This study evaluated human papillomavirus (HPV) using real-time PCR and mutational status of selected genes using the multiparallel sequencing method (NGS) in DNA extracted from paraffin-embedded tumour tissue of 56 patients with oesophageal or gastro-oesophageal junction adenocarcinoma. The genetic material was in sufficient quality for the analysis in 37 cases (66 %). No HPV-positive sample was found. NGS revealed higher frequency of mutations in TP53, ARID1A, PIK3CA, SMAD4, ERBB2, MSH6, BRCA2, and RET genes. Association between gene mutations and histological grade, subtype according to Lauren, or primary tumour site was not statistically significant. In conclusion, the study did not confirm any HPV-positive sample of oesophageal and gastro-oesophageal junction adenocarcinoma. The study confirmed the usefulness of NGS analysis of paraffin-embedded tissue of these tumours, and it could be used in clinical studies to evaluate the prognostic and/or predictive value of the tested mutations. The association between gene mutations and histological features should be tested in larger patient cohorts.

[Malignant Melanoma - from Classical Histology towards Molecular Genetic Testing]. / Maligní melanom - od klasické histologie k molekulárne genetickému testování.

BACKGROUND: Malignant melanoma is - in comparison with other skin tumors - a relatively rare malignant neoplasm with highly aggressive biologic behavior and variable prognosis. Recent data in pathology and molecular diagnostics indicate that malignant melanoma is in fact not a single entity but a group of different neoplasms with variable etiopathogenesis, biologic behavior and prognosis. New therapeutic options using targeted treatment blocking MAPK signaling pathway require testing of BRAF gene mutation status. This helps to select patients with highest probability of benefit from this treatment. AIM: This article summarizes information on the correlation of morphological findings with genetic changes, discusses the representation of individual genetic types in various morphological subgroups and deals with the newly proposed genetic classification of melanoma and the current possibilities, pitfalls and challenges in BRAF testing of malignant melanoma. It also describes the current testing situation in the Czech Republic - the methods used, the representation of BRAF mutations in the tested population and the future of testing. It also shows the limitations of the BRAF and MEK targeted treatment concept resulting from the heterogeneity of the tumor population. Mechanisms of acquired resistance to MAPK pathway inhibitors, possibilities of their detection, and issues of combination of targeted therapy and immunotherapy are discussed.Key words: malignant melanoma - BRAF - mutation - molecular targeted therapy - tumor microenvironment - tumor heterogeneity This work was supported by projects PROGRES Q40/11, BBMRICZ LM2015089, SVV 260398 and GACR 17-10331S. 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: 28. 3. 2017Accepted: 16. 5. 2017.

[Technical background of data collection for parametric observation of total mesorectal excision (TME) in rectal cancer]. / Technické zajistení sberu dat pro parametrické sledování totální mezorektální excize (TME) pro karcinom rekta.

INTRODUCTION: Improvement in any human activity is preconditioned by inspection of results and providing feedback used for modification of the processes applied. Comparison of experts experience in the given field is another indispensable part leading to optimisation and improvement of processes, and optimally to implementation of standards. For the purpose of objective comparison and assessment of the processes, it is always necessary to describe the processes in a parametric way, to obtain representative data, to assess the achieved results, and to provide unquestionable and data-driven feedback based on such analysis. This may lead to a consensus on the definition of standards in the given area of health care. METHOD: Total mesorectal excision (TME) is a standard procedure of rectal cancer (C20) surgical treatment. However, the quality of performed procedures varies in different health care facilities, which is given, among others, by internal processes and surgeons experience. Assessment of surgical treatment results is therefore of key importance. A pathologist who assesses the resected tissue can provide valuable feedback in this respect. RESULTS: An information system for the parametric assessment of TME performance is described in our article, including technical background in the form of a multicentre clinical registry and the structure of observed parameters. CONCLUSION: We consider the proposed system of TME parametric assessment as significant for improvement of TME performance, aimed at reducing local recurrences and at improving the overall prognosis of patients. KEY WORDS: rectal cancer total mesorectal excision parametric data clinical registries TME registry.

[Parametric monitoring of the quality of total mesorectal excision and surgical treatment of rectal carcinoma results of a multicenter study]. / Parametrické sledování kvality totální mezorektální excize a chirurgické lécby karcinomu rekta výsledky multicentrické studie.

INTRODUCTION: Tumour size and the quality of its complete surgical removal are the main prognostic factors in rectal cancer treatment. The number of postoperative local recurrences depends on whether the mesorectum has been completely removed - total mesorectal excision (TME) - and whether tumour-free resection margins have been achieved. The surgery itself and its quality depend on the accuracy of preoperative diagnosis and detection of risk areas in the rectum and mesorectum, on the surgeons skills, and finally on pathological assessment evaluating whether complete tumour excision has been accomplished including circumferential margins of the tumour, and whether mesorectal excision is complete. The aim of our study was to implement and standardize a new method of evaluation of the quality of the surgical procedure - TME - in rectal cancer treatment using an assessment of its circumferential margins (CRO) and completeness of the excision. METHODS: The study consisted of two parts. The first, multi-centre retrospective phase with 288 patients analysed individual partial parameters of the diagnosis, operations and histological examinations of the rectal cancer. Critical points were identified and a unified follow-up protocol was prepared. In the second, prospective part of this study 600 patients were monitored parametrically focusing on the quality of the TME and its effect on the oncological treatment results. RESULTS: The proportion of patients with restaging following neoadjuvant therapy increased from 60.0% to 81.7% based on preoperative diagnosis. The number of specimens missing an assessment of the mesorectal excision quality decreased from 52.9% in the retrospective part of to the study to 22.8% in the prospective part. The proportion of actually complete TMEs rose from 22.6% to 26.0%, and that of nearly complete TMEs from 10.1% to 24.0%. CONCLUSION: The introduction of parametric monitoring into routine clinical practice improved the quality of pre-treatment and preoperative diagnosis, examination of the tissue specimen, and consequently improved quality of the surgical procedure was achieved. KEY WORDS: rectal cancer TME - parametric monitoring - quality control.

Results of retrospective classification of thyroid FNAs according to the Bethesda system: would this have improved accuracy?

OBJECTIVES: To retrospectively reclassify the results of fine needle aspiration (FNA) cytology at our institution according to the Bethesda system for reporting thyroid cytopathology (TBSRTC), and to determine whether the introduction of the new classification system would have influenced the diagnostic accuracy compared with our existing system in which suspicious/indeterminate categories (categories III-IV) are managed according to clinical findings and cytopathologists' recommendations. METHODS: FNAs performed under ultrasound guidance between 2001 and 2012, and subsequently verified by histology or repeat FNA and follow-up, were reviewed and retrospectively reclassified according to TBSRTC. RESULTS: Among a total of 1310 histologically verified FNAs, the positive predictive values (%) for malignancy and neoplasia (carcinoma + follicular adenomas) for category I-VI according to the TBSRTC were 5.7/11.3, 2.6/5.5, 14.4/34.2, 23.6/55.0, 57.0/64.5 and 92.2/94.2, respectively. Although all the categories predict malignancy closely, the difference in malignancy rate between categories III and IV was not statistically significant; however, the difference in total neoplasia rate reached statistical significance. When patients with cytological and clinical follow-up were included, the malignancy rated dropped in category I to 2.4%, whereas, in category III, it remained at 13%. Repeat FNA instead of direct surgery spared half of the patients from surgery. The cytopathologists' recommendations for histological verification in category III were associated with an insignificant increase in malignancy rate, but the total neoplasia rate reached 57.5%. CONCLUSIONS: At our institution, the application of the TBSRTC did not improve the diagnostic accuracy for the detection of malignancy compared with current practice. In selected cases with cytological results falling into category III (according to clinical data and cytopathologists' opinions), direct lobectomy seems to be justified.

[Molecular diagnostics of lung cancer]. / A tüdorák molekuláris diagnosztikája.

Development of the target therapies of lung cancer was a rapid process which fundamentally changed the pathological diagnosis as well. Furthermore, molecular pathology became essential part of the routine diagnostics of lung cancer. These changes generated several practical problems and in underdeveloped countries or in those with reimbursement problems have been combined with further challenges. The central and eastern region of Europe are characterized by similar problems in this respect which promoted the foundation of NSCLC Working Group to provide up to date protocols or guidelines. This present paper is a summary of the molecular pathology and target therapy guidelines written with the notion that it has to be upgraded continuously according to the development of the field.

Primary cilia in gastrointestinal stromal tumors.

The primary cilium is a solitary, sensory, non-motile microtubule-based structure that arises from the centrosome and is projected from the surface of most human cells. The objective of the current pilot study was to conduct an investigation of presence and frequency of cilia in gastrointestinal stromal tumors (GIST).The presence of primary cilia in GIST was evaluated in 9 patients, including 8 primary tumors and 1 liver metastasis. In 2 patients the presence of primary cilia was evaluated not only in the primary tumor, but also in recurrence: in 1 patient in recurrence without previous treatment with imatinib and in 1 patient in recurrence after treatment with imatinib. The primary cilia of GIST cells were immunofluorescently stained with primary monoclonal anti-acetylated tubulin alpha antibody and cell nuclei with DAPI.We observed 9985 nuclei of cells of GISTs and 425 primary cilia in total. The median of frequency of primary cilia in cells of GISTs in all examined samples was 4.26%, in primary tumors was 4.32% and in metastases was 3.64%, respectively. This pilot study provides the evidence of the presence of primary cilia in GISTs in different organs. Primary cilia were identified in all examined cases of GIST, including primary tumors, metastases and recurrent lesions without and with previous treatment with imatinib.

[Influence of preoperative chemoradiotherapy on changes of epidermal growth factor receptor expression in patients treated by preoperative chemoradiotherapy for local advanced rectal carcinoma]. / Vliv predoperacní chemoradioterapie na zmenu exprese receptoru pro epidermální rustový faktor u pacientu lécených predoperacní chemoradioterapií pro lokálne pokrocilý karcinom rekta.

AIM: The aim of this retrospective study was to determine the prognostic impact of expression of epidermal growth factor receptor (EGFR) changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal adenocarcinoma. MATERIAL AND METHODS: One hundred and three patients with locally advanced rectal adenocarcinoma of stage II and III were evaluated. All patients were administered the total dose of 44 --  50.4 Gy. Concomitantly, the patients received capecitabine in the dose 825 mg/ m² in two daily oral administrations or 5- fluorouracil in the dose 200 mg/ m² in continuous infusion. Surgery was indicated at intervals of 4-8 weeks from chemoradiotherapy completion. EGFR expression in the pretreatment biopsies and in resected specimens was assessed with immunohistochemistry. RESULTS: All of 103 patients received radiotherapy without interruption up to the total planned dose. Downstaging was described in 64 patients. Six patients had complete pathologic remission. Recurrence occurred in 49 patients. Local recurrence was found in 22 patients, generalization of disease was reported in 27 patients. A total of 51 patients died. Increased EGFR expression was found in 26 patients. The statistically significantly shorter overall survival (p < 0.001) and disease-free survival (p < 0.001) was found in patients with increased expression of EGFR compared with patients where no increase in the expression of EGFR was observed during neoadjuvant chemoradiotherapy. CONCLUSIONS: The overexpression of EGFR during neoadjuvant chemoradiotherapy for locally advanced rectal adenocarcinoma is associated with significant shorter overall survival and disease-free survival.

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.

[Evaluation of safe resection margins in rectal carcinoma]. / Problematika stanovení bezpecných resekcních okraju u karcinomu rekta.

The fact that surgically well performed total mesorectal excision with negative circumferential resection margin represents one of the most important prognostic factors in colorectal carcinoma is already well known. These parameters significantly affect the incidence of local tumour recurrence as well as distant metastasis, and are thus related to the duration of patient survival. The surgeons task is to perform mesorectal excision as completely as possible, i.e., to remove the rectum with an intact cylinder of mesorectal fat. The approach of the pathologist to evaluation of total mesorectal excision specimens differs greatly from that of resection specimens from other parts of the large bowel. Besides evaluation of the usual parameters for colon cancer staging, it is essential to assess certain additional factors specific to rectal carcinomas, namely tumour distance from circumferential (radial) resection margins and the quality of the mesorectal excision. In order to accurately evaluate these parameters, knowledge of a wide range of clinical data is indispensable (results of preoperative imaging, intraoperative findings). For objective evaluation of these parameters it is necessary to introduce standardized procedures for resection specimen processing and macro and microscopic examination. This approach is based mainly on standardized macroscopic photo-documentation of the integrity of the mesorectal surface. Parallel transverse sections of the resection specimens are made with targeted tissue sampling for histological examination. It is essential to have close cooperation between surgeons and pathologists within a multidisciplinary team enabling mutual feedback.

Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer.

BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.

Predictive biomarkers in breast cancer: their value in neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NCT) of breast cancer enabled improved outcomes especially in patients with advanced and inflammatory diseases. Biological heterogeneity of these tumors, however, requires better molecular characterization of the malignant tissue with consequent individualization in the selection of appropriate agents. To date, numerous molecular markers have been identified, and some of them (e.g., measurement of hormonal or growth factors receptors) are already routinely used for breast cancer classification before NCT. In the present article, we summarize current knowledge about established as well as promising biomarkers which have demonstrated prognostic or predictive value in NCT of breast cancer.

[Prognostic significance of changes of tumor epidermal growth factor receptor expression after neoadjuvant chemoradiation in patients with rectal adenocarcinoma].

PURPOSE: The aim of the present study was to examine the effect of neoadjuvant chemoradiation on tumor epidermal growth factor receptor (EGFR) expression in patients with locally advanced rectal adenocarcinoma. PATIENTS AND METHODS: A total of 53 patients with rectal adenocarcinoma (clinical stages II and III) were studied. Neoadjuvant treatment consisted of 50.4 Gy/28 fractions external radiation with concomitant continuous 5-fluorouracil. Surgical resection was performed 4-6 weeks after the chemoradiation. EGFR expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry. RESULTS: Patients with an increase of EGFR expression during chemoradiation had significantly shorter disease-free survival (DFS; p = 0.003) and overall survival (OS; p = 0.005) compared to patients with either no change or decrease in EGFR expression. The 5-year DFS in patients with increased EGFR expression was only 29% compared to 61% in patients without an increase of EGFR expression. Similarly, the 5-year OS of the patients with increased EGFR expression was 29% compared to 66% in patients without an increase of EGFR expression. All recurrences in patients who had an increase of EGFR expression occurred within the first 2 years after the treatment. The increase in EGFR expression was the only significant predictor of DFS (p = 0.007) and OS (p = 0.04) using multivariate Cox regression analysis. CONCLUSION: An increase of EGFR expression during chemoradiation may be associated with significantly shorter DFS and OS. The increase of EGFR could identify a population of patients in whom the effect of the treatment with anti-EGFR therapy should be studied.

Biologic importance and prognostic significance of selected clinicopathological parameters in patients with oral and oropharyngeal squamous cell carcinoma, with emphasis on smoking, protein p16(INK4a) expression, and HPV status.

The aim of this study is to evaluate the biologic importance and prognostic significance of selected clinicopathological parameters in patients with oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinoma, with emphasis on smoking, protein p16(INK4a) (p16) expression, and human papillomavirus (HPV) status.The study sample consisted of 48 patients with OSCC and 44 patients with OPSCC. Half of the patients were nonsmokers and the other half were gender-, age- and tumor localization-matched smokers. p16 expression was detected in 17/48 (35 %) OSCCs and in 36/44 (82 %) OPSCCs and HPV DNA was present in 7/48 (15 %) OSCCs and in 35/44 (80 %) OPSCCs. The sensitivity and specificity of p16 expression for HPV DNA presence were 0.74 and 0.88, respectively. The OPSCCs were more frequently basaloid (p < 0.001) while the OSCCs were more frequently conventional (p < 0.000001). The OSCCs were more likely to recur locally and to be the cause of death (p = 0.009 in both parameters).The HPV-positive tumors were more frequently localized in oropharynx, were basaloid SCCs and were p16- and HPV-positive (p < 0.000001 in all 4 parameters). The HPV-negative tumors were more frequently localized in oral cavity (p < 0.000001), more frequently asociated with local, regional and locoregional recurence (p = 0.011, p = 0.019 and p = 0.030, respectively) and with tumor-related death (p = 0.003). There was no significant difference with regard to smoking history (p > 0.05). The survival of patients with HPV-positive tumors was significantly longer (median 112 months; 95% CI 54 - 112 months) than that of patients with HPV-negative tumors (median 17 months; 95% CI 12 - 39 months) (p < 0.001). The HPV status of OSCC/OPSCC is an important biological and prognostic parameter and should be examined in all cases, using PCR or immunohistochemical detection of surrogate marker p16. Smoking itself does not seem to be an important prognostic factor.

Cellular cohesiveness in benign and malignant thyroid follicular tumours varies significantly, but the difference is not useful in diagnosis of individual cases.

INTRODUCTION: The aim of our study was to search for new, readily available and statistically reliable cytological markers for differentiating benign and malignant follicular thyroid neoplasms pre-operatively. METHODS: Cohesiveness of tumour cells in cytology slides from a series of 58 follicular tumours diagnosed between 1998 and 2004 inclusive was studied, including 48 follicular adenomas, and eight minimally invasive and two widely invasive follicular carcinomas. Photomicrographs of the cytology slides were taken and the digital images were analysed using computer image analysis software. We evaluated the relative proportions of cells arranged in groups of various sizes. The cohesiveness of the cells in cytological smears was then correlated with the immunohistochemical expression of E-cadherin in corresponding histological slides. RESULTS: Cases from 15 men (26%) and 43 women (74%) with a mean age of 50 years (range, 19-79) were analysed. In follicular adenomas and carcinomas, respectively, isolated cells were seen in 16.8% and 24.7% (P = 0.028), groups of two to five cells in 9.7% and 11.5% (P = 0.145) and groups of more than five cells in 73.5% and 63.8% (P = 0.041). The mean cell count in groups with more than five cells was 46.5 and 27.0 in adenomas and carcinomas, respectively (P < 0.001). Cell cohesiveness, either as percentage of cells in groups of more than five (R(2) = 0.026) or as mean cell count per group of more than five (R(2) = 0.005), was not found to be dependent on the expression of E-cadherin. Using a threshold of 13% isolated tumour cells in cytological smears, follicular adenomas and carcinomas could be distinguished with 90% sensitivity and 41% specificity. CONCLUSIONS: Although we demonstrated a statistically significant difference in cell cohesion between follicular adenomas and carcinomas, these could not be distinguished in the clinical setting by evaluation of the percentage of isolated cells in cytological smears because the specificity was too low. The absence of correlation of cellular cohesiveness with E-cadherin expression indicates that other factors are probably responsible for the loss of cohesiveness observed in follicular thyroid malignancy.

Low expression of NQO1 predicts pathological complete response to neoadjuvant chemotherapy in breast cancer patients treated with TAC regimen.

The aim of this study was to evaluate preoperative tumour expression of NAD(P)H:quinone oxidoreductase 1 (NQO1) along with other biological markers as potential predictors of pathological complete response (pCR) to neoadjuvant docetaxel, doxorubicin, and cyclophosphamide-containing (TAC) chemotherapy in patients with primary breast cancer. Sixty-one patients who received neoadjuvant chemotherapy (NCT) with TAC regimen were enrolled in this prospective study. The pre- and post- NCT expression of oestrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 1 and 2 (EGFR and HER2), NQO1, Ki-67 proliferation index, multidrug resistance protein 1 (MDR1), p53 and BCL2 were evaluated by immunohistochemistry. The pCR was reached in 14 patients (23 % of the study group). Multivariate analysis demonstrated that patients with ER-, PR-, NQO1- negative, and Ki-67-positive tumours had a significantly higher chance to achieve pCR. Within the biological subtypes, the highest pCR rate (50 %) was seen in triple-negative (i.e. ER-, PR-, HER2-) tumours. Post-operative evaluation showed that in comparison to pre-operative tissue samples, NQO1 expression was significantly increased, while Ki-67 and HER2 decreased, in the residual tissue after NCT. In conclusion, the present data suggests that NQO1 expression may be a novel diagnostic biomarker for the prediction of positive response to NCT in patients with breast cancer.

[Primary cilia of cells of cardiovascular apparatus]. / Primární rasinky bunek kardiovaskulárního aparátu.

The primary cilium is a mechanosensory, solitary, non-motile microtubule-based structure that in the quiescent phase of the cell cycle projects from the surface of the majority of human cells, including embryonal, stem and mesenchymal cells, fibroblasts, myoblasts, cardiomyocytes, vascular smooth muscle and endothelial cells. Primary cilia are in increased frequency also present on the surface of endothelial cells in atherosclerotic predilection sites, lipoid streaks and dots and atheromatous plaques. The primary cilium is formed from the mother centriole. Primary cilia are currently studied in mechanobiology of cardiovascular apparatus and their role in cell migration, cell cycle control and atherogenesis. The aim of this paper is to provide a review of the current knowledge on the primary cilia of cells of cardiovascular apparatus.