Tamás Székely

Expression of Claudins and Their Prognostic Significance in Noninvasive Urothelial Neoplasms of the Human Urinary Bladder

The members of the claudin family are major integral transmembrane protein constituents of tight junctions. Normal and neoplastic tissues can be characterized by unique qualitative and quantitative distribution of claudin subtypes, which may be related to clinicopathological features. Differential diagnosis and prognosis of nonmuscle invasive tumor entities of urinary bladder epithelium are often challenging. The aim was to investigate the expression profile of claudins in inverted urothelial papillomas (IUPs), urothelial papillomas (UPs), papillary urothelial neoplasms of low malignant potential (PUNLMPs), and intraepithelial (Ta), low-grade urothelial cell carcinomas (LG-UCCs) in order to reveal potential prognostic and differential diagnostic values of certain claudins. Claudin-1, -2, -4, and -7 protein expressions detected by immunohistochemistry and clinical data were analyzed in 15 IUPs, 20 UPs, 20 PUNLMPs, and 20 LG-UCCs. UPs, PUNLMPs, and LG-UCCs showed significantly decreased claudin-1 expression in comparison to IUPs. LG-UCCs expressing claudin-4 over the median were associated with significantly shorter recurrence-free survival. PUNLMPs expressing claudin-1 over the median revealed significantly longer recurrence-free survival. High claudin-1 protein expression might help to differentiate IUP from UPs, PUNLMPs, and LG-UCCs. High claudin-4 expression may determine an unfavorable clinical course of LG-UCCs, while high claudin-1 expression in PUNLMP was associated with markedly better clinical outcome.

E-Cadherin Expression in Transitional Cell Carcinomas

The authors analyzed the expression of E-cadherin, one of the most important cell adhesion molecules, on paraffin sections of tumors of bladder cancer patients. The aim of the study was to see whether there is any association between E-cadherin expression and tumor grade, stage, age and gender of the patients, number of recurrences, or overall survival. The samples were examined in 51 primary bladder transitional cell carcinomas (TCC) of 50 patients, resected by transurethral resection (TUR) between January 1, 1996 and January 1, 1997. Immunoreactions were performed with monoclonal anti-human E-cadherin antibody. Forty of the fifty patients could be clinically followed. The analysis of the results on these forty patients was performed by contingency analysis and significance was assessed by Ξ2 test. No significant association between E-cadherin expression and tumor grade, stage, age or gender of the patients, the number of recurrences, or overall survival could be seen. (Pathology Oncology Research Vol 12, No 2, 73–77)

The coverage of cervical screening in Hungary

UNLABELLED The purpose of this study is to calculate the proportion of women having cytological examination (Pap smear) of cervix either within or outside of the Hungarian organized cervical cancer screening programme. METHODS The data derive from the financial database of the National Health Insurance Fund Administration (OEP) of Hungary covering the period of 2000-2005. The period 2000-2002 was considered as a reference period of opportunistic screening, while 2003-2005 was the first screening circle of organized screening. RESULTS Between 2000-2002 1 667 618 women underwent cytological examination of Pap smear, and it increased to 1 749 498 women between 2003-2005. In the age-group 25-64 years, the annual coverage varied between 22.0-23.3% in 2000-2002, and it increased to 23.4-24.3% between 2003-2005. In the target population the 3-years-coverage increased from 48.9% in 2000-2002 to 52.6% in 2003-2005 (+3.7%). CONCLUSIONS The organized screening programme managed to increase moderately the coverage of target population. In order to realize the mortality decline due to cervical cancer, participation rate must be increased.

LAPTM4B gene copy number gain is associated with inferior response to anthracycline-based chemotherapy in hormone receptor negative breast carcinomas

PurposeTo determine the associations between lysosomal-associated transmembrane protein 4b (LAPTM4B) gene copy number and response to different chemotherapy regimens in hormone receptor negative (HR-) primary breast carcinomas.Patients and methodsTwo cohorts were analyzed: (1) 69 core biopsies from HR-breast carcinomas treated with neoadjuvant chemotherapy (anthracycline based in 72.5% of patients and non-anthracycline based in 27.5% of patients). (2) Tissue microarray (TMA) of 74 HR-breast carcinomas treated with adjuvant therapy (77.0% of the patients received anthracycline, 17.6% of the patients non-anthracycline-based therapy, and in 5.4% of the cases, no treatment data are available). Interphase FISH technique was applied on pretreatment core biopsies (cohort I) and on TMAs (cohort II) using custom-made dual-labelled FISH probes (LAPTM4B/CEN8q FISH probe Abnova Corp.).ResultsIn the neoadjuvant cohort in the anthracycline-treated group, we observed a significant difference (p = 0.029) of average LAPTM4B copy number between the non-responder and pathological complete responder groups (4.1 ± 1.1 vs. 2.6 ± 0.1). In the adjuvant setting, the anthracycline-treated group of metastatic breast carcinomas was characterized by higher LAPTM4B copy number comparing to the non-metastatic ones (p = 0.046). In contrast, in the non-anthracycline-treated group of patients, we did not find any LAPTM4B gene copy number differences between responder vs. non-responder groups or between metastatic vs. non-metastatic groups.ConclusionOur results confirm the possible role of the LAPTM4B gene in anthracycline resistance in HR− breast cancer. Analyzing LAPTM4B copy number pattern may support future treatment decision.

PREDICTIVE VALUE OF SOMATIC MUTATIONS FOR THE DEVELOPMENT OF MALIGNANCY IN THYROID NODULES BY CYTOPATHOLOGY

OBJECTIVE The purpose of our prospective longitudinal study was to evaluate the predictive efficacy of genetic testing for malignancies in fine-needle aspiration biopsy samples that are cytologically benign at the time of biopsy. METHODS A total of 779 aspirated cytological samples collected from thyroid nodules of 626 patients were included in a 3-year follow-up study. Consecutive patients with cytologically benign thyroid nodules by the Bethesda System for Reporting Thyroid Cytopathology were enrolled in the study. At enrollment, somatic 1-point nucleotide polymorphisms of BRAF and RAS family genes were tested by melting-point analysis, while RET/PTC and PAX8/PPAR-gamma rearrangements were examined by real-time polymerase chain reaction. The genetic test was considered to be positive if a somatic mutation was found. Malignant cytopathologic diagnoses were confirmed by histopathology. RESULTS In samples collected from 779 thyroid nodules, there were 39 BRAF, 33 RAS mutations, and 1 RET/PTC rearrangements found at the beginning of the study. No PAX8/PPAR-gamma rearrangement was identified. There were 52 malignant thyroid tumors removed during follow-up, out of which 24 contained a somatic mutation. The specificity of the presence of somatic mutations for malignancies was as high as 93.3%, and sensitivity was 46.2%. The negative predictive value of genetic testing reached 96.0%. CONCLUSION Our results show that our set of genetic tests can predict the appearance of malignancy in benign thyroid nodules (at the beginning of follow-up) with high specificity and strong negative predictive value. ABBREVIATIONS BRAF = v-raf murine sarcoma viral oncogene homolog B1 FLUS = follicular lesion of undetermined significance FNAB = fine-needle aspiration biopsy FTC = follicular thyroid carcinoma HRAS = homologous to the oncogene from the Harvey rat sarcoma virus KRAS = homologous to the oncogene from the Kirsten rat sarcoma virus NRAS = first isolated from a human neuroblastoma/neuroblastoma RAS = viral oncogene homolog PAX8 = paired box 8 PCR = polymerase chain reaction PPAR-gamma = peroxisome proliferator-activated receptor gamma PTC = papillary thyroid carcinoma RAS = rat sarcoma RET = rearranged during transfection tyrosine-kinase proto-oncogene SM = somatic mutation SNP = single-nucleotide polymorphism.

A méhnyakszûrés részvételi mutatói Magyarországon

A dolgozat celja annak meghatarozasa, hogy Magyarorszagon a nok hany szazaleka vesz reszt nogyogyaszati citologiai vizsgalaton (lefedettseg), akar a szervezett szurovizsgalat kereteben, akar az egyeb nogyogyaszati vizsgalatok soran. Adatok es modszerek: Az elemzes az Orszagos Egeszsegbiztositasi Penztar (OEP) rutinszeruen gyujtott finanszirozasi adatokat tartalmazo adatbazisara epul. A vizsgalatban a 2000 es 2002 kozotti 3 eves periodus volt az opportunisztikus szures referencia-idoszaka, mig a 2003 es 2005 kozotti 3 ev a szervezett szures elso szuresi ciklusa. Eredmenyek: Mig a 2000 es 2002 kozotti 3 evben 1 667 618 nonel vegeztek citologiai vizsgalatot, addig ez a szam 2003 es 2005 kozott 1 749 498 fore emelkedett. A 25–64 ev kozotti noi korosztalyban 2000 es 2002 kozott az 1 eves lefedettseg 22,0–23,3% kozott valtozott, ami 2003 es 2005 kozott 23,4–24,3%-ra emelkedett. A 2000 es 2002 kozotti 3 eves lefedettseg pedig 48,9%-rol 2003 es 2005 kozott 52,6%-ra emelkedett a szervezett szuressel erintett celpopulacioban (+ 3,7%). Kovetkeztetes: A szervezett szures kismertekben novelte a citologiai vizsgalaton reszt vevo nok szamat. Ahhoz azonban, hogy erdemi mortalitascsokkenest eredmenyezzen a program, a reszveteli mutatokat novelni szukseges. Kulcsszavak: mehnyakrak, mehnyakszures, lakossagi szures, atszurtseg, Magyarorszag The coverage of cervical screening in Hungary. The purpose of this study is to calculate the proportion of women having cytological examination (Pap smear) of cervix either within or outside of the Hungarian organized cervical cancer screening programme. Methods: The data derive from the financial database of the National Health Insurance Fund Administration (OEP) of Hungary covering the period of 2000–2005. The period 2000–2002 was considered as a reference period of opportunistic screening, while 2003–2005 was the first screening circle of organized screening. Results: Between 2000–2002 1 667 618 women underwent cytological examination of Pap smear, and it increased to 1 749 498 women between 2003–2005. In the age-group 25–64 years, the annual coverage varied between 22.0–23.3% in 2000–2002, and it increased to 23.4–24.3% between 2003–2005. In the target population the 3-years-coverage increased from 48.9% in 2000–2002 to 52.6% in 2003–2005 (+ 3.7%). Conclusions: The organized screening programme managed to increase moderately the coverage of target population. In order to realize the mortality decline due to cervical cancer, participation rate must be increased.