15 research outputs found
HOST AND BACTERIAL FACTORS IN PATHOGENESIS OF LISTERIOSIS
SAŽETAK
Listerioza jest zoonoza do koje u veÄem broju sluÄajeva dolazi nakon konzumacije zagaÄenih namirnica. U zdravih odraslih osoba infekcija bakterijom Listeria monocytogenes posljeduje prolaznom, asimptomatskom kolonizacijom crijeva, ili slikom neinvazivna febrilnoga
gastroenteritisa. Infekcija fetusa, novoroÄenÄeta, ili imunokompromitirane osobe, može posljedovati razvojem invazivne infekcije praÄene visokim postotkom smrtnosti. Zbog svojstva unutarstaniÄnoga parazitiranja, bakterija Listeria monocytogenes dugi se niz godina koristi kao
oruÄe za prouÄavanje staniÄne biologije i mehanizama staniÄne imunosti.ABSTRACT
Listeriosis is a zoonosis usually transmitted through contaminated food or vertically from mother to foetus. In an immunocompetent, adult person the infection results in transitory asymptomatic gastrointestinal colonization or febrile, non-invasive gastroenteritis. The infection of the foetus, newborn or immunocompromised person can result in a serious invasive disease with high mortality rate. As a facultative intracellular pathogen, Listeria monocytogenes is widely used as model for studying cellular biology and mechanisms of cellular immunity
Evaluation of the HPV L1 Capsid Protein in Prognosis of Mild and Moderate Dysplasia of the Cervix Uteri
Cervical intraepithelial neoplasia (CIN) can be detected in the cytologic smears years before invasive squamous cancer arises, but no reproducible morphologic criteria exist to predict behavior of cervical lesions. The possibility of predicting the clinical course of cervical lesions could be of high value in clinical practice and some women will spare of unnecessary treatment. HPV L1 capsid protein represents about 90% of the total protein on the surface of the virus and can be detected in mild to moderate dysplasia and rarely in severe dysplasia. The purpose of the study was to evaluate the use of immunodetection of HPV L1 protein on archival Pap smears with findings of mild and moderate dysplasia in predicting its clinical course. Immunochemical analyses with L1 antibody revealed positively stained nuclei of squamous epithelial cells in 56 of 114 smears (49.1%). The staining results were correlated with follow-up smears or with histologic verification. Regression (negativisation of the Pap smear for 24 months or longer) was noticed in 31 of 56 (55.4%) L1-positive cases and in 20 of 58 (34.5%) L1-negative cases. Persistent disease occured in 13 (23.2%) L1-positive cases and in 14 (24.1%) L1-negative cases. Progressive disease occured in 12 (21.4%) L1-positive cases and in 24 (41.4%) L1-negative cases. The difference in the clinical course between the L1-positive and L1-negative patients was statistically significant (p=0.025). Also, the difference in the clinical course of the L1-negative staining in the under-30 and over-30 years age group was statistically significant (p=0.04). For conclusion, our data confirm that immunostaining for HPV L1 capsid protein could offer prognostic information about mild and moderate intraepithelial cervical squamous lesions
Evaluation of the HPV L1 Capsid Protein in Prognosis of Mild and Moderate Dysplasia of the Cervix Uteri
Cervical intraepithelial neoplasia (CIN) can be detected in the cytologic smears years before invasive squamous cancer arises, but no reproducible morphologic criteria exist to predict behavior of cervical lesions. The possibility of predicting the clinical course of cervical lesions could be of high value in clinical practice and some women will spare of unnecessary treatment. HPV L1 capsid protein represents about 90% of the total protein on the surface of the virus and can be detected in mild to moderate dysplasia and rarely in severe dysplasia. The purpose of the study was to evaluate the use of immunodetection of HPV L1 protein on archival Pap smears with findings of mild and moderate dysplasia in predicting its clinical course. Immunochemical analyses with L1 antibody revealed positively stained nuclei of squamous epithelial cells in 56 of 114 smears (49.1%). The staining results were correlated with follow-up smears or with histologic verification. Regression (negativisation of the Pap smear for 24 months or longer) was noticed in 31 of 56 (55.4%) L1-positive cases and in 20 of 58 (34.5%) L1-negative cases. Persistent disease occured in 13 (23.2%) L1-positive cases and in 14 (24.1%) L1-negative cases. Progressive disease occured in 12 (21.4%) L1-positive cases and in 24 (41.4%) L1-negative cases. The difference in the clinical course between the L1-positive and L1-negative patients was statistically significant (p=0.025). Also, the difference in the clinical course of the L1-negative staining in the under-30 and over-30 years age group was statistically significant (p=0.04). For conclusion, our data confirm that immunostaining for HPV L1 capsid protein could offer prognostic information about mild and moderate intraepithelial cervical squamous lesions
Villoglandular Papillary Adenocarcinoma of the Uterine Cervix with Aggressive Clinical Course ā A Case Report
Villoglandular papillary adenocarcinoma (VGA) of cervix is an uncommon but well recognized histologic subtype of cervical adenocarcinoma which usually affects young women. Based on the favorable outcomes reported in most previous cases the tumor is generally considered to have an indolent clinical course with excellent prognosis. We present a case of a 22-year-old woman admitted at our Department for glandular abnormality on cervical smear and episodes of vaginal discharge. In the Pap smear, the cytological features were suspicious but not diagnostic of adenocarcinoma, therefore reported as atypical glandular cells (AGC). Histological examination confirmed VGA associated with lymphovascular space invasion. The patient underwent radical operative procedure. Intraoperative cytologic examination detected pelvic lymph nodes metastasis. The patient was confirmed to be in an advanced stage ā III B (FIGO). During a two years follow-up period a rapid dissemination of the tumor occurred and resulted with a fatal outcome. Although VGA has been reported to have a favorable prognosis, several cases with lymph node involvement have already been described. Cervical smears examination would be helpful for an early diagnosis of VGA, however the cytologic recognition is often difficult. Further investigation of the pathogenesis, diagnosis and therapy of the tumor is needed
Villoglandular Papillary Adenocarcinoma of the Uterine Cervix with Aggressive Clinical Course ā A Case Report
Villoglandular papillary adenocarcinoma (VGA) of cervix is an uncommon but well recognized histologic subtype of cervical adenocarcinoma which usually affects young women. Based on the favorable outcomes reported in most previous cases the tumor is generally considered to have an indolent clinical course with excellent prognosis. We present a case of a 22-year-old woman admitted at our Department for glandular abnormality on cervical smear and episodes of vaginal discharge. In the Pap smear, the cytological features were suspicious but not diagnostic of adenocarcinoma, therefore reported as atypical glandular cells (AGC). Histological examination confirmed VGA associated with lymphovascular space invasion. The patient underwent radical operative procedure. Intraoperative cytologic examination detected pelvic lymph nodes metastasis. The patient was confirmed to be in an advanced stage ā III B (FIGO). During a two years follow-up period a rapid dissemination of the tumor occurred and resulted with a fatal outcome. Although VGA has been reported to have a favorable prognosis, several cases with lymph node involvement have already been described. Cervical smears examination would be helpful for an early diagnosis of VGA, however the cytologic recognition is often difficult. Further investigation of the pathogenesis, diagnosis and therapy of the tumor is needed
Cervical cytology (Pap test) ā terminology and importance in screening for cervical cancer
. Papa-test je najbolji morfoloÅ”ki test probira za rak koji pomoÄu analize citologije vrata maternice otkriva predstadije i rane stadije raka vrata maternice. U Hrvatskoj se koristi u okviru oportunistiÄkog probira, a od 1. 12. 2012. u organiziranom nacionalnom probiru. U svrhu klasifikacije i standardizacije citoloÅ”kih nalaza vrata maternice u cijeloj Hrvatskoj koristi se modifikacija Bethesda klasifikacije. Obrazac sadrži kliniÄke podatke o pacijentici koje ispunjava ginekolog i citoloÅ”ki nalaz koji na osnovi analize Papa-testa pod svjetlosnim mikroskopom izdaje kliniÄki citolog. U ovom preglednom radu opisuju se citomorfoloÅ”ke osobine abnormalnih ploÄastih i cilindriÄnih stanica vrata maternice te njihov kliniÄki znaÄaj. Zbog dokazane povezanosti humanog papiloma-virusa (HPV) s rakom vrata maternice sve ÄeÅ”Äe se detekcija visokoriziÄnog HPV-a uvodi u probir za rak vrata maternice. U novije vrijeme metode temeljene na bioloÅ”kim biljezima primjenjuju se na citoloÅ”kim uzorcima u svrhu poboljÅ”anja osjetljivosti i specifiÄnosti citologije u otkrivanju lezija visokog stupnjaThe Pap test is considered to be the best morphological screening test for cancer which reveals precancerous lesions and early stages of cervical cancer by analyzing cervical cytology. In Croatia, it is used in the context of opportunistic screening and since December 1, 2012 it has been used within an organized national screening programme. In order to classify and unify the terminology in cervical cytology reporting throughout Croatia a modification of the Bethesda classification is used. The form contains clinical data on the patient which is fulfilled by the gynecologist and the cytological report based on light microscope analysis of Pap smears which is made by the cytopathologist. In this article we will describe the cytological characteristics of abnormal squamous and glandular cells as well as their clinical significance. Since the connection between human papillomavirus (HPV) and cervical cancer has been clearly confirmed the detection of high-risk HPV is increasingly implemented in cervical cancer screening. More recently, in order to improve the sensitivity and specificity of cytology methods in detecting high-grade lesions, biological markers are applied on cytological specimens of the cervi
The role of cytology in preoperative assessment od primary fallopian tube carcinoma: case report
Cilj: Prikazati sluÄaj pacijentice s primarnim seroznim karcinomom jajovoda, opisati dijagnostiÄki postupak te analizirati ulogu citoloÅ”ke dijagnostike u detekciji ovog tipa tumora. Prikaz sluÄaja: PedesetogodiÅ”nja pacijentica prethodno je obraÄivana u drugoj ustanovi zbog bolova u trbuhu i radioloÅ”ki dokazanih uveÄanih supraklavikularnih, aortokavalnih i ilijaÄnih limfnih Ävorova. Nakon uÄinjene laparoskopske ekstirpacije limfnih Ävorova zbog sumnje na limfoproliferativnu bolest, patohistoloÅ”kom i imunohistokemijskom analizom utvrÄeno je da se radi o metastatskom adenokarcinomu, vjerojatno podrijetla iz ginekoloÅ”kog sustava ili dojke. RadioloÅ”kom obradom dojki nisu pronaÄene promjene suspektne na malignitet. PET/CT analizom (pozitronska emisijska tomografija/kompjutorizirana tomografija) uoÄeno je pojaÄano nakupljanje radiofarmaka u predjelu vrata i tijela maternice. U preoperativnoj obradi uÄinjena je citoloÅ”ka punkcija uveÄanog supraklavikularnog limfnog Ävora te je imunocitokemijskom analizom utvrÄeno da se radi o metastatskom seroznom adenokarcinomu. U Papa-testu pronaÄene su maligne stanice jednake morfologije, bez tumorske dijateze, Å”to je upuÄivalo na ekstrauterini adenokarcinom, a sugerirano je podrijetlo jajnika ili jajovoda. UÄinjena je eksplorativna kiretaža, ali je patohistoloÅ”ki nalaz bio uredan. Pacijentica je predviÄena za histerektomiju s obostranom adnekstektomijom. Tijekom operativnog zahvata uoÄeno je proÅ”irenje desnog jajovoda tumorskim tkivom koje je probijalo stijenku jajovoda. UÄinjena je lavaža peritonealne Å”upljine u kojoj su pronaÄene maligne stanice adenokarcinoma. PatohistoloÅ”ka analiza potvrdila je da se radi o primarnom seroznom karcinomu jajovoda s metastazama u jajnicima. ZakljuÄak: ZahvaljujuÄi brzini i preciznosti primijenjenih citodijagnostiÄkih pretraga dijagnostiÄko-terapijski postupak pravilno je usmjeren i pravovremeno proveden. Prikazani sluÄaj potvrÄuje da citoloÅ”ka analiza može pridonijeti dijagnostici tumora s neuobiÄajenom kliniÄkom prezentacijom ili tumora nejasnog podrijetla.Aim: To report a case of a patient with primary serous carcinoma of the fallopian tube, describe the diagnostic pathway and analyze the role of cytology in the detection of this tumor type. Case report: A 50-year-old patient was previously treated in another hospital for abdominal pain and radiologically confirmed enlargement of supraclavicular, aortocaval and iliac lymph nodes. A lymphoproliferative disorder was suspected and laparoscopic lymph node excision was performed. Histopathological and immunohistochemical analysis revealed a metastatic adenocarcinoma probably of gynecologic or breast cancer origin. Radiographic examination of the breast did not confirm any lesion suspicious for malignancy. Positron emission tomography/computed tomography observed increased radiotracer uptake involving the uterine cervix and corpus. Preoperative fine-needle aspiration cytology and immunocytochemical analysis of an enlarged supraclavicular lymph node was done and metastatic serous adenocarcinoma was confirmed. In the Pap smears malignant cells of equal morphology were found without tumor diathesis indicating an extra-uterine adenocarcinoma. It was suggested to consider a tumor of ovarian or fallopian tube origin. A total hysterectomy with bilateral salpingo-oophorectomy was performed. During surgery an enlargement of the was observed due to tumor growth extending through the tubal wall. The presence of malignant adenocarcinoma cells was found in the peritoneal washing. Histopathological analysis confirmed a primary serous carcinoma of the fallopian tubes with metastatic spread to the ovaries. Conclusion: Applying fast and precise cytology and immunocytochemistry techniques a correct diagnostic and therapeutic approach can be performed and implemented on time. The present case confirms that cytology is a wellestablished and widely accepted method for diagnosing tumors with unusual clinical presentation or unknown origin
EXPRESSION OF E-CADHERIN AND Ī²-CATENIN IN EPITHELIAL-MESENCHYMAL TRANSITION AND THEIR PROGNOSTIC VALUE IN ENDOMETRIAL CARCINOMA
Cilj istraživanja: KljuÄni mehanizam odgovoran za progresiju karcinoma endometrija (KE) je aktivacija epitelno-mezenhimalne tranzicije (EMT), procesa kojim tumorske stanice stjeÄu mezenhimalni fenotip. Glavnim obilježjem EMT smatra se gubitak adhezijske molekule E-kaderina, nuklearna akumulacija Ī²-katenina i stjecanje N-kaderina. Takve tumorske stanice ulaze u kaskadu invazija-metastaziranje, a u metastazama prolaze obrnuti proces mezenhimalno-epitelne tranzicije (MET). Na histoloÅ”kom nivou malo je podataka o znaÄaju aberantnog izražaja ovih proteina u KE.
Ispitanici i metode: U istraživanje je ukljuÄeno 86 bolesnica. Za imunohistokemijsku analizu napravljeni su tkivni rezovi primarnih tumora KE i njihovih metastaza te odreÄen postotak i jaÄina obojanosti tumorskih stanica na E-kaderin, Ī²-katenin i N-kaderin u centru tumora (CT), na invazivnoj fronti (IF), u limfovaskularnom prostoru (LVP) te u pripadajuÄim metastazama.
Rezultati: UtvrÄen je znaÄajan pad izražaja E-kaderina od CT prema IF (p< 0.0001) uz istovremeno pojaÄan izražaj N-kaderina (p=0.005) Å”to govori u prilog nastupu procesa EMT. UoÄeno je smanjenje membranskog Ī²-katenina od CT prema IF i LVP, dok nuklearni izražaj Ī²-katenina nije potvrÄen kao znaÄajni pokazatelj EMT. Usporedbom u odnosu na IF u metastazama je dokazan ponovni izražaj E-kaderina (p=0.049) i gubitak N-kaderina (p=0.008) Å”to govori u prilog aktivaciji MET. Negativni membranski Ī²-katenin na IF povezan je s dubokom invazijom miometrija (p=0.004) i znaÄajno kraÄim preživljenjem bolesnica (p=0.0439).
ZakljuÄak: Rezultati ovog istraživanja doprinijeli su boljem razumijevanju E-kaderina, N-kaderina i Ī²-katenina u procesu EMT i MET u KE. Imunohistokemijska analiza ispitivanih biljega dokazala je da postoji heterogenost u njihovom izražaju unutar tumora i u metastazama te poduprla hipotezu da je IF kljuÄna tumorska regija u kojoj nastupa EMT.Objectives: The key mechanism responsible for the progression of endometrial carcinoma (EC) is the activation of epithelial-mesenchymal transition (EMT) a process which helps epithelial cells to acquire mesenchymal phenotype. One of the hallmarks of EMT is the loss of the adhesion molecule E-cadherin, nuclear accumulation of Ī²-catenin and the acquisition of N-cadherin. Such tumor cells enter the invasion-metastasis cascade; while through the process of mesenchymal-epithelial transition (MET) re-establish their epithelial phenotype at distant sites. Little is known about aberrant expression of these proteins at histological level in EC.
Patients and Methods: The study included 86 patients. For the immunohistochemical analysis tissue samples of primary tumors and their metastases were selected and the expression of E-cadherin, N-cadherin and Ī²-catenin on the basis of percentage of positive tumor cells and staining intensity assessed in the central area (CA) of the tumor, at the invasive front (IF), in lymphovascular spaces (LVS) and metastases.
Results: We found a significantly reduced expression of E-cadherin at the IF when compared to CA (p <0.0001) and a simultaneous higher expression of N-cadherin (p=0.005) indicating the appearance of the EMT process. A less significant reduction of positive membrane Ī²-catenin from CA to IF was observed, while nuclear Ī²-catenin expression was not correlated to EMT. We confirmed a re-expression of E-cadherin in metastases when compared to the IF (p=0.049) and a simultaneous significant loss of N-cadherin (p=0.008) suggesting the activation of MET. Negative membrane Ī²-catenin at the IF was associated with deep myometrial invasion (p=0.004) and significantly shorter patient survival (p=0.0439).
Conclusion: The results of our research have contributed to a better understanding of the role of E-cadherin, N-cadherin and Ī²-catenin in the EMT and MET processes in EC. The immunohistochemical analysis of these markers confirmed that there is great heterogeneity within tumor areas in their expression as well as in metastases and support the hypothesis that the IF is the main tumor region in which EMT occurs
EXPRESSION OF E-CADHERIN AND Ī²-CATENIN IN EPITHELIAL-MESENCHYMAL TRANSITION AND THEIR PROGNOSTIC VALUE IN ENDOMETRIAL CARCINOMA
Cilj istraživanja: KljuÄni mehanizam odgovoran za progresiju karcinoma endometrija (KE) je aktivacija epitelno-mezenhimalne tranzicije (EMT), procesa kojim tumorske stanice stjeÄu mezenhimalni fenotip. Glavnim obilježjem EMT smatra se gubitak adhezijske molekule E-kaderina, nuklearna akumulacija Ī²-katenina i stjecanje N-kaderina. Takve tumorske stanice ulaze u kaskadu invazija-metastaziranje, a u metastazama prolaze obrnuti proces mezenhimalno-epitelne tranzicije (MET). Na histoloÅ”kom nivou malo je podataka o znaÄaju aberantnog izražaja ovih proteina u KE.
Ispitanici i metode: U istraživanje je ukljuÄeno 86 bolesnica. Za imunohistokemijsku analizu napravljeni su tkivni rezovi primarnih tumora KE i njihovih metastaza te odreÄen postotak i jaÄina obojanosti tumorskih stanica na E-kaderin, Ī²-katenin i N-kaderin u centru tumora (CT), na invazivnoj fronti (IF), u limfovaskularnom prostoru (LVP) te u pripadajuÄim metastazama.
Rezultati: UtvrÄen je znaÄajan pad izražaja E-kaderina od CT prema IF (p< 0.0001) uz istovremeno pojaÄan izražaj N-kaderina (p=0.005) Å”to govori u prilog nastupu procesa EMT. UoÄeno je smanjenje membranskog Ī²-katenina od CT prema IF i LVP, dok nuklearni izražaj Ī²-katenina nije potvrÄen kao znaÄajni pokazatelj EMT. Usporedbom u odnosu na IF u metastazama je dokazan ponovni izražaj E-kaderina (p=0.049) i gubitak N-kaderina (p=0.008) Å”to govori u prilog aktivaciji MET. Negativni membranski Ī²-katenin na IF povezan je s dubokom invazijom miometrija (p=0.004) i znaÄajno kraÄim preživljenjem bolesnica (p=0.0439).
ZakljuÄak: Rezultati ovog istraživanja doprinijeli su boljem razumijevanju E-kaderina, N-kaderina i Ī²-katenina u procesu EMT i MET u KE. Imunohistokemijska analiza ispitivanih biljega dokazala je da postoji heterogenost u njihovom izražaju unutar tumora i u metastazama te poduprla hipotezu da je IF kljuÄna tumorska regija u kojoj nastupa EMT.Objectives: The key mechanism responsible for the progression of endometrial carcinoma (EC) is the activation of epithelial-mesenchymal transition (EMT) a process which helps epithelial cells to acquire mesenchymal phenotype. One of the hallmarks of EMT is the loss of the adhesion molecule E-cadherin, nuclear accumulation of Ī²-catenin and the acquisition of N-cadherin. Such tumor cells enter the invasion-metastasis cascade; while through the process of mesenchymal-epithelial transition (MET) re-establish their epithelial phenotype at distant sites. Little is known about aberrant expression of these proteins at histological level in EC.
Patients and Methods: The study included 86 patients. For the immunohistochemical analysis tissue samples of primary tumors and their metastases were selected and the expression of E-cadherin, N-cadherin and Ī²-catenin on the basis of percentage of positive tumor cells and staining intensity assessed in the central area (CA) of the tumor, at the invasive front (IF), in lymphovascular spaces (LVS) and metastases.
Results: We found a significantly reduced expression of E-cadherin at the IF when compared to CA (p <0.0001) and a simultaneous higher expression of N-cadherin (p=0.005) indicating the appearance of the EMT process. A less significant reduction of positive membrane Ī²-catenin from CA to IF was observed, while nuclear Ī²-catenin expression was not correlated to EMT. We confirmed a re-expression of E-cadherin in metastases when compared to the IF (p=0.049) and a simultaneous significant loss of N-cadherin (p=0.008) suggesting the activation of MET. Negative membrane Ī²-catenin at the IF was associated with deep myometrial invasion (p=0.004) and significantly shorter patient survival (p=0.0439).
Conclusion: The results of our research have contributed to a better understanding of the role of E-cadherin, N-cadherin and Ī²-catenin in the EMT and MET processes in EC. The immunohistochemical analysis of these markers confirmed that there is great heterogeneity within tumor areas in their expression as well as in metastases and support the hypothesis that the IF is the main tumor region in which EMT occurs
Äinitelji Bakterije I DomaÄina U Patogenezi Listerioze
Listeriosis is a zoonosis usually transmitted through contaminated food
or vertically from mother to foetus. In an immunocompetent, adult
person the infection results in transitory asymptomatic
gastrointestinal colonization or febrile, non-invasive gastroenteritis.
The infection of the foetus, newborn or immunocompromised person can
result in a serious invasive disease with high mortality rate. As a
facultative intracellular pathogen, Listeria monocytogenes is widely
used as model for studying cellular biology and mechanisms of cellular
immunity.Listerioza jest zoonoza do koje u veÄem broju sluÄajeva
dolazi nakon konzumacije zagaÄenih namirnica. U zdravih odraslih
osoba infekcija bakterijom Listeria monocytogenes posljeduje
prolaznom, asimptomatskom kolonizacijom crijeva, ili slikom neinvazivna
febrilnoga gastroenteritisa. Infekcija fetusa, novoroÄenÄeta,
ili imunokompromitirane osobe, može posljedovati razvojem
invazivne infekcije praÄene visokim postotkom smrtnosti. Zbog
svojstva unutarstaniÄnoga parazitiranja, bakterija Listeria
monocytogenes dugi se niz godina koristi kao oruÄe za
prouÄavanje staniÄne biologije i mehanizama staniÄne
imunosti