Imunohistokemijska izraženost i prognostička vrijednost proteina nm23-H1 i COX-2 u papilarnom karcinomu štitnjače

Papillary thyroid carcinoma is an epithelial tumor that frequently affects young women. Although it has an excellent prognosis, there is a small group of patients who present a tumor with a more aggressive behavior. So far, the research directed to the specific age and gender groups, histological variants, tumor diameter, intraglandular spread and the presence of metastases have not succeeded in definitely identifying the group of tumors with aggressive behavior, although some studies have shown the age, tumor diameter, tumor local invasiveness, metastases to regional lymph nodes and distant metastasis as independent prognostic factors. The nm23 gene belongs to a group of tumor suppressors, whereas COX-2 is an enzyme, expressed at inflammation sites and in many different carcinomas. Both proteins have been separately studied in papillary thyroid cancer, and the obtained results were contradictory. However, it has been shown in vitro that COX-2 transcription depends on nm23-H1 expression. The hypothesis of this study was based on importance of nm23-H1 and COX-2 expression in predicting a smaller group of patients with a biologically more aggressive primary tumor at the time of diagnosis. A total of 130 samples of papillary thyroid carcinoma tissue was analyzed in this study. The following parameters were analyzed: the tumor sub-type, the presence of lymphocyte inflammatory infiltrate, intraglandular dissemination, benign changes in the thyroid gland and regional metastases in lymph nodes. For detection of nm23-H1 and COX-2, immunohistochemical staining have been performed with highly specific monoclonal antibodies. Immunohistochemical analysis results show middle-strong and very positive staining for both proteins, in majority of tumors. The expression of COX-2 was always joined with nm23-H1 positivity (P<0,001). The expression of nm23-H1 and COX-2 is not related to the patient's age or gender, tumor diameter, intraglandular dissemination of the tumor and the presence of metastasis in regional lymph nodes. The nm23-H1 median expression is significantly higher in the classical and follicular histological variant of papillary carcinoma, compared to other histological variants (P=0,044). On the other hand, the median COX-2 expression is significantly higher in the follicular histological variant, and decreased in the diffuse-sclerosing variant (P=0,014). The presence of lymphocyte inflammatory infiltrate in the tumor is connected to the presence of thyroiditis in the surrounding, non-tumorous tissue of the thyroid gland (P<0,001), but it does not relate to the expression of nm23-H1 and COX-2 in the tumorous tissue. Finaly, COX-2 expression in papillary microcarcinoma is related to the metastases to regional lymph nodes (P=0,017). The results of this research show that there is relation in the expression of nm23-H1 and COX-2 in the papillary carcinoma of the thyroid gland, particularly with respect to histological sub-variants. Although, their expression does not help in identifying the group of more aggressive papillary carcinomas, it could help in identifying the group of more aggressive papillary thyroid microcarcinoma

Survivin i proliferativni indeks Ki67 u raku dojke

Survivin is a member of the inhibitor of apoptosis (IAP) family. It is also involved in the regulation of cell division.Survivin is widely expressed in foetal tissues and in human cancers, but generally not in normal adult tissue. This study examined the expression of survivin protein in a series of 50 cases of invasive primary breast carcinoma. Our study comprised 50 cases of breast cancer, 10 of each immunophenotype. All tumours were diagnosed as invasive ductal carcinoma (Not Otherwise Specifi ed, NOS). Formalin-fi xed, paraffi n-embedded tissue sections were immunostained for survivin. Survivin immunoreactivity was evaluated as follows: 0(0-5% positive cells); 1(5–20%); 2(21–50%); 3(51–75%); 4(>76%) with cutoff value of 20% that was established as a positive result. Immunohistochemical analysis showed positive expression for survivin in 18 of 50 cases (36%) of breast carcinomas of TNM stages I to III. In previous studies, there was significant relationship between survivin expression and negative prognostic factors like larger tumour size, higher histologic grade and negative hormonal status. What we should emphasize in our study is the correlation between HER2 positive tumours and survivin expression (P=0.007) and strong association of survivin expression in cytoplasm in HER2 positive tumours as a predictor of unfavourable outcome. Further larger studies are needed in future to explore and explain the facts about survivin and its connection with breast cancer.Survivin je protein koji je član obitelji inhibitora apoptoze, a uključen je i u regulaciju stanične diobe. Široko je rasprostranjen u fetalnim tkivima i ljudskim tumorima, ali se u pravilu ne javlja u normalnim odraslim tkivima. Studijom smo ispitali izražajnost survivina u seriji od 50 slučajeva invazivnog primarnog karcinoma dojke. Obrađeno je 50 slučajeva, po 10 od svakog imunofenotipa. Svi tumori su dijagnosticirani kao invazivni duktalni karcinom (NOS). Dijelovi tumorskog tkiva su fiksirani u formalinu i uklopljeni u parafinske kocke te je napravljena imunohistokemijska obrada na survivin. Imunoreaktivnost survivina je procijenjena: 0 (0-5% pozitivnih tumorskih stanica); 1 (5-20%); 2 (21-50%); 3 (51-75%) i 4(> 76%) uz graničnu vrijednost od 20%, koja je ustanovljena kao pozitivan rezultat. Imunohistokemijska analiza pokazala je pozitivnu izraženost survivina u 18 slučajeva (36%) TNM stadija I do III. U prethodnim studijama vidljiva je značajna povezanost izraženosti survivina i negativnih prognostičkih čimbenika kao što su veličina tumora, visoki histološki gradus i negativni hormonalni status. Treba naglasiti da je prediktor nepovoljnog ishoda pozitivna korelacija HER2 pozitivnih tumora i izražajnosti survivina u njihovoj citoplazmi (P=0.007). Potrebne su buduće studije koje će istražiti i objasniti činjenice vezane uz survivin i njegov odnos s karcinomom dojke

Prikaz slučaja rijetkog unutarparenhimnog leiomioma dojke – dijagnostičke i patohistološke značajke

Leiomyomas are one of the rarest neoplasms of the breast. Intraparenchymal leiomyomas can present a diagnostic challenge, as they can resemble other benign, and more importantly, malignant lesions - especially leiomyosarcomas. Here we report a case of a 28-year old female patient with a palpable mass in the right upper quadrant of the right breast and present diagnostic and histopathological features, with special reference to magnetic resonance imaging.Leiomiomi su izrazito rijetki tumori dojke. Unutarparenhimni leiomiomi predstavljaju dijagnostički izazov, jer mogu nalikovati na druge dobroćudne i zloćudne tvorevine, posebice na leiomiosarkom. U radu je prikazan slučaj 28-godišnje žene s opipljivom masom u desnoj gornjoj četvrtini desne dojke. Opisane su dijagnostičke i patohistološke značajke nađenog tumora, s posebnim osvrtom na magnetsku rezonanciju

Kolorektalni karcinom - patohistološki standardi

Colorectal carcinoma is the third most common cancer site in Croatia, according to the data published by the The Croatian National Cancer Registry. In the last decade, the knowledge about pathogenesis and molecular background of colorectal carcinoma has increased dramatically. More than 90% of colorectal carcinomas are adenocarcinomas originating from epithelial cells of the colorectal mucosa. Tumor staging is the most important prognostic predictor of clinical outcome for patients with colorectal carcinoma. The TNM classification has nowdays replaced other classification systems (Dukes, Astler-Coller) and serves as golden standard in everyday practise.In 2012, 5th Croatian Congress for Pathology resulted in uniform standard for pathologic reporting for all cancer sites. The future for colorectal cancer prognosis and therapy is to discover new molecular subtypes of colorectal cancer which represents the future of personalized oncology and will guide drug-development strategies.Prema podacima Registra za rak karcinom kolorektuma je treće najčešće tumorsko sijelo u Hrvatskoj. U zadnjih deset godina imamo brojna nova saznanja o patogenezi i molekularnim karakteristikama karcinoma kolorektuma. Više od 90% kolorektalnih karcinoma su adenokarcinomi po histološkom tipu, porijekla epitelnih stanica kolorektalne mukoze. Stadij tumora je najbitniji prognostički čimbenik za pacijente s tom bolešću. U današnje je vrijeme TNM klasifikacija zamijenila druge klasifikacijske sustave (Dukes, Astler-Coller) i koristi se kao zlatni standard u svakodnevnoj praksi. 2012. na Hrvatskom kongresu patologa, doneseni su standardi za sva tumorska sjela, koje mora zadovoljavati svaki patohistološki nalaz. Budućnost prognoze i terapije kolorektalnog karcinoma je otkriće novih molekularnih podtipova prema kojima bi se određivala personalizirana onkološka terapija te odredile nove strategije liječenja

Tumorska kalcinoza prikazana kao mekotkivna tvorba u 16-godišnjeg bolesnika

Background: Tumoral calcinosis is a rare clinicopathological condition characterized by periarticular tumor-like calcium deposits most commonly found around major joints, especially the hips, shoulders and elbows. Tumoral calcinosis is not primarily a bone-or cartilage-forming lesion, but it can closely simulate osteocartilaginous tumors. These lesions are predominantly seen during the first two decades of life and may be multicentric or bilateral. Laboratory analysis frequently shows high serum phosphate but normal serum calcium levels. A 16 year old male presented with a huge mass in the left hip which had been growing for a month. MR detected large tumor mass in the left gluteal region with possible infi ltration of m.gluteus maximus. Soft tissue mass was surgically resected, measuring 24 cm in diameter. Histologically, it was composed of multiple large cystic spaces with nodules of amorphous calcifi ed deposits surrounded by multinucleated giant cells and mononuclear infi ltrates. The lesion was poorly circumscribed with infi ltration into surrounding striated muscle. Tumoral calcinosis is an uncommon and benign condition that generally occurs as a complication of trauma or renal dialysis, and is rarely seen in familial and sporadic cases. It can occur in a variety of clinical sett ings: primary normophosphatemic, primary hyperphosphatemic and secondary tumoral calcinosis occuring along with disorders that are capable of producing soft tissue calcifi cation. Histologically, tumoral calcinosis is characterized by amorphous calcifi ed deposits in the background of granulomatous appearance with multinucleated giant cells and other infl ammatory cells. The diff erential diagnosis is broad and includes all tumoral calcinosis-like lesions that lead to abnormal dystrophic or metastatic calcium deposition in soft tissues. Surgical excision is the primary treatment.Tumorska kalcinoza je rijetko kliničko-patološko stanje obilježeno periartikularnim kalcificiranim depozitima nalik tumorima najčešće smještenim u području kuka, ramena i lakta. Tumorska kalcinoza nije primarna bolest koštano-hrskavičnog sustava, iako svojim obilježjima nalikuje i upućuje na tumor koštano-hrskavičnog sustava. Izraslina se obično pojavljuje multicentrično i bilateralno u prva dva desetljeća života. Laboratorijska analiza učestalo pokazuje povećanu razinu fosfata i normalnu razinu kalcija u serumu. Lječeni dječak (16 god) imao je veliku tvorbu u području lijevog kuka koja je rasla mjesecima. MR je prikazala izraslinu s mogućom infiltracijom velikog glutealnog mišića. Kirurški je odstranjena neoštro ograničena tvorba najvećeg promjera 24 cm koja je infiltrirala strijatni mišić. Histološki je bila građena od brojnih velikih cističnih prostora s okruglastim kalcificiranim nakupinama okruženim multinuklearnim orijaškim stanicama i mononuklearnim upalnim infi ltratom.Tumorska kalcinoza je rijetko, benigno stanje koje se uglavnom očituje kao komplikacija traume ili bubrežne dijalize, a rijetko se viđa i u obiteljskom i u sporadičnom obliku. Može se očitovati u nekoliko kliničkih oblika: primarna normofosfatemična, primarna hiperfosfatemična i sekundarna tumorska kalcinoza. Neovisno o obliku uvijek je prisutan poremećaj s nakupljanjem kalcifikata u mekom tkivu. Histološki se vide amorfni kalcificirani depoziti okruženi granulomatoznom upalom s multinuklearnim orijaškim i mononuklearnim upalnim stanicama. Diferencijalna dijagnoza obuhvaća široki spektar promjena koje uključuju pretjerano distrofično i metastatsko nakupljanje kalcija u mekom tkivu. Kirurška ekscizija je izbor liječenja

Counteraction of perforated cecum lesions in rats: effects of pentadecapeptide BPC 157, L-NAME and L-arginine

AIM: To study the counteraction of perforated cecum lesion using BPC 157 and nitric oxide (NO) system agents. ----- METHODS: Alongside with the agents' application (after 1 min, medication (/kg, 10 mL/2 min bath/rat) includes: BPC 157 (10 μg), L-NAME (5 mg), L-arginine (100mg) alone or combined, and saline baths (controls)) on the rat perforate cecum injury, we continuously assessed the gross reappearance of the vessels (USB microcamera) quickly propagating toward the defect at the cecum surface, defect contraction, bleeding attenuation, MDA- and NO-levels in cecum tissue at 15 min, and severity of cecum lesions and adhesions at 1 and 7 d. ----- RESULTS: Post-injury, during/after a saline bath, the number of vessels was significantly reduced, the defect was slightly narrowed, bleeding was significant and MDA-levels increased and NO-levels decreased. BPC 157 bath: the vessel presentation was markedly increased, the defect was noticeably narrowed, the bleeding time was shortened and MDA- and NO-levels remained normal. L-NAME: reduced vessel presentation but not more than the control, did not change defect and shortened bleeding. L-arginine: exhibited less vessel reduction, did not change the defect and prolonged bleeding. In combination, mutual counteraction occurred (L-NAME + L-arginine) or the presentation was similar to that of BPC 157 rats (BPC 157 + L-NAME; BPC 157 + L-arginine; BPC 157 + L-NAME + L-arginine), except the defect did not change. Thereby at day 1 and 7, saline, L-NAME, L-arginine and L-NAME + L-arginine failed (defect was still open and large adhesions present). ----- CONCLUSION: The therapeutic effect was achieved with BPC 157 alone or in combination with L-NAME and L-arginine as it was able to consolidate the stimulating and inhibiting effects of the NO-system towards more effective healing recruiting vessels

Fetal indusium griseum is a possible biomarker of the regularity of brain midline development in 3T MR imaging: A retrospective observational study

INTRODUCTION: This study aimed to assess the visibility of the indusium griseum (IG) in magnetic resonance (MR) scans of the human fetal brain and to evaluate its reliability as an imaging biomarker of the normality of brain midline development. MATERIAL AND METHODS: The retrospective observational study encompassed T2-w 3T MR images from 90 post-mortem fetal brains and immunohistochemical sections from 41 fetal brains (16-40 gestational weeks) without cerebral pathology. Three raters independently inspected and evaluated the visibility of IG in post-mortem and in vivo MR scans. Weighted kappa statistics and regression analysis were used to determine inter- and intra-rater agreement and the type and strength of the association of IG visibility with gestational age. RESULTS: The visibility of the IG was the highest between the 25 and 30 gestational week period, with a very good inter-rater variability (kappa 0.623-0.709) and excellent intra-rater variability (kappa 0.81-0.93). The immunochemical analysis of the histoarchitecture of IG discloses the expression of highly hydrated extracellular molecules in IG as the substrate of higher signal intensity and best visibility of IG during the mid-fetal period. CONCLUSIONS: The knowledge of developmental brain histology and fetal age allows us to predict the IG-visibility in magnetic resonance imaging (MRI) and use it as a biomarker to evaluate the morphogenesis of the brain midline. As a biomarker, IG is significant for post-mortem pathological examination by MRI. Therefore, in the clinical in vivo imaging examination, IG should be anticipated when an assessment of the brain midline structures is needed in mid-gestation, including corpus callosum thickness measurements

Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine

AIM: To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide (NO) system involvement. ----- METHODS: Male Wistar rats underwent superior anterior pancreaticoduodenal vein (SAPDV)-ligation and were treated with a bath at the ligated SAPDV site (BPC 157 10 μg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 mL bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation (filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein (IAPDV) and superior mesenteric vein (SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO- and oxidative stress [malondialdehyde (MDA)]-levels in duodenum. ----- RESULTS: Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal tissues. ----- CONCLUSION: BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, an effect related to the NO system and reduction of free radical formation

Inflammation in prostatic hyperplasia and carcinoma-basic scientific approach

Chronic inflammation is associated with both benign conditions and cancer. Likewise, inflammatory cells are quite common in benign prostatic hyperplasia (BPH) and prostatic tissue harboring cancer. Triggers that activate inflammatory pathways in the prostate remain a subject of argument and are likely to be multifactorial, some of these being bacterial antigens, different chemical irritations, and metabolic disorders. Acute and chronic inflammation in prostate leads to accumulation of immunocompetent cells, mainly T lymphocytes and macrophages, but also neutrophils, eosinophils, and mast cells, depending on the type of offending agent. Inflammatory processes activate hyperproliferative programs resulting in nodules seen in BPH, but are also important in creating suitable microenvironment for cancer growth and progression. Inflammatory cells have mostly been shown to have a protumoral effect such as tumor-associated macrophages, but some cell types such as mast cells have antitumoral effects. This review outlines the recent findings and theories supporting the role of inflammatory responses as drivers of both benign and malignant epithelial processes in the prostate gland