To gain insight into the role and association of cell cycle and apoptosis regulatory proteins and telomerase activity in the course of progression of melanocitic lesions we have examined ...immunohistochemicaly, expression and the distribution of p53, bcl-2, Ki-67 and telomerase in 25 samples of common and dysplastic nevi, and 45 samples of primary invasive melanomas. Protein p53 expression was significantly increased in dysplastic as compared with common nevi and melanomas (p < 0.001). Bcl-2 protein expression was significantly increased in melanomas as compared with common aquired and dysplastic nevi (p = 0.001). Nevi and melanomas exhibited clear-cut differences in terms of Ki-67 expression. Telomerase expression was significantly increased in melanomas as compared with common acquired (p = 0.014) and dysplastic nevi (p < 0.001). Enhanced telomerase activity in association with increased bcl-2 expression in the course of melanoma progression could contribute to development and progression of melanoma.
Non-Hodgkin lymphoma (NHL) is one of the most common malignancies whose incidence increases, and the treatment results are not satisfactory. The aim of this study was to determine the capacity of NHL ...to produce MCP-1, chemokine that induces chemotaxis of macrophages and lymphoid cells. The mRNA expression and protein MCP-1 expression were determined in the samples of 20 patients with NHL and 8 reactive tonsils. MCP-1 mRNA was detected in 8/8 tonsils and in 19/20 patients with NHL by real-time PCR analysis. In addition, the amount of detected MCP-1 cDNA was significantly higher in patients with limited stage, good IPI, normal level of fibrinogen and LDH. Finally, in patients with aggressive NHL, the level of MCP-1 cDNA was higher than in indolent tumours. Immunohistochemical analysis revealed that majority of stromal elements such as macrophages, endothelial and smooth muscle cells in reactive as well as in neoplastic lymphoid tissue showed strong cytoplasmic MCP-1 expression. Moderate cytoplasmic MCP-1 expression was also observed in reactive lymphocytes, while tumour cells of indolent NHL were mostly pale in comparison with aggressive lymphomas which predominantly demonstrated intense MCP-1 staining. These intriguing preliminary results emphasize the need for further investigations that must be conducted on the representative sample with concordant measurement of serum MCP-1 level.
There are no data obtained in biopsy material on the prevalence of human papillomavirus (HPV) and HPV genotypes in Croatian women with cervical carcinoma and precursor lesions. Therefore, the ...prevalence of HPVand HPVgenotypes was investigated in archival material of cervical carcinoma and precursor lesions kept at Department of Pathology, School of Medicine, University of Rijeka. DNA was isolated from formalin fixed, paraffin embedded tissue, histologically classified as cervical intraepithelial neoplasia (CIN) III (n =43), squamous cell carcinoma (SCC) (n =54) and adenocarcinoma (ADC) (n =40). HPV testing was performed bypolimerase chain reaction (PCR) using generic and genotype specific primers. The prevalence of HPV DNA was 93.02%, 92.59%, and 92.5% in CIN III, SCC and ADC, respectively. In CIN III and SCC, HPV-16 was the most common high-risk genotype, identified in 65% and 52%, followed by HPV-18 in 22.5% and 28% of cases, respectively. HPV-18 showed a statistically significant prevalence in ADC (67.6%) as compared with SCC (chi(2)=9.924; p_ 0.01). Study results revealed a high prevalence of HPV-DNA in examined cervical lesions (>90%). HPV-16 predominated in SCC and HPV-18 in ADC. Single infection was more frequently present than multiple infections in all three histological groups.
Human papillomavirus (HPV) infection has been identified as major risk factor for cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. About 40 HPV viral types are commonly found in ...the genital tract. Most HPV infections resolve spontaneously, while persistent infection with oncogenic types, namely HPV 16 and 18 is necessary for CIN to occur and progress to cancer. Cervical screening is presently based on the Pap smear that is designed to diagnose precancerous lesions and cervical cancer The aim of this study was to investigate the prevalence of HPV DNA and to determine HPV types distribution among 361 women attending regular gynecological visit. There were 205 women (29+/-8 years old) without determined abnormal cervical lesions and 156 women (34+/-15 years old) with abnormal Pap smear; low grade squamous intraepitehelial lesions (LSIL, n=69), high grade squamous intraepithelial lesions (HSIL, n=72) and atypical squamous cells of undetermined significance (ASCUS, n=15). HPV DNA detection and genotyping was performed by Hybrid Capture 2 assay and additionally by consensus and type-specific primers directed PCR. The overall prevalence of high-risk HPV (hrHPV) in women with abnormal Pap smears was 67.9% (106/156), of which in ASCUS 33.4% (5/15), LSIL 62.3% (43/69) and HSIL 80.6% (58/72). In HPV positive specimens, HPV 16 was found as predominant type in 60.4% cases, followed by HPV 31 (8.5%), HPV 33 (6.6%) and HPV 18 (3.7%). In the group of women without obvious cervical changes the overall hrHPV prevalence was 35.6% with HPV 16 found in 43.8% cases, followed by HPV 31 (17.8%), HPV33 (9.5%) and HPV18 (6.8%). In both study groups, women with and without cervical lesions, the prevalence of HPVof indeterminate type was 14.2% and 13.7%, respectively. Our results indicate that cervical intraepithelial lesions are largely associated with HPV type 16, followed by HPV types 31, 33, 18 and HPV of indeterminate type. Although there is a significant difference in hrHPV DNA prevalence among two groups, no significant differences between particular hrHPV types distribution were observed.
Cilj rada: Analizirati funkcionalni i onkološki ishod bolesnika s ranim stadijem karcinoma grkljana, liječenih frontolateralnom laringektomijom. Bolesnici i metode: U retrospektivno istraživanje ...uključeno je 45 kirurški liječenih bolesnika s ranim stadijem karcinoma grkljana. Funkcionalni ishod uključivao je procjenu respiratorne i fonatorne funkcije, te akta gutanja. Respiratorna funkcija grkljana smatrana je primjerenom u slučaju nepostojanja stenoza i uspješnog dekanilmana. Za evaluaciju glasa korištene su GRBAS skala, Voice Handicap Index 30 upitnik i spektralna akustična analiza glasa. Akt gutanja procjenjivan je na osnovu anamnestičkih podataka i fiberlaringoskopskog pregleda. Onkološki ishod prikazan je Kaplan-Meierovim krivuljama ukupnog preživljenja (overall survival), preživljenja bez bolesti (disease free survival) i preživljenja vezanog uz bolest (disease specific survival). Rezultati: Od ukupno 45 bolesnika, 3 su bila ženskog, a 42 muškog spola. Medijan dobi iznosio je 64 godine (raspon 44-79). Svi su se tumori nalazili u glotičkoj regiji, te su svrstani u T1 (60%) ili T2 (40%) klasifikaciju bolesti. Postoperativna radioterapija primijenjena je u 15 (33,3%) bolesnika zbog limfovaskularne invazije tumora ili R1 resekcijskih rubova. Svi su bolesnici imali urednu respiratornu funkciju te uredno izvršen dekanilman. Kod niti jednog bolesnika nismo verificirali poremećaj gutanja. Analiza fonatorne funkcije pokazala je umjerene teškoće bolesnika vezane uz kvalitetu glasa. Procjenom onkološkog ishoda utvrđeno je da je petogodišnje preživljenje vezano uz bolest iznosilo 100%, petogodišnje ukupno preživljenje 93,3%, dok je petogodišnje preživljenje bez bolesti iznosilo 86,7%. U sklopu praćenja bolesnika (medijan 86,2 mjeseca), dva su bolesnika razvila lokalni, a jedan regionalni recidiv bolesti. Zaključak: Iako noviji modaliteti liječenja nude bolji funkcionalni ishod što se najviše očituje u kvaliteti glasa, frontolateralna laringektomija nudi podjednak onkološki ishod i vrijedna je alternativna kirurška opcija u pomno izabranim slučajevima.
We report a case of a 76-year-old woman with concurrent onset of two primary cutaneous malignancies, one at the fourth finger and another at the dorsum of the same hand. The patient was on long-term ...therapy with hydroxyurea (HU) for polycythemia vera. Histopathologic and immunohistochemical studies revealed two different malignant cutaneous lesions, i.e. basal cell carcinoma (positive for bcl-2 and negative for vimentin, EMA and CK5/6) and poorly differentiated sarcomatoid squamous cell carcinoma (positive for vimentin, EMA and cytokeratins CK5/6, and negative for bcl-2). In addition, p53 was positive in approximately 50% of squamous cell carcinoma cells and in almost all basal cell carcinoma cells. The presence of low-risk human papillomavirus (HPV, types 6, 11) was verified by polymerase chain reaction, but only in the surrounding normal skin tissue, whereas HPV infection could not be detected in either carcinoma. In this patient, concurrence of two different skin carcinomas on sun-exposed skin, in the absence of HPV, suggest direct involvement of potentially mutagenic HU therapy, through influence on DNA synthesis and repair mechanisms, in conjunction with ultraviolet exposure. Therefore, we suggest that in patients on HU therapy with cutaneous side effects, referral to a dermatologist should be obligatory.
The purpose of this study was to compare vascularization of the nasal mucous membrane among non-allergic, non-treated allergic and allergic patients treated with mometasone furoate, by means of the ...stereology method in quantitative analysis. Three groups of patients (GP), each containing 10 patients were examined. The first group (GP 1) had a negative inhalatory allergen test while the second (GP 2) and third (GP 3) group both had positive results with the same test. GP 3 included allergic patients treated with mometasone furoate for 15 days before analysis, when a small piece of the nasal mucous membrane was taken from the frontal pole of the lower nasal shell. The specimens were examined immunohistochemically for expression of CD31 and VEGF-C. Vascular phase was determined by using length density (L(v)). Differences in CD31 and VEGF-C expression were compared using one-way ANOVA and Tukey HSD post-hoc tests. CD31 expression in GP 1 had significantly lower values than in the GP 2 and GP 3 groups (p < 0.001). VEGF-C expression in GP 1 was significantly lower than in GP 2 (p = 0.007), but not in GP 3 (p = 0.292). We have shown that 15-day treatment with mometasone furoate results in a significant reduction of the density of vascular elements in allergic patients.
Cilj: Istražiti utjecaj angiogenih parametara, izražaja osteopontina (OPN) i vaskularnog endotelnog čimbenika rasta (VEGF; engl. vascular endothelial growth factor) u koštanoj srži na odgovor na prvu ...liniju terapije u pacijenata s multiplim mijelomom (MM). Ispitanici i metode: U istraživanje je uključeno 68 pacijenata s MM-om, liječenih na Odjelu hematologije Kliničkog bolničkog centra u Rijeci. Za kvantifikaciju angiogenih parametara uz klasičnu metodu utvrđivanja gustoće krvnih žila (MVD; engl. microvessel density) koristili smo i računalno potpomognutu analizu slike koja nam je omogućila izračunavanje broja krvnih žila po mm2, površine krvnih žila po mm2, srednjeg promjera krvnih žila i ukupne vaskularne površine (TVA; engl. total vascular surface) na bioptičkim uzorcima koštane srži obojanim s anti-CD34. Za određivanje izražaja OPN-a i VEGF-a u plazma stanicama korištena je dvostruka imunohistokemijska metoda CD138+OPN i CD138+VEGF. Rezultati: Utvrđeno je da su viši angiogeni parametri, MVD (P = 0,004) i broj krvnih žila po mm2 (P = 0,028) značajni negativni prognostički pokazatelji odgovora na prvu liniju terapije u pacijenata s MM-om. Zaključak: Objektivna metoda procjene angiogeneze u uzorcima koštane srži mogla bi postati dio rutinske patohistološke obrade pacijenata koja bi pomogla u prepoznavanju podskupina pacijenata s eventualnim agresivnijim tijekom i lošijim odgovorom na terapiju.
Internistička patologija relativno je nov pojam koji obuhvaća dio patologije koji se bavi patohistološkom dijagnostikom pretežito netumorskih stanja, a u manjoj mjeri tumora, u različitim granama ...interne medicine, poput pulmologije, hematologije, nefrologije, gastroenterologije, dermatologije i imunologije. Uvidom u morfološke promjene bolesnih tkiva patolog postavlja dijagnozu koja se uz dodatne kliničke podatke dorađuje, međutim, patolog često odmah postavlja i definitivnu dijagnozu koja određuje daljnji tijek liječenja pacijenta. Internistička patologija obuhvaća vrlo složen i sofisticiran sustav dijagnostike u patologiji koji implementira bazičnu patohistološku dijagnostiku upotpunjenu histokemijskim, imunohistokemijskim, imunofluorescentnim i molekularnim tehnikama te elektronskomikroskopskom analizom. Oskudnost tkiva dobivenog pretežito tijekom različitih endoskopskih procedura te putem biopsije iglom jedna je od osobitosti ove grane patologije. Interpretacija promjena u analiziranim stanicama i tkivima često je ograničena dostupnošću kliničkih podataka o pacijentovu stanju, a korelacija morfoloških promjena s kliničkim podacima neophodna za ispravno postavljanje konačne dijagnoze. Iz navedenog se može zaključiti kako je internistička patologija dijagnostički vrlo zahtjevna i izazovna grana patologije koja koristi najsuvremenije pomoćne alate u cilju spoznaje patološkog supstrata bolesti, kako poznatih tako i novih internističkih entiteta.
PDF