Metallothioneins (MTs) are phylogenetically old cysteine-rich proteins, which are implicated in a variety of physiological and pathological processes. Their growth-regulating, anti-apoptotic and ...anti-inflammatory functions have been attributed not only to intracellular free radical scavenging and to zinc and copper regulation but also to the ability of secreted MT to bind on surface lipoprotein receptor-megalin/LRP2, which enables the endocytosis of MT-I/II and a wide range of other functionally distinct ligands. In the present study, we analysed the expression pattern of both proteins in 55 cases of premalignant transformation of cervical squamous cells, i.e. in low- and high-grade squamous intraepithelial lesion (LSIL and HSIL). The data showed that in LSIL (cervical intraepithelial neoplasia CIN1;
N
= 25) MTs were present only in basal and parabasal cells and that megalin was only weakly expressed. In HSIL (CIN2;
N
= 15 and CIN 3/carcinoma in situ;
N
= 15), however, overexpression and co-localization of MT with megalin were found in the entire hyperplastic epithelium. Moreover, megalin immunoreactivity appeared on the glandular epithelium and vascular endothelium, as well as on lymphatic cells in stroma. Besides, multiple megalin-positive cells expressed phosphorylated Akt1, implying that MT- and/or megalin-dependent prosurvival signal transduction pathways might contribute to the development of severe cervical dysplasia. The data emphasize the diagnostic power of combined MT/megalin analysis in pre-cancer screening.
Plasmablastic lymphoma (PBL) is relatively new clinical entity described as a distinct subtype of diffuse large B-cell lymphoma (DLBCL). It is characterized by its aggressive nature and proliferation ...of large neoplastic cells resembling immunoblasts including cells with more obvious plasmacytic differentiation. In this case report, we describe an unexpected finding of PBL associated with a mature cystic teratoma of the ovary in a young immune competent woman.
A 19-year old woman was admitted to the hospital with generalized lymphadenopathy, a pelvic tumor mass measuring 35 × 30 cm and a 4 cm lump in her right breast. She underwent a right salpingo-oophorectomy, lymphadenectomy, splenectomy, omentectomy, and a right breast lumpectomy. On macroscopic examination the right ovary was replaced by a thick-walled multilocular cystic tumor. Upon incision, the cysts were filled with thick, greasy sebaceous material and hair and there were several solid nodules within the cyst walls. Histological examination revealed a mature cystic teratoma and malignant non-Hodgkin lymphoma (NHL) within the solid nodules. Tumor tissue from the right breast, spleen and lymph nodes, all had the same histological, NHL morphology. After extensive immunostaining, a diagnosis of PBL was made. Following surgery, the patient was treated with different chemotherapy regimens, without any significant regression of the disease, and died of multiple organ failure.
Primary NHL of the ovary is relatively rare occurrence while secondary involvement by lymphoma is much more common. PBL is a rare lymphoma, primarily reported in the jaw and oral mucosa, but also documented in extra-oral sites. To the best of our knowledge, this is the first case described in a mature ovarian cystic teratoma. Although the patient was HIV-negative and immune competent, she had progressive disease and died despite aggressive chemotherapy 11 months after the initial diagnosis.
Abstract Objective To evaluate the treatment and clinical outcome of patients with FIGO stage IA1 cervical squamous cell carcinoma (SCC). Methods Medical records, including 5-year follow-up, were ...reviewed for 276 patients with stage IA1 SCC. Results As definitive surgery, 152 (55.1%), 72 (26.1%), 40 (14.5%), and 12 (4.3%) patients underwent conization, hysterectomy, hysterectomy with pelvic lymphadenectomy (PL), and radical hysterectomy with PL, respectively. Among these groups, the 5-year recurrence-free rate was 94.1%, 98.6%, 95%, and 100%, respectively, and the survival rate was 98.7%, 98.6%, 100%, and 100%, respectively. Recurrent disease was identified among 12 (4.3%) patients, and was related to the depth of invasion ( P < 0.001). Eleven (4.0%) of 276 patients were found to have lymph vascular space invasion (LVSI). There were no positive lymph nodes among 52 patients who underwent PL, including those with LVSI. Conization was followed by hysterectomy in 49 patients. In these patients, residual intraepithelial neoplasia was found in 18 women, 3 of whom had no involved margins on previous conization. In the group of patients treated by conization, recurrence correlated with the status of the endocervical and lateral cone margin ( P < 0.001). Conclusion As a conservative approach, conization is an effective and reasonable treatment option for stage IA1 SCC, especially in actively reproductive women.
The majority of endometrial carcinoma are diagnosed at an early stage and exhibit a favorable prognosis. However, 10% to 15% of ECs recur and the majority are type II tumors which are high-grade ...carcinomas. The epithelial-mesenchymal transition (EMT) has been considered as a fundamental step for the development of the invasive phenotype of cancer cells. During EMT, many of epithelial surface markers, primarily E-cadherin disappear, and mesenchymal markers including N-cadherin gain. This feature resides predominantly at the invasive front (IF) of the tumor. Therefore, we examined the immunohistochemical expression of E-cadherin and N-cadherin at the IF, in central areas of the tumor and lymphovascular space, in type I and type II endometrial carcinoma. The association of each protein with the clinicopathologic features was also evaluated. Our results confirmed a stronger E-cadherin immunostaining in type I tumors indicating that the loss of E-cadherin may be responsible for a more aggressive behavior of type II ECs. In both types, E-cadherin was strongly expressed in central areas and the reactivity decreased toward the IF. On contrary, N-cadherin was overexpressed at the IF confirming an inverse relationship between these markers. In addition, a decrease in E-cadherin expression was observed in cells within the lymphovascular space. Downregulation of E-cadherin was associated only with high-grade tumors while no correlations between both markers and other clinicopathologic features were found. Our results confirm that EMT occurs at the IF that represents a critical interface between the tumor and the host.
Background. Massive ovarian edema (MOE) due to permeation of the ovarian lymphatics by metastatic carcinoma is rare, with a few cases reported to date.
Cases. We present two cases of MOE in patients ...with advanced carcinoma of the uterine cervix. Bilateral and unilateral MOEs in the first and second case, respectively, due to lymphatic permeation of the ovaries by metastatic squamous cell carcinoma and adenocarcinoma were found. Details of clinical history, operative procedure, pathological findings, therapy, and outcome are summarized.
Conclusion. MOE is the unusual manifestation of the metastatic disease of the ovaries from the carcinomas of the uterine cervix in these cases.
Novi model patogeneze karcinoma jajnika Babarović, Emina; Krašević, Maja; Eminović, Senija
Medicina fluminensis,
09/2016, Letnik:
52, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Karcinom jajnika je vodeći uzrok smrti među zloćudnim novotvorinama ženskog spolnog sustava. Usprkos pokušajima razvoja programa probira s ciljem ranog otkrivanja bolesti, kao i novim terapijskim ...pristupima, mortalitet nije značajno smanjen. Jedan od razloga ovog neuspjeha bio je slabo razumijevanje patogeneze karcinoma jajnika koji je smatran jedinstvenom bolešću. Nove spoznaje pokazuju da je karcinom jajnika vrlo heterogena bolest, koja se na temelju kliničkopatoloških karakteristika te molekularnih i genetičkih promjena može podijeliti u dvije skupine: tip 1 i tip 2 tumori. Ovaj novi model patogeneze karcinoma jajnika danas ima važan klinički i terapijski značaj
Little information is available regarding distribution of HPV types in different histological subtypes of adenocarcinoma (AC). Thus, in this study we examined the frequency of high-risk (hr) HPV ...types in AC, adenocarcinoma in situ (AIS) and adenosquamous carcinoma (ADSQ). A total of 102 cases of primary cervical adenocarcinoma (26 AIS and 76 invasive AC) obtained from pathology files from 1995-2006 were histologically subtyped. Our results demonstrated that endocervical type occupied the major subtype of AC (22/66) followed by ADSQ (17/66) where as in the group of AIS endocervical type (12/23) was followed by intestinal type of AIS (7/23). Successful DNA extraction was obtained in 89 samples; 81 out of 89 (91.0%) tested positive for HPV DNA. The prevalence of HPV DNA in AIS, AC and ADSQ was 91.3% (21/23), 90.9% (60/66) and 94.1% (16/17), respectively. We found HPV 18 type to be the most predominant type in AIS (11/21) and AC (17/60) followed by HPVof undeternmined type in AIS (3/21) and HPV 16 in AC (9/60) as the sole viral type. HPV 18 was most frequently detected type in all histological subtypes of AIS and AC. We have detected HPV DNA in all 5 samples of clear cell carcinoma (CCC), although other studies have reported a highly variable prevalence of HPVDNA in CCC. The most prevalent HPV type in ADSQ was HPV-16 followed by HPV 33 as single type. The observed overall predominance of HPV 18 in AIS (chi(2) = 6.109, p< or = 0.025) and AC (chi(2) = 8.927, p< or =0.01) as well as of HPV 16 in ADSQ (chi(2) = 10.164, p < or = 0.01) was statistically significant. Our data revealed statistically significant predominance of single hrHPV infections in AIS (16/21; chi(2) = 11.523, p < 0.001) and AC (37/60; X2 = 6.533, p < 0.025) whereas multiple hrHPV infections were more abundant in AC comparing to AIS (23/81and 5/81, respectively; chi(2) = 13.989, p< or =0.001).
The cancer stem cells (CSCs) represent a minority of tumor cells that are able to proliferate and self-renew and might be responsible for tumor initiation and maintenance. The CD133 and CD117 are the ...most commonly used markers for the putative CSCs, especially for the ovarian CSCs, but its clinical significance remains uncertain. The aim of this study was to compare the immunohistochemical expression of CD133 and CD117 in 64 primary ovarian high grade serous carcinoma and peritoneal metastasis, and to examine their potential clinical role. CD133 expression was mainly seen in the apical/endoluminal cell surface of tumor cells and was found in 61% of the carcinoma samples and 41% of the metastasis. The median of CD133 positive cells in tumors was 1 (0.1-7)%, and in metastases was 0.6 (0.1-6)%. CD117 expression appeared as a cytoplasmic and/or membranous stain and was found in 81% of the carcinoma samples and 77% of the metastasis. The median of CD117 positive cells in tumors was 1 (0.1-8)%, and in metastases was 0.1 (0.1-7)%. Multivariate analysis has shown that patients with high CD133 expression in tumor cells have significantly shorter disease free survival and overall survival (p=0.025 and p=0.014, respectively). Patients with high CD117 expression in tumor cells have significantly shorter disease free survival (p=0.031). Cox's proportional hazards model identified expression of CD133 protein in tumor as an independent prognostic factor. Our study indicates that the immunohistochemical assessment of CD133 and CD117 expression may have potential clinical value in predicting disease progression and prognosis in the high grade serous ovarian cancer. CD133 proved to be an independent prognostic factor in the high grade serous ovarian cancer patients.
Cilj: Istražiti međusobnu povezanost i prognostički značaj HPV statusa (humani papiloma-virus), HPV 16 genotipa i citomorfologije kod pacijentica s citološkim nalazom abnormalnih stanica pločastog ...epitela vrata maternice graničnog i blagog stupnja. Materijali i metode: U studiju su uključene pacijentice s inicijalnim citološkim nalazom vrata maternice atipičnih skvamoznih stanica neodređenog značenja (ASCUS, N = 160) i skvamozne intraepitelne lezije niskog stupnja (LSIL, N = 155). Analizirane su citomorfološke osobine koilocitoze, parakeratoze i makrocitoze. Sve pacijentice testirane su pomoću grupnog visokorizičnog HPV DNA testa (hybrid capture 2), a za pozitivne nalaze određen je genotip HPV-a pomoću molekularne metode INNO-LiPA HPV Genotyping v2. Pacijentice su praćene prosječno 26 mjeseci pomoću citologije, kolposkopije i patohistologije te je zabilježena regresija, stagnacija ili progresija bolesti. Rezultati: Najzastupljeniji HPV genotip je HPV 16. Nađen je kod 27,9 % ASCUS-a (N = 29) i u 16,5 % LSIL-a (N = 16), a njegova učestalost značajno je veća kod žena mlađih od 30 godina (P < 0,001). Makrocitoza se češće nalazi kod HR HPV negativnog ASCUS-a i LSIL-a (P < 0,05). Koilocitoza i parakeratoza nisu pokazale značajne razlike u odnosu na HR HPV status. U grupi LSIL odsutnost koilocitoze znatno je češća kod HPV 16 genotipa u odnosu na HPV ne-16 genotip (P = 0,002). Parakeratoza se češće nađe u HPV ne-16 grupi, ali razlika je statistički značajna samo kod LSIL-a (P = 0,005). Nepovoljan ishod bolesti zabilježen je u 25,3 % slučajeva ASCUS-a i 13,8 % LSIL-a. Progresija bolesti statistički je značajno povezana uz HR HPV pozitivitet (P < 0,001) i prisutnost HPV 16 genotipa (P < 0,001). Prisutnost koilocitoze, parakeratoze i makrocitoze u grupama ASCUS i LSIL nije povezana s nepovoljnim ishodom bolesti. Zaključak: U citološkim nalazima ASCUS i LSIL HPV 16 najčešće je nađeni genotip, a povezan je s češćom odsutnošću koilocitoze i parakeratoze. Nepovoljan ishod bolesti značajno je češći kod HR HPV i HPV 16 pozitivnih slučajeva, dok citomorfološke osobine koilocitoze, parakeratoze i makrocitoze nisu povezane s nepovoljnim ishodom bolesti. Ovi rezultati mogu pridonijeti optimiziranju praćenja i obrade pacijentica s inicijalnim citološkim nalazima ASCUS i LSIL te utjecati na moguće modifikacije usvojenih kliničkih i citoloških smjernica za lezije vrata maternice.
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.
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