Clinical and immunohistochemical caracteristcs of adrenocortical carcinomas and their influence on survival

Uvod: Karcinomi kore nadbubrežne žlezde su agresivni tumori sa lošom prognozom, uprkos multimodalnom tretmanu koji se primenjuje u njihovom lečenju. Veoma su retkici zbog toga još uvek nedovoljno istraženi. Cilj: Cilj našeg rada je da se odrede osnovne demografske, kliničke i imunohistopatološke karakteristike obolelih od karcinoma kore nadbubrežne žlezde, prikažu opšte stope preživljavanja, analizira uticaj pojedinih prognostičkih faktora na dužinu preživljavanja i identifikuju pozitivni i negativni prediktori preživljavanja. Materijal i metod rada: Istraživanjem su obuhvaćena 72 pacijenta (42 žene i 30 muškaraca) sa karcinomom kore nadbubrežne žlezde. Analizirane su demografske i kliničke karakteristike obolelih, karakteristike tumora, primenjena terapija i preživljavanje kod obolelih. Posebno su analizirane imunohistohemiske karakteristike tumora i njihovo bojenje na sledeće markere: MMP9, melan A, inhibin, caltretinin, D240 i synaptophysin kao i marker tumorske proleferacije Ki67. U statističkoj analizi podataka korišćene su Kaplan-Mejerove krive preživljavanja i log rank test, radi odreĎivanja opštih i specifičnih stopa preživljavanje i Cox-ov regresioni model. Rezulati: Prosečna starost obolelih je iznosila 50 godina. Samo 2 (3,1%) obolela su dijagnostikovana u I stadijumu bolesti, dok je skoro polovina bila u II stadijumu bolesti. Prosečni dijametar tumora iznosio je 98 mm, a prosečna težina 322 grama. U vreme postavljanja dijagnoze regionalne limfogene metastaze je imalo 12%, a udaljene metastaze 9% obolelih. Približno podjednako karcinom kore je bio lokalizovan u levoj i desnoj nadbubrežnoj žlezdi. Dve trećine obolelih je operisano kroz subtotalnu laparotomiju, jedna četvrtina transdorzačnim pristupom, a niko nije operisan endoskpskim pristupom. Kod skoro 90% obolelih načinjena je potencijalno radikalna operacija (adrenalektomija sa ili bez resekcije okolnih organa). Terapija mitotanom je bila jedina vrsta hemioterapije koja je sprovedena kod obolelih. Oko četvrtina obolelih je imalo hormonski aktivni karcinom kore nadbubrežne žlezde. U vreme kada je studija završena skoro polovina obolelih je još uvek bila živa. Jednogodišnje preživljavanje kod obolelih od karcinoma kore nadbubrežne žlezde je iznosilo 52,5%, petogodišnje 41,1%, a desetogodišnje preživljavanje 16,4%. Medijana preživljavanja je iznosila 36 meseci...Introduction: Adrenocortical carcinomas (ACC) are aggressive tumours with poor prognosis, even with multimodal treatment that is used in their treatment. Since they are rare tumours they have not been studied sufficiently. Aim: The aim of our study was to examine demographic, clinical and immunohistochemical characteristics of patients with ACC, to determine general survival rates, analyse the effect of certain prognostic factors on the survival rate, as well as to identify positive and negative predictors of survival. Material and methods: The study included 72 patients (42 women and 30 men) with ACC. We analysed demographic and clinical characteristics of the patients, tumour characteristics, the therapy they received and survival rates of the patients. We also specifically analysed immunohistochemical characteristics of the tumour using the following staining protocols: MMP9, melan A, inhibin, calretinin, D240 and synaptophysin as well as tumour proliferation marker Ki67. In statistical analysis we used Kaplan-Meier's survival curves and log-rank test to estimate general and specific survival rates and the logistic regression model. Results: The mean age of the patients in the study was 50 years. Only two patients (3.1%) were diagnosed in stage I of the disease, while more than half were in stage II of the disease. The mean size of the tumour was 98 mm and mean weight was 322 grams. At time of diagnosis regional lymph metastasis were present in 12% while distant metastasis were present in 9% of patients. ACC was nearly evenly distributed between the left and the right adrenal gland. There was nearly an even distribution between left and right localization of ACC. Two thirds of the patients were operated through a subcostal laparotomy and one quarter through a transdorsal approach. An endoscopic approach was not used in any of the cases. Nearly 90% of the patients were treated with a potentially radical operation (adrenalectomy with or without resection of surrounding tissue). Therapy with mitotane was the only kind of chemotherapy used. A hormonal active tumour was present in quarter of patients with ACC. At the time of the study nearly half of the patients were still alive. One-year survival of patients with ACC was 52.5%, five-year survival was 41.1%, and ten-year survival was 16.4%. Median survival was 36 months..

Cyclin d1 and p57 expression in relation to clinicopathological characteristics and overall survival in patients with renal cell carcinoma

Purpose: There is a need for identifying molecular prognostic biomarkers to better predict clinical outcomes in patients with renal cell carcinoma (RCC). This study investigated the pattern of cyclin D1 and p57 expression in RCC patients and evaluated their relation with clinicopathological characteristics and overall survival (OS). Methods: Immunohistochemistry was applied to paraffin-embedded tissue sections of 74 RCC patients. Two cut-off groups were defined by the fraction of positive cells as fol-lows: ≤10% and >10% positive cells for cyclin D1, and ≤5% and >5% positive cells for p57. Results: Cyclin D1 expression in >10% of positive cells was observed mostly in the clear cell RCC, while p57 expression in ≤5% of positive cells was found in 86% of chromophobe RCC specimens. The higher expression of cyclin D1 and lower expression of p57 were more frequent in grade I-II tumors. OS was associated with unfavorable clinicopathological characteristics. However, cyclin D1/p57 expression did not influence the survival rates. Conclusion: Although cyclin D1 and p57 expression did not affect survival rates in RCC patients, proper validation and establishment of the qualitative cut-off point are needed for these tumors

Immunohistochemical analysis of cyclin A expression in Wilms tumor

Background: Cyclin A overexpression is found in a variety of human tumors and correlates with unfavorable outcome. We analyzed immunohistochemical expression of cyclin A in Wilms tumor (WT) in relation to clinicopathological characteristics, preoperative chemotherapy (PrOpChTh), and overall survival (OS). Methods: This retrospective study involved 43 patients who underwent nephrectomy from January 1996 to October 2010. Tumor stage and histological subtype were determined by revised Societé International d’Oncologie Pediatrique protocol, based on histological components/alterations caused by PrOpChTh, within the prognostic group of low, intermediate and high risk, and with criteria for anaplasia. The regressive/necrotic changes in total tumor mass of primary tumor and the proportion of epithelial, blastemal, and stromal components in the remaining viable tumor tissue were also determined. Cyclin A expression was evaluated by immunohistochemistry using a polyclonal rabbit, antihuman antibody (H-432). Results: Cyclin A overexpression was found in 34.3% of WTs, with higher frequency in tumors with epithelial (31.3%) and blastemal (37.1%) components than those with stromal component (17.7%). Regarding histological type, cyclin A overexpression was found most often in focal anaplasia (100%), stromal (60%), and diffuse anaplastic (66.7) WTs. The overexpression was also more frequent in stages 3 and 4 (77.8% and 66.7%, respectively) compared to tumors in stages 1 and 2 (13.3% and 12.5%, respectively; p = 0.004) in all components, as well as in blastemal component in stages 3 and 4 (77.8% and 66.7%, respectively) vs. stages 1 and 2 (13.3% and 25%, respectively, p = 0.009). Cyclin A overexpression in all components was 66.7% in WTs with metastasis and 31.3% in WTs without metastasis (p = 0.265, Fisher test). Log-rank testing revealed differences of OS regarding stage (p = 0.000), prognostic groups (p = 0.001), and cyclin A expression in blastemal component (p = 0.025). After univariate analysis, tumor stage (p = 0.001), prognostic group (p = 0.004), and cyclin A expression in blastemal component (p = 0.042) were significant prognostic factors for OS; however, after multivariate analysis, none of these factors were confirmed as independent predictors of survival. Discussion: This study showed that cyclin A overexpression might be associated with the development and progression of WT with anaplasia. Also, cyclin A overexpression was more often observed in advanced stages (3 and 4) of WT, in the group of high-risk WTs, and in focal and diffuse anaplasia WTs. There was no relation of cyclin A overexpression and metastatic ability of WT. Although this study has not confirmed the prognostic value of cyclin A overexpression, its association with unfavorable prognosis should be further evaluated. Copyright 2019 Radojevic-Škodric et al