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Content available Primary breast angiosarcoma – a case report
Introduction. Angiosarcoma is a rare breast cancer that can be primary or secondary after surgery or after breast cancer radiotherapy. It is important that breast angiosarcoma belongs to tumors with a non-specific clinical and radiological picture. Aim. The study of the biopsies contained aggressive vasomotor hyperplasia. Description of the case. The presented case concerns the primary angiosarcoma of the right breast in a 56-year-old woman who had never had a surgical procedure before, nor radiotherapy in the area of the breast. Conclusion. Histopathological examination supported by immunohistochemistry is a reliable and indispensable diagnostic element in the diagnosis of vascular sarcoma.
Background: Colorectal cancer (CRC) is one of the most common malignancies in the world. The cancer stem cell (CSC) markers are associated with aggressive cancer types and poor prognosis. The objective of the study was to evaluate the CD133 expression and to correlate it with clinicopathological features in patients with CRC. Material and Methods: Our study included ninety patients with CRC who underwent curative surgical resection from 2012 to 2017 at the University Clinic for Digestive Surgery, Skopje, North Macedonia. Tumor samples were first analyzed with standard histopathological methods and then the CD133 expression was investigated immunohistochemically. The level of expression of CD133 was classified semiquantitatively. Low positivity was defined as positive immunoreactivity in <50% of tumor glands, and high positivity was defined as positive immunoreactivity in ≥50% of tumor glands. Furthermore, clinicopathological features of patients were retrospectively reviewed. Results: High expression of CD133 was found in 47.8% of patients’ CRC samples. In 69.6% of patients with metastatic lesions in visceral organs we found high expression of CD133. We found statistically significant differences in the expression of CD133 between patients with and without visceral metastatic lesions (P = 0.0153), between patients with a different T category (P = 0.0119), N status (P = 0.0066) and grade (G) (P = 0.0115). Our results showed that the stage of disease has the greatest impact on expression of CD133 (P < 0.00001). Conclusion: High expression of CD133 is a useful marker for prediction of the clinically aggressive type of CRC and can be routinely implemented in standard pathohistological diagnostics.
Purpose: To evaluate chosen mucins (mucin 1, 4, 5AC) expression in pancreatic intraepithelial neoplasia, which is a precursor lesion of pancreatic ductal adenocarcinoma. Materials and methods: The study group included 70 patients operated on due to inflammation, cysts and pancreatic ductal adenocarcinoma with pancreatic intraepithelial neoplasia revealed additionally. Mucin 1, 4 and 5AC expression was assessed by immunohistochemical method using polyclonal antibodies. Results: Statistical analysis proved a positive correlation between the expression of mucin 1, 4 and 5AC proteins and the presence and staging of pancreatic intraepithelial neoplasia (p<0.001). Statistically significant correlations were determined between mucin 1, 4 and 5AC and the location of PanIN lesion in the pancreas. Positive correlations were found between mucin 5AC expression and the type of a basic disease (p=0.014). Differences in the expression of MUC 1, 4 and 5AC proteins between healthy pancreatic ducts and various stages of pancreatic intraepithelial neoplasia were statistically significant (p<0.001). Conclusions: Overexpression of mucin 1, 4 and 5AC is related to the presence of pancreatic intraepithelial neoplasia. This suggests that overproduction of mucus is a phenomenon occurring early in the process of carcinogenesis in the pancreas and has its beginning in precancerous lesions of an early stage.
We aimed to investigate the correlation between quantitative CerbB-2 expressions with conventional prognostic factors, and distinct nodal involvement in patients with invasive breast carcinoma. One hundred fifty seven consecutive breast carcinoma patients were retrospectively analysed. Level I–II, Level III, and Rotter (Interpectoral) group lymph nodes were separately examined and recorded. For each patient estrogen receptor (ER), progesteron receptor (PR), CerbB-2, P53 status were defined using immunohistochemistry. Age, tumor localisation, menopausal status, grade and the presence of intraductal component were also recorded. CerbB-2 expression did not correlate with age, localisation and menopausal status. There was a reverse, but weak correlation with tumor size and CerbB-2 expression (p=0.034). In subgroup analysis of CerbB-2 positive cases, the magnitude of CerbB-2 positivity did not correlate with tumor size (p=0.551). In univariate analysis CerbB-2 expression did not correlate with nodal involvement in Level I-II, and Rotter. In subgroup analysis of patients with positive CerbB-2, positivity of CerbB-2 linearly increased with the number of positive lymph nodes in Level I-II, and this difference was significant (p=0,039). There was a significant correlation between CerbB-2 expression and Level III nodal metastases (p=0.005). But this correlation was not significant among CerbB-2 positive patients (p=0.82). P53, PR positivity and the presence of intraductal component did not differ according to oncogene expression. We detected a reverse correlation with ER positivity and CerbB-2 positivity (p=0.011). It is concluded that quantitative expression of CerbB2 positivity increases with nodal involvement in Level I–II axillary lymph nodes, and ER. Also, CerbB-2 positivity is more common among patients with Level III lymph node metastases.
Content available remote Neointima Contribution to Haemostasis of Polyester Vascular Grafts
The aim of the study. Assessment of dynamic changes in the expression of activators and inhibitors of coagulation and fibrinolysis in the neointima of polyester vascular grafts during their healing process.Material and methods. The study was carried out on 18 dogs that underwent replacement of infrarenal abdominal aorta with a polyester DALLON - double velour prosthesis. Grafts were removed after 1, 4 and 12 months and fixed according to the AMeX method. Immunohistochemical labeling for tissue factor (TF), tissue factor pathway inhibitor (TFPI), tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), plasminogen activator inhibitor type-1 (PAI-1), prothrombin activation fragment F1+2 (F1+2) and D-dimer (DD) was performed on the neointima of the grafts.Results. TF expression did not demonstrate any significant differences in all study periods. TFPI expression appeared at 4 months and was increased at 12 months. Intensive F1+2 expression was shown at 1 month; its mild expression was still present in the following periods of the study. Plasminogen activators were demonstrated at 1 month and their expression was increased at 4 and 12 months, whereas weak expression of PAI-1 and DD was shown in all study periods.Conclusions. High thrombotic potential of polyester vascular graft neointima is present in all periods of the graft healing process. Increasing TFPI and plasminogen activators expression in the late postoperative follow-up favors graft patency maintenance.
The detection of micrometastases in patients with operable non-small cell lung carcinoma (NSCLC) could have a considerable influence on the choice of a proper treatment.The aim of the study was to evaluate the usefulness of microscopic examination and immunohistochemistry for the detection of micrometastases or single malignant cells in the bone marrow of patients undergoing surgery for NSCLC, as their late survival and recurrence-free time is dependent on immunohistochemical markers of cancer metastases in the bone marrow.Material and methods. Thirty-five patients were included in the study. Their age range was from 47 to 78 years old. Bone marrow was obtained from a rib during surgery for lung cancer. Both a resected tumour and bone marrow sample were tested for the presence of cytokeratins AE1/AE3, CAM 5.2, CK-7, and CK-18 and other indicators such as CD31 and CD34. The mean time of observation was 871.6 days.Results. Microscopic examination detected no malignant cells or micrometastases in the bone marrow in the analyzed group. Cytokeratin CAM 5.2 was detected in 33 cases (94.23%) in a lung tumour and in 21 cases (60%) in the bone marrow. Statistical analysis (chi2 NW), showed a statistically significant relationship between the presence of CAM 5.2 expression in a tumour and in the bone marrow. In all analysed cases, the expression of cytokeratin AE1/AE2 was found in a tumour, but was not detected in any bone marrow sample. Cytokeratin CK-7 and CK-18 were present in a tumour in 20 (57.14%) and 23 (65.71%) patients, respectively. In the bone marrow, the expression of cytokeratin CK-7 was found in one case (2.86%), and CK-18 was not found in any patients. Thirteen (37.14%) patients died during follow-up. Local recurrence was diagnosed in three patients (8.57%) and distant metastases in 15 patients (42.86%). Mean recurrence-free time was 687.7 days.Conclusions. On the basis of immunohistological tests, it was shown that a significant correlation existed between the presence of cytokeratin CAM 5.2 expression in a tumour and in the bone marrow. Its presence in the bone marrow was a good predictive factor for recurrence-free time. Mortality and the frequency of locoregional recurrence and distant metastases depend on pathological lung cancer staging.
Although the widespread of early screening and advanced medical therapies, the breast cancer incidence rate continues to rise among Algerian women. This retrospective study investigated mammary lesions’ epidemiological profile and histopathological characteristics and evaluated primary invasive breast cancer prognostic factors. We found that the incidence of breast cancer increases in middle- aged women between 40 and 60 years. Scarff Bloom Richardson grade II predominates in invasive breast cancer samples. In this study, molecular profiling shows that 82.1% of invasive tumours are hormone receptor-positive. A significant correlation is observed between the age of the patient and the SBR grade (p = 0.001) and with the hormone receptor expression (p = 0.001). In addition, the tumour grade is significantly correlated to oestrogen and progesterone receptor expression (p = 0.000; p = 0.000, respectively). Twenty-two per cent of cases were human epidermal growth factor receptor 2-positive. The Ki-67 proliferation index is expressed in 91% of breast cancer patients and was significantly associated with Scarff Bloom Richardson grade (p = 0.030), the progesterone receptor expression (p = 0.029) and with human epidermal growth factor receptor 2-positivity (p = 0.023). Primary breast cancer with a high grade is more frequent (31%) in young women under 40 years old, presenting 17% of our population. In summary, breast cancer patients in Algeria develop an unfavourable profile. Immunohistochemistry assay has played a pivotal role in assessing breast cancer predictive biomarkers improving the tumour behaviour and response to treatment.
Content available remote Molecular screening for hereditary nonpolyposis colorectal cancer in Bulgaria
Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease, caused by germline mutations in DNA mismatch-repair genes (MMR). These mutations lead to microsatellite instability (MSI). It has been found that the MSI is not confined to the setting of hereditary disease and may be seen in approximately 12-17% of the sporadic CRCs. In 1998 a National Registry for CRC was instituted in Queen Giovanna Hospital, Sofia. A total of 150 patients have been selected for MSI analysis and 25 tumors showed to be unstable, 14 with loss of heterozygosity (LOH). These tumors were further analyzed for MLH1 promoter hypermethylation and a significant association between this epigenetic change and MSI/LOH sporadic cases. We proposed this method as a step that follows the analysis for MSI and prior to the screening for MMR mutations. The mutation screening detected four known and two novel mutations, one unpublished and four known intronic polymorphisms in both hMLH1 and hMSH2 genes. The use of IHC analysis has been found effective in the investigation of some unclear molecular variations. We developed an efficient diagnostic strategy for HNPCC testing and the mutation status of 80% MSI HNPCC cases could be detected.
Background: Tumor hypoxia is an adverse prognostic factor which promotes cancer aggressiveness and limits its radio- and chemosensitivity. The aim of our study was to explore the relationship between endogenous hypoxia markers and classic prognostic factors, including clinical stage and the expression of ER, PR, and HER2 in primary untreated breast carcinoma. Methods: A retrospective immunohistochemical analysis of archived tissue blocks collected from 153 women, who underwent total mastectomy and lymph node dissection, included the expression of two hypoxia-related proteins: HIF-1α and GLUT1. Results: GLUT1 labelling index (LI) showed a positive correlation with T stage (R = 0.18, p = 0.026) and HER2 status (R = 0.25, p = 0.002), and a negative correlation with the expression of ER (R = −0.19, p = 0.017) and PR (R = −0.17, p = 0.032). HIF-1α LI showed a positive correlation with ER expression (R = 0.16, p = 0.045). In the multivariate regression analysis, a different relationship between classic prognostic factors and the two tested hypoxia proteins was proven. Higher GLUT1 expression correlated with ER and PR negativity (p = 0.02 and p = 0.01, respectively) as well as with higher expression of HER2 (p = 0.04). HIF-1α showed no association with PR and HER2, but a positive correlation with ER (p = 0.02). Neither of the hypoxia proteins was associated with a tumor grade. Only one clinical feature, T stage, correlated with both of the hypoxia markers: positively with GLUT1 (p = 0.049) and negatively with HIF-1α (p = 0.01) expression. Conclusions: In breast cancer, GLUT1 expression may be considered an additional prognostic factor which correlates with an adverse status of HER2 and hormonal receptors, and indicates a more hypoxic, radio- and chemotherapy refractory profile of carcinoma.
Tło: Hipoksja w  guzie nowotworowym stanowi niekorzystny czynnik prognostyczny, ogranicza jego promienioi chemiowrażliwość oraz promuje bardziej agresywny przebieg choroby. Przewidywanie rokowania i odpowiedzi na leczenie wymaga wiedzy o związku hipoksji z uznanymi czynnikami prognostycznymi. Celem badania było określenie zależności pomiędzy endogennymi markerami hipoksji w  pierwotnym przewodowym raku piersi a  klasycznymi czynnikami prognostycznymi, takimi jak stopień zaawansowania klinicznego oraz ekspresja receptorów ER, PR i HER2. Metody: Retrospektywna analiza immunohistochemiczna archiwizowanych bloczków tkanek pobranych od 153 kobiet, poddanych mastektomii i limfadenektomii pachowej, objęła ekspresję dwóch związanych z hipoksją białek: HIF-1α i GLUT1. Wyniki: Indeks wiązania GLUT1 (GLUT1 LI) wykazał korelację dodatnią z wielkością guza (R = 0,18, p = 0,026) i ekspresją HER2 (R = 0,25, p = 0,002) oraz ujemną z ekspresją ER (R = −0,19, p = 0,017) i PR (R = −0,17, p = 0,032). HIF-1α LI korelował wyłącznie z ekspresją ER (R = 0,16, p = 0,045). W analizie wieloczynnikowej wykazano zróżnicowaną zależność pomiędzy klasycznymi czynnikami prognostycznymi i testowanymi markerami hipoksji. GLUT1 LI korelował negatywnie z ekspresją ER i PR (odpowiednio p = 0,02 i p = 0,01) oraz pozytywnie z ekspresją HER2 (p = 0,04). Nie udowodniono korelacji pomiędzy HIF-1α LI a ekspresją PR czy HER2, natomiast wykazano jego dodatnią zależność z ekspresją ER (p = 0,02). Żaden marker hipoksji nie korelował ze stopniem zróżnicowania histologicznego nowotworu. Tylko jeden kliniczny czynnik – wielkość guza (T) – korelował z ekspresją badanych białek: dodatnio z GLUT1 (p = 0,049), a ujemnie z HIF-1α (p = 0,01). Wnioski: Ekspresja GLUT1 w raku piersi może stanowić dodatkowy czynnik prognostyczny, korelujący z niekorzystnym statusem receptora HER2 i receptorów hormonalnych oraz wskazywać na bardziej hipoksyczny, oporny na radioi chemioterapię, profil raka.
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