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EN
Introduction: Invasive lobular carcinoma (ILC) occurs in 5–15% of all cases of breast cancer. In most studies, it is found to be more common among older patients, form larger tumours and present with ill-defined margins, in comparison to invasive ductal carcinoma (IDC). Material and methods: Histological preparations were obtained from 651 patients suffering from breast cancer. Preparations stained with hematoxylin and eosin were used to identify tumour type and grading. Samples underwent a basic molecular profile evaluation encompassing ER (oestrogen receptor), PR (progesterone receptor) and human epidermal growth factor receptor 2 (HER2) expression. Results: 592 cases of IDC and 59 cases of ILC were detected. The median age was 60 in both groups. While there were no statistically significant differences between IDC and ILC in nodal status and tumour size for all age groups, IDC was more frequently diagnosed at higher grading (G3). G3 accounted for 32% of all IDC specimens compared to only 13% of ILC specimens. In both groups, the most prevalent combination of hormone receptors was ER+/PR+/HER2-. The differences in ER and PR expression were statistically significant; both were assessed as positive in most ILC cases and just over half of IDC. No HER2 amplification was noted in most cases in both cancer subtypes. Conclusions: In our study, IDC and ILC showed no difference with respect to patients’ median age at the diagnosis and local disease advancement defined by TNM. ILC cases were hormone-dependent and HER2-negative more frequently than IDC. Grade 3 tumours accounted for a higher proportion of IDC cases. This was in line with several other clinicopathological analyses of breast cancer. However, there are also several papers indicating ILC’s association with favourable prognostic features, not only in terms of hormone receptors and HER2 expression but also tumour size and nodal involvement. This underlines the fact that clear differences between IDC and ILC prognosis still cannot be established.
EN
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.
EN
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.
OncoReview
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2021
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vol. 11
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issue 4
95-101
EN
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.
EN
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.
EN
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.
EN
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.
PL
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.
EN
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.
EN
The risk of carcinoma increases in patients with a 10-year or longer duration of ulcerative colitis (UC). To search for a more objective parameter to assess epithelial dysplasia. The study comprised 25 cases of longstanding UC: 7 cases with regenerative atypia, 7 with low grade dysplasia, 7 with high grade dysplasia, and 4 cases indefinite for dysplasia. The colonic biopsies obtained during endoscopy were stained with H&E to identify the aforementioned categories. Seventy-five sections from biopsy specimens were stained immunohistochemically to detect differences in the frequency and pattern of nuclei positive for the proliferation marker Ki67 and p53. In high grade dysplasia, the distribution of Ki67 positive cells was diffuse throughout the full length of the crypt, whereas low grade dysplasia and epithelium indefinite for dysplasia, as well as regenerative epithelium, showed an expanded basal zone. None of the regenerative atypia cases showed strong intensity p53 staining compared to dysplasia cases. None of the high grade dysplasia cases showed restricted p53 staining to the lower two thirds of the crypt. All the cases of HGD showed extension of Ki67 and p53 staining above the basal two thirds of the crypt. Ki67 and p53 immunostained cell assessment combined with routine histological evaluation of colorectal mucosa can improve the diagnostic accuracy, as well as the assessment of malignant transformation risk.
EN
We present a case of 44-year old women with two primary carcinomas diagnosed in one breast. The carcinomas were invasive mixed ductal-lobular and lobular invasive carcinoma. This specific case was difficult to treat because these carcinomas are differentially susceptible to hormonal treatment. We refrained from making therapeutic decisions based solely on characteristics of the first primary would be improper because important therapeutic option (hormonal treatment) would not be used to treat the other primary. Therefore, the treatment would have been suboptimal. In our opinion, this case supports the close examination of biological characteristics of each carcinoma focus, especially if greater than one cancer focus with different morphology exists in the breast tissue.
EN
Intrauterine Parvovirus B19 infections may cause fetal anemia, non-immune hydrops fetalis or abortion. This study focuses on the pathogenic role of Parvovirus B19 in non-immune hydrops fetalis at Hacettepe University, a major reference hospital in Turkey. Twenty-two cases of non-immune hydrops fetalis were retrospectively selected out of a total of 431 hydrops fetalis specimens from the Department of Pathology archieves. Paraffine embedded tissue sections from placental and liver tissues from each case were evaluated by histopathology, immunohistochemistry, nested PCR and commercial quantitative Real-time PCR. Viral DNA was detected in placental tissues by Real-time PCR in 2 cases (2/22, 9.1%) where histopathology also revealed changes suggestive of Parvovirus B19 infection. No significant histopathologic changes were observed for the remaining sections. Nested PCR that targets the VP1 region of the viral genome and immunohistochemistry for viral capsid antigens were negative for all cases. As a result, Parvovirus B19 is identified as the etiologic agent for the development of non-immune hydrops fetalis for 9.1% of the cases in Hacettepe University, Turkey. Real-time PCR is observed to be an effective diagnostic tool for nucleic acid detection from paraffine embedded tissues. Part of this study was presented as a poster at XIIIth International Congress of Virology, San Francisco, USA (Abstract V-572).
EN
Duodenal injuries, though rare, carry high rates of morbidity and mortality. The aim of the study was to evaluate the healing of the duodenal wall with the use of a Small Intestinal Submucosa (SIS) patch. Material and methods. We studied 40 Whistar-Albino rats divided into two groups. In group A, we created a small defect in the duodenal wall, which was immediately covered with a SIS patch. In group B, the SIS patch was sutured over the defect after 6-8 hours, in order to induce peritonitis. The animals of both groups were sacrificed after 2, 6, 12 and 16 weeks respectively. In addition, we studied the immunohistochemical expression of TGF-β, which is a major constituent of SIS, and plays a central role in the healing process. Results. Histology showed progressive development of the layers of the duodenal wall over the patch as early as the 2nd week in some of the animals of group A. Mucosa developed later on in the animals of group B, presumably due to the more intense inflammation elicited by peritonitis. Expression of TGF-β was initially more pronounced in the epithelial cells of the regenerating mucosa of animals of group A, but it was maintained in higher levels in the animals of group B, which showed delayed mucosa degeneration. Conclusions. SIS appears to be both efficient and safe for the management of duodenal trauma. TGF-β seems to play an important role in the healing process, inducing regeneration of the stroma, and controling epithelial growth.
EN
Glioblastoma (GBM, WHO grade IV) is the most lethal type of brain tumours. Despite advances in radiotherapy, chemotherapy and surgical techniques, this tumour is still associated with a median overall survival of approxi­mately 1 year. Histopathological features of GBM include nuclear atypia, foci of palisading necrosis, microvas­cular proliferation and robust mitotic activity. Glioblastoma is one of the best vascularized tumours in humans and its proliferation is hallmarked by a distinct proliferative vascular component. Studies of glioblastoma’s vas­cularization have cast some light on the role of non-endothelial cells in tumour neoangiogenesis. A characteristic feature of protein CD133 is its rapid down-regulation during cell differentiation, which makes it a unique cell sur­face marker for identification of stem cells in brain tissue. CD133+ tumour cells are located mainly in perivascular niches. CD133 positive cells were also found in blood vessels wall. The aim of this study was to optimize immu­nohistochemical staining method to facilitate identification of cells recognized by anti-CD133 antibody in paraf­fin-embedded glioblastoma tissue sections. In this study, several pretreatments, detection systems, dilution of an­tibody and time incubation were used. Immunohistochemical staining method in which autoclave, a buffer pH 9.0 and LSAB+System-HRP were used gave the best result.
PL
Najczęstszym i jednocześnie najgorzej rokującym nowotworem pochodzenia astrocytarnego jest glioblastoma (IV stopień złośliwości według Światowej Organizacji Zdrowia). Obraz mikroskopowy glioblastoma charaktery­zuje się atypią komórkową, obecnością ognisk martwicy palisadowej oraz proliferacją drobnych naczyń. Wyróżniamy dwa typy glioblastoma: pierwotny i wtórny. Jedną z podstawowych cech histopatologicznych tego nowotworu jest obecność proliferacji naczyniowych. Proliferacje naczyń glioblastoma rozpoznawane są jako wielowar­stwowe kłębki rozrośniętych i mitotycznie aktywnych komórek endotelialnych. Komórki macierzyste odgrywa­ją znaczącą rolę w tworzeniu sieci naczyń krwionośnych nowotworu za sprawą różnicowania w kierunku ko­mórek endotelialnych. Za marker nowotworowych komórek macierzystych uważa się antygen CD133. Komórki nowotworu wykazujące ekspresję tego białka rozpoznawanego przez odpowiednie przeciwciała zlokalizowane są w niszach otaczających naczynia krwionośne występujące w masie nowotworu. Komórki CD133+ występują również w ścianach naczyń krwionośnych. Celem przeprowadzonych badań było opracowanie optymalnej im­munohistochemicznej metody barwienia, z wykorzystaniem przeciwciała przeciw CD133, która ułatwi identyfi­kację komórek macierzystych. Materiał do badań stanowiły preparaty histopatologiczne pobrane do rutynowych badań histopatologicznych w czasie zabiegu operacyjnego z wcześniej rozpoznanymi przypadkami glioblastoma. Badania obejmowały różne metody barwień immunohistochemicznych z wykorzystaniem zróżnicowanych spo­sobów odmaskowywania antygenów, z zastosowaniem odmiennych buforów, systemów detekcyjnych oraz roz­cieńczeń przeciwciała i czasów inkubacji preparatów z przeciwciałem. Najlepsze wyniki barwienia immunohisto­chemicznego otrzymano w preparatach, w których w celu odmaskowywania antygenu zastosowano autoklaw, bufor o pH 9,0 i system detekcyjny LSAB+System-HRP.
EN
HER-2/neu overexpression is considered an important prognostic factor, which may predict an aggressive clinical course of several tumours, including cervical cancer. Material and method: HER-2/neu expression was assessed by immunohistochemical technique in 298 patients with stage IB and IIA cervical cancer, of either planoepithelial or adenomatous type. HER-2/neu expression was compared in groups of patients selected based on generally accepted prognostic factors, e.g. clinical stage, histological type, presence of metastases to regional lymph nodes, invasion of vascular space and degree of radiation-induced destruction of tumor. Using the Cox model, a multivariate analysis of effect of selected prognostic factors was performed, both in relation to overall survival and to symptom-free survival. Results: Positive reaction to HER-2/neu was obtained in 135 cases (45.3%); the reaction was pronounced (3+) in 23 cases (7.8%) and moderate (2+) in 41 cases (13.7%). No positive reaction was obtained in 163 cases (54.7%). Analysis of survival yielded the following results: probability of 5-year overall survival for the entire patient population was 90.9% and that of 10 years – 85.2%. Overall survival curve for the entire study population is presented. Recurrence-free 5- and 10-year survival rates were 83.3% and 82.3%, respectively. Symptom-free 5- and 10-year survival rates were significantly influenced by: lymph node involvement and their number, invasion of vascular space, histological type and HER-2/neu expression. Cox analysis demonstrated a significant correlation between risk of recurrence or death and the following factors: lymph node metastases and their number, invasion of vascular space, histological type of tumour and HER-2/neu expression. The risk of recurrence or death with a single nodal metastasis and several nodal metastases is 2.4- and 5.1-fold greater than when no nodal metastases are present. The fact of vascular space involvement results in a 3-fold increase of risk of recurrence or death. In the case of planoepithelial cancer, the risk of recurrence or death is 0.4-fold that for adenomatous cancer. Finding of a strong HER-2/neu expression (2+, 3+) increases 2.7-fold the risk of therapeutic failure. Conclusions: No statistically significant differences were found in the HER-2/neu expression in groups of patients defined based on clinical-pathological parameters (i.e. clinical stage, histological type, regional lymph node metastases, radiation-induced cervix sterilization). The following prognostic factors had a significant impact on symptom-free survival: histological type, presence and numbers of lymph node metastases, invasion of vascular space, as well as TP53, BCL2 and HER-2/neu expression. Among all factors analysed, most significant prognostic impact, both in terms of overall survival and symptom-free survival, was associated with involvement of pelvic lymph nodes.
PL
Nadekspresja HER-2/neu uważana jest za istotny czynnik prognostyczny mogący wskazywać na agresywny przebieg kliniczny wielu nowotworów, w tym RSM. Materiał i metody: Posługując się metodą immunohistoche-miczną, przeprowadzono ocenę ekspresji HER-2/neu u 298 chorych leczonych z powodu RSM w stopniach IB i IIA zarówno w grupie chorych na raka płaskonabłonkowego, jak i gruczołowego. Dokonano porównania ekspresji HER-2/neu w grupach chorych wyróżnionych na podstawie uznanych czynników prognostycznych, takich jak stopień klinicznego zaawansowania, typ histologiczny, obecność przerzutów do regionalnych węzłów chłonnych, zajęcie przestrzeni naczyniowej i stopień uszkodzenia popromiennego nowotworu. Posługując się modelem Coksa, przeprowadzono wielowariantową analizę wpływu ocenianych czynników prognostycznych zarówno na przeżycia całkowite, jak i bezobjawowe. Wyniki: Pozytywną reakcję na HER-2/neu stwierdzono w 135 przypadkach (45,3%): w 23 przypadkach była to reakcja o dużym nasileniu - 3+ (7,8%), a w 41 przypadkach o nasileniu średniego stopnia - 2+ (13,7%). W 163 przypadkach (54,7%) nie stwierdzono pozytywnej reakcji. Wyniki analizy przeżyć są następujące: prawdopodobieństwo całkowitego przeżycia 5 lat dla całej grupy chorych wyniosło 90,9%, a 10 lat - 85,2%. Przedstawiono krzywą przeżycia całkowitego analizowanej grupy chorych. Prawdopodobieństwo przeżycia bez nawrotu choroby 5 i 10 lat wyniosło odpowiednio 83,3% i 82,3%. Istotny wpływ na 5- i 10-letnie przeżycia bezobjawowe miały: przerzuty do węzłów chłonnych i ich liczba, zajęcie przestrzeni naczyniowej, typ histologiczny i ekspresja HER-2/neu. W wyniku przeprowadzonej analizy Coksa wykazano istotny wpływ prognostyczny na ryzyko nawrotu lub zgonu takich czynników, jak: przerzuty do węzłów chłonnych i ilość zajętych węzłów, zajęcie przestrzeni naczyniowej, typ histologiczny i ekspresja HER-2/neu. Ryzyko nawrotu lub zgonu dla jednego zajętego węzła oraz dla większej liczby zajętych węzłów chłonnych jest 2,4 oraz 5,1 razy wyższe od odpowiedniego ryzyka dla węzłów niezajętych. Fakt zajęcia przestrzeni naczyniowej zwiększa niemal 3-krotnie ryzyko nawrotu lub zgonu. Dla raka płaskonabłon-kowego ryzyko nawrotu lub zgonu stanowi 0,4 ryzyka niepowodzenia dla raka gruczołowego. Stwierdzenie silnej ekspresji HER-2/neu (2+, 3+) zwiększa 2,7 razy ryzyko niepowodzenia leczenia. Wnioski: Nie stwierdzono istotnych statystycznie różnic w ekspresji HER-2/neu w grupach chorych wyróżnionych na podstawie parametrów kliniczno-patologicznych (tj.: stopnia klinicznego zaawansowania, typu histologicznego, przerzutów do regionalnych węzłów chłonnych i popromiennej sterylizacji szyjki macicy). Istotny wpływ statystyczny na przeżycia bezobjawowe miały następujące czynniki prognostyczne: typ histologiczny, przerzuty do węzłów chłonnych i ich liczba, inwazja przestrzeni naczyniowej oraz ekspresja TP53, BCL2 i HER-2/neu. Spośród wszystkich analizowanych czynników największy wpływ prognostyczny zarówno na przeżycia całkowite, jak i bezobjawowe miała obecność przerzutów do węzłów chłonnych miednicy.
PL
Lymphomatoid papulosis (LyP) jest rzadką chorobą skóry, najczęściej obserwowaną u dorosłych, a jej występowanie w populacji pediatrycznej jest niezwykle rzadkie. W pracy przedstawiono przypadek 6-letniego dziecka płci męskiej, u którego stwierdzono cechy kliniczne i histopatologiczne zgodne z rozpoznaniem LyP. Na skórze pacjenta obserwowano liczne rumieniowe grudki zlokalizowane na tułowiu i kończynach, a towarzyszył im łagodny świąd. Zmiany chorobowe pojawiały się nawrotowo, następnie ustępowały i zmieniały morfologię. W badaniu przedmiotowym nie stwierdzono limfadenopatii ani objawów ogólnoustrojowych. W badaniu histopatologicznym w skórze właściwej stwierdzono gęsty naciek limfocytów atypowych z hiperchromatycznymi i nieregularnymi jądrami komórkowymi. Analiza immunohistochemiczna potwierdziła ekspresję CD30 w naciekających komórkach, co potwierdza rozpoznanie LyP. W celu złagodzenia świądu i stanu zapalnego podawano miejscowo glikokortykosteroidy, chociaż uzyskano jedynie minimalne złagodzenie objawów. Korzystne efekty fototerapii wąskopasmowej UVB 311 obserwowano przez cztery miesiące. Niemniej jednak po zaprzestaniu leczenia zaobserwowano ponowne pojawienie się zarówno zmian guzkowych, jak i mniejszych zmian grudkowych. W związku z tym rozpoczęto schemat terapeutyczny polegający na podawaniu metotreksatu w dawce 10 mg raz na tydzień. Leczenie LyP różni się zależnie od ciężkości zmian i objawów u pacjenta. Decyzje dotyczące leczenia należy dokładnie rozważyć ze względu na stosunkowo łagodny charakter choroby. Rozpoznanie LyP u dzieci i młodzieży stanowi wyzwanie ze względu na rzadkość występowania choroby i możliwość błędnego rozpoznania tej jednostki chorobowej z chłoniakami złośliwymi. Histopatologia i immunohistochemia odgrywają kluczową rolę w odróżnianiu LyP od bardziej agresywnych jednostek chorobowych.
EN
Lymphomatoid papulosis (LyP) is a rare cutaneous disorder, most commonly observed in adults, and its occurrence in the pediatric population is exceedingly rare. We present the case of an 6-year-old male patient who exhibited clinical and histopathological features consistent with LyP. The patient presented with multiple erythematous papules on the trunk and extremities, which were accompanied by mild pruritus. The lesions intermittently appeared, disappeared, and changed in morphology. No lymphadenopathy or systemic symptoms were noted. The histopathological examination revealed a dense infiltrate of atypical lymphocytes with cerebriform nuclei in the dermis. Immunohistochemical analysis confirmed CD30 expression in the infiltrating cells, supporting the diagnosis of LyP. Topical corticosteroids were administered to alleviate pruritus and inflammation, although only minimal symptomatic relief was achieved. The beneficial effects of narrowband ultraviolet B (UVB) 311 phototherapy were observed for a duration of four months. Nevertheless, following the cessation of treatment, the reappearance of both the nodular lesions and smaller papular lesions was observed. Consequently, a therapeutic regimen consisting of the administration of methotrexate at a dosage of 10 mg once per week was initiated. The treatment of LyP varies depending on the severity of the lesions and the patient’s symptoms, treatment decisions need to be carefully weighed due to the relatively benign nature of the disease. The diagnosis of LyP in pediatric patients is challenging because of its rarity and potential confusion with malignant lymphomas. Histopathology and immunohistochemistry play a pivotal role in distinguishing LyP from more aggressive entities.
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