E-cadherin adhesion molecule and syndecan-1 expression in various thyroid pathologies

Cadherins and syndecans are transmembrane glycoproteins implicated in cell-cell and cell-matrix adhesion. Impairment of cadherin and syndecan mediated adhesion is likely to constitute one of the main factors leading to the reduced cell-cell and cell-matrix adhesion characteristics of tumor cells and play a pivotal role in the acquisition of invasive and metastatic proprieties by neoplastic epithelial cells. Aim: To elucidate the role and alterations of syndecan-1 expression in comparison with those of E-cadherin in normal and pathological thyroid glands (TG). Methods: A total of 55 TG carcinomas, 40 TG adenomas, 40 cases of hyperplastic TG disorders and 20 cases of normal TG autopsy samples, were evaluated by immunohistochemistry. The staining intensity, and localization of syndecan-1 and E-cadherin in sequential sections were examined, and semi-quantified. Results: Immunostaining of syndecan-1 and E-cadherin was strong in normal follicular TG epithelial cells, and located mainly in basolateral membrane. No significant change was seen in either molecule in hyperplastic TG disorders compared with TG adenomas. A significant reduction in expression of both syndecan-1 and E-cadherin was seen in well-differentiated TG carcinomas as compared with normal TG epithelium (p = 0.0001 and p = 0.032, respectively). Similarly, there was a significant reduction of both molecules expression in poorly differentiated and anaplastic TG carcinomas compared to well differentiated tumors (syndecan-1: p = 0.0037; and E-cadherin: p = 0.075). Conclusion: Decreased E-cadherin and syndecan-1 expression along with decreasing cellular differentiation may be involved in the complex mechanism of progression of TG pathology.Кадгерины и синдеканы — это трансмембранные гликопротеины, участвующие в межклеточной адгезии и адгезии клеток к матриксу. Изменения экспрессии этих молекул играют главную роль в приобретении инвазивного и метастатического потенциала злокачественно трансформированными эпителиальными клетками. Цель: оценка роли экспрессии синдекана-1 и Е-кадгерина в ткани щитовидной железы в норме и при патологии. Методы: образцы ткани для иммуногистохимического исследования взяли у 55 больных раком щитовидной железы (ЩЖ), 40 пациентов — с аденомой ЩЖ, 40 — с гиперпластическими процессами ЩЖ, контролем служили 20 образцов неизмененной ткани ЩЖ (аутопсия). Результаты: экспрессия синдекана-1 и Е-кадгерина в нормальных фолликулярных эпителиальных клетках ЩЖ выражена интенсивно, с преимущественной локализацией в базолатеральной мембране. Не отмечали существенных различий в экспрессии обеих молекул при гиперпластических процессах по сравнению с аденомами ЩЖ. Однако таковая значительно снижена в образцах высокодифференцированной карциномы по сравнению с нормальным эпителием ЩЖ (p = 0,0001 и p = 0,032 соответственно), а также при низкодифференцированном и анапластическом раке по сравнению с высокодифференцированными опухолями ЩЖ (p = 0,0037 для синдекана-1 и p = 0,075 для Е-кадгерина). Выводы: снижение экспрессии синдекана-1 и Е-кадгерина, сопровождающееся снижением способности клеток к дифференциации, может быть частью механизма прогрессирования заболеваний ЩЖ

Expression of vascular endothelial growth factor (VEGF) and association with microvessel density in small-cell and non-small-cell lung carcinomas

Recent studies have demonstrated that tumor angiogenesis is a prognostic factor for various malignant neoplasms. Specifically, in non-small-cell lung carcinomas (NSCLCs) most reports show an association between neovascularization and vascular endothelial growth factor (VEGF) expression as well as the presence of metastases and survival, although a few reports do not agree with these findings. Angiogenesis is not clearly characterized in small-cell lung carcinomas (SCLCs), since they are rarely treated by surgery, and thus the available tissue for biological characterization is sparse. The aim of the present study was to investigate angiogenesis and the expression of VEGF in lung tumors. We examined 88 non-small-cell and 39 smallcell lung carcinomas. Angiogenesis was estimated by determining microvessel counts, with the use of anti- CD31 and anti-factor VIII antibodies and expression of VEGF was also evaluated immunohistochemically. Our data showed that in NSCLCs angiogenesis was more prominent in poorly-differentiated neoplasms and correlated with VEGF expression, therefore it is at least in part mediated by the latter. Interestingly, in SCLCs a higher vascularization was noted. However, there was no strong association with VEGF expression. Thus, smallcell lung carcinoma may represent a suitable neoplasm for testing antiangiogenic drugs in combination with chemotherapy. Nevertheless, antiangiogenic therapy should not be targeted specifically to the VEGF pathway, since in SCLCs other mediators of angiogenesis may be important as well

Bcl-2 expression in colorectal tumours. Correlation with p53, mdm-2, Rb proteins and proliferation indices

Immunostaining for bcl-2 protein was performed in 27 colorectal adenomas and 108 colorectal adenocarcinomas. The aim of the study was to determine bcl-2 expression in correlation with p53, mdm-2 and Rb expression, with proliferation indices (Ki-67-LI, PCNALI) as well as with conventional clinicopathological variables. A higher proportion of adenomas (30.8%) than carcinomas (16.7%) expressed bcl-2 and conversely, a lower proportion of adenomas (7.4%) than carcinomas expressed p53 (57.1 %), the difference being statistically significant (p<0.0001). No correlation of bcl-2 expression with p53 expression (parallel or inverse) as well as with the other parameters studied was observed in any tumour. The bcl-2+/p53- subgroup of cancers showed a trend for correlation with negative lymph node status. Our data suggest, that bcl-2 expression may be involved in the early phase of colorectal carcinogenesis regardless of p53 status, while p53 function may be involved in a late stage of the adenoma-carcinoma sequence. P53 is apparently not involved in the regulation of apoptosis in the colorectal neoplasias or perhaps bcl-2 expression, as an early event in colorectal tumours, may occur before changes of p53 take place. Tumours with bcl-2+/p53- immunophenotype are frequently associated with negative lymph node status and seem to have a less aggressive behavior

Osteonecrosis of the tibial plateau: Magnetic resonance imaging appearances with quantitation of lesion size and evidence of a pathogenesis of meniscal injury

Purpose: To determine the magnetic resonance (MR) imaging appearances of osteonecrosis of the tibial plateau and perform quantitative analysis of the extent of the necrotic area. Materials and Methods: Twenty-eight patients (34 knees) with osteonecrosis were retrospectively evaluated using MR imaging and other modalities where available. A computerized image analysis program that allowed quantification of the lesion size was used to obtain measurements of the extent of involvement, which were then incorporated into each stage of the disease. Results: The MR imaging findings of osteonecrosis of the tibial plateau included subchondral regions of abnormal signal intensity (n = 28), a double-line sign (n = 11), and fractures (n = 9). Meniscal tears and cartilage abnormalities were disclosed in the affected knee compartment with an equal frequency (n = 17). The size of the necrotic lesion varied among different stages of the disease as follows: 6.8% to 15.7% (stage I); 6.5% to 59.3% (stage II); 23.5% to 61.3% (stage III); and 34.3% to 75% (stage IV). The extent of involvement was greater in stage II than that in stage I (P &lt; 0.001) and in stage IV than that in stage III (P &lt; 0.05), whereas the extent of involvement in stage III was not significantly greater than that in stage II (P &gt; 0.05). Conclusions: The MR imaging characteristics of osteonecrosis of the tibial plateau are variable. The association of osteonecrosis at this site with meniscal tears and cartilage abnormalities has important implications for pathogenesis of the disease as it relates to physical stress. Quantification of the lesion size provides precise information for optimal staging of the disease. Copyright © 2010 by Lippincott Williams &amp; Wilkins

p63 expression in benign and malignant breast lesions

The p63 gene encodes six protein isoforms. The transactivating isoforms have similar actions with p53, while the N-isoforms inhibit transcription activation by p53 and transactivating isoforms. p63 is expressed in stratified epithelia and in basal cells of the prostate and salivary glands. In mammary epithelium p63 has been shown to be expressed only in the myoepithelial layer. In the present study we investigated the immunohistochemical expression of p63, in benign and malignant breast lesions, and compared it with known myoepithelial cell markers. Our material consisted of 140 benign and 126 malignant breast lesions. We used the antibodies anti-p63, anti-a-smooth muscle actin, anti-S-100 protein and anti-cytokeratin 14. In all benign lesions, p63 immunoreactivity was noted in the myoepithelial cell layer surrounding the luminal epithelial cells. A less continuous peripheral rim of myoepithelial cells was also highlighted with p63- staining in all situ carcinomas. All invasive breast carcinomas were devoided of peripheral p63 staining. Interestingly, strong nuclear p63 immunoreactivity was noted in a small fraction (5-15%) of epithelial cells in all cases of papillomatosis, in 62.5% of in situ ductal papillary-type carcinomas and in 33.3% of invasive papillary carcinomas. Comparable staining was observed with S-100. The stromal cells were unreactive to p63. Our findings suggest that p63 is a sensitive and specific myoepithelial marker, and may be included in immunohistochemical panels aiming to identify myoepithelial cells in problematic breast lesions. Regarding papillary neoplasms, it is possible that tumor cells acquire and exhibit at least in part a myoepithelial differentiation program

lmmunohistochemical expression of Retinoblastoma gene product (Rb), p53 protein, MDM2, c-erbB-2, HLA-DR and proliferation indices in human urinary bladder carcinoma

Archival biopsy specimens from transitional cell bladder cancers (n=88) were analysed immunohistochemically for the expression of the retinoblastoma (Rb) gene protein, p53, mdm2, c-erbB-2, HLA-DR antigen and proliferation indices. An altered nuclear expression of Rb, p53 and mdm2 was observed in 55.2%, 33.3% and 18.2% of tumors respectively. Cytoplasmic membrane immunoreactivity (>25% tumor cells) for c-erbB-2 was detected in 14.1% of tumors and aberrant HLA-DR antigen cytoplasmic staining (>5% of tumor cells) in 22.2% of the cases. P53 overexpression was associated with higher tumor grade and stage. Aberrant HLA-DR antigen expression and PCNA were also correlated with the grade of differentiation and tumor stage. MIBl was statistically correlated with stage. pRb scores and HLADR antigen expression were correlated with proliferation activity as determined by PCNA and MIBl immunostaining. p53 protein was also strongly correlated with the proliferation index PCNA. A strong correlation between PCNA and MIBl (pc0.0001) was also found. In addition a statistically positive correlation between p53 and HLA-DR antigen expression was observed. Our data show that, although pRb and p53 protein expressions are not associated between them, they may contribute to the growth fraction of the bladder cancer. In addition, p53 and HLA-DR antigen expression could be indicators of aggressive behavior of bladder cancer

Glycoprotein CD44 expression in benign, premalignant and malignant epithelial lesions of the larynx. An immunohistochemical study including

CD44 is an integral membrane glycoprotein that has diverse functions in cell-cell and cell-substrate interactions. It has been suggested that it may be a determinant of metastatic and invasive behavior in carcinomas. The immunohistochemical expression of CD44 was examined in a series of 34 squamous cell carcinomas, 13 in situ carcinomas, 35 cases with various degrees of epithelial dysplasia, 10 papillomas and 17 cases of keratosis. We used the monoclonal mouse antihuman phagocytic glycoprotein-1 CD44 (clone DF 1485), on formalin-fixed, paraffin-embedded tissue. CD44 expression was correlated with the expression of Rb and p53 proteins, with the proliferative indices Ki-67 and PCNA as well as with conventional clinicopathological data. The mean value of CD44 expression was 78.84 in squamous cell carcinomas, 78.04 in in situ carcinomas, 54.93 in dysplasia, 26.8 in papillomas and 24.97 in keratosis. There was no significant difference of CD44 expression between in situ and invasive carcinomas. However, a strong difference of reaction between carcinomas and the other cases was observed. CD44 expression was statistically higher in dysplastic lesions than the cases of keratosis (p<0.0001) and papillomas (p=0.01). In the group of invasive carcinomas, CD44 expression was statistically correlated with pRb (p=0.011), while in preinvasive lesions it was correlated with PCNA (p=0.016). The relationship with the degree of dysplasia or grade of carcinoma and p53 protein expression was insignificant. These observations suggest that CD44 expression may be involved in the multiple mechanism of the development and progression of laryngeal lesions and may help to predict the risk of transformation of the benign or precancerous lesions to cancer

Expression of syndecan-1 in chronic liver diseases: Correlation with hepatic fibrosis

Background/Aim: The mechanisms underlying the contribution of the heparan sulfate proteoglycan syndecan-1 to liver tissue injury and to crucial biological processes, such as fibrogenesis, remain to be elucidated. Therefore, we investigated the immunohistochemical expression of syndecan-1 in chronic liver diseases (CLDs) and its probable role in hepatic fibrosis. Materials and Methods: Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections of biopsy material obtained from 128 patients diagnosed with CLDs. The correlation between syndecan-1 expression and the stage of fibrosis was investigated. Results: According to the severity of fibrosis, cases were categorized into three groups: early fibrosis; intermediate fibrosis; advanced fibrosis. Syndecan-1 expression was significantly enhanced in advanced fibrosis compared to early (p&lt;0.012) and intermediate (p&lt;0.003) fibrosis. Conclusion: In CLDs, syndecan-1 immunohisto-chemical overexpression was found to be positively correlated with the severity of fibrosis, suggesting its probable role in hepatic fibrogenesis. © 2021 International Institute of Anticancer Research. All rights reserved

Expression of matrix metalloproteinase-9 (gelatinase B) in benign, premalignant and malignant laryngeal lesions

The matrix metalloproteinases (MMPs) are a family of proteolytic zinc-containing enzymes, which are responsible for the breakdown of the extracellular matrix components in pathological and physiological conditions. They are involved in basement membrane disruption, stroma and blood vessel penetration, metastasis and more recently there is evidence that they participate in tumor growth and angiogenic events. Matrix metalloproteinase 2 and 9 (MMP 2 and 9) belong to the gelatinases, a subgroup of MMPs, and have the capacity to degrade the triple helix type IV collagen of basal lamina of the basement membrane. With the present study, we tried to demonstrate the expression of MMP-9 immunohistochemically, comparatively in benign, premalignant and malignant lesions of the larynx. We studied 154 laryngeal lesions including 55 squamous cell carcinomas, 8 in situ carcinomas, 54 cases of dysplasia (of low and intermediate grade), 13 papillomas and 24 cases of keratosis. Overexpression of MMP 9 was observed in 74.4% and 50% in invasive and in situ squamous cell carcinomas respectively. In dysplastic cases, in papillomas and in keratoses the percentage of overexpression was 62.9%, 61.53% and 54.16% respectively and the expression of MMP-9 was significantly higher in invasive squamous cell carcinomas compared to dysplasias (p=0.000004). Also significantly higher was the expression of MMP-9 in dysplastic cases compared to papillomas (p=0.023). The MMP-9 expression was related neither to survival nor to the other available clinicopathological parameters (tumor size, grade, clinical stage, lymph node status and patient age). In conclusion, our study indicates that the expression of MMP-9 is up-regulated in a stepwise fashion, with two main steps, the first one, when a dysplastic lesion evolves and the next one, when the dysplasia progresses to invasive carcinoma

Immunohistochemical expression of superoxide dismutase (MnSOD) anti-oxidant enzyme in invasive breast carcinoma

The most important cellular protective mechanisms against oxidative stress are antioxidant enzymes. Their action is based on decomposal of reactive oxygen species (ROS) and their transformation to H2O2. Within the mitochondria manganese superoxide dismutase (MnSOD) affords the major defense against ROS. In this study we investigated tissue sections from 101 breast carcinomas for the immunohistochemical expression of MnSOD protein and these results were assessed in relation to various clinicopathological parameters, in order to clarify the prognostic value of this enzyme. The possible relationship to hormone receptor content, anti-apoptotic protein bcl-2, p53 and cell proliferation was also estimated. High expression levels were observed, as 79/101 (78,2%) cases expressed strong immunoreactivity. In this study MnSOD increased in a direct relationship with tumor grade and is therefore inversely correlated with differentiation (p=0.0004). Furthermore, there was a strong positive correlation between MnSOD expression and p53 protein immunoreactivity (p=0.0029). The prognostic impact of MnSOD expression in determining the risk of recurrence and overall survival with both univariate (long-rang test) and multivariate (Cox regression) methods of analysis was statistically not significant. These results indicate that neoplastic cells in breast carcinomas retain their capability to produce MnSOD and thus protected from the possible cellular damage provoked by reactive oxygen species. In addition, MnSOD content varies according to the degree of differentiation of breast carcinoma