Agata Lazar

RCAS1 decidual immunoreactivity during placental abruption: immune cell presence and activity.

RCAS1 is a protein responsible for the suppression of cytotoxic immune response during gestation. The present study evaluates the immunoreactivity level of RCAS1 with respect to immune cell status during placental abruption (PA) and retained placental tissue (RPT).

The association between RCAS1 expression in laryngeal and pharyngeal cancer and its healthy stroma with cancer relapse

BackgroundThe purpose of this study has been to establish the level of RCAS1 – a membrane protein expressed in various cancer cells and able to induce apoptosis of CTLs and NK cells in pharyngeal and laryngeal cancer and its clear surgical margin – with respect to clinicopathological features and to patients follow up and evaluate its possible role in cancer relapse.MethodsA total of 122 tissue samples were obtained: 51 samples from laryngeal and pharyngeal squamous cell carcinoma, 51 samples from the clear surgical margins of these tumors, and 20 tissue samples derived from the healthy mucous membranes of the upper respiratory tract mucosa of patients without cancerous tumors. Patients were observed for a total of 4 years following surgical treatment. The level of RCAS1 expression was assessed by immunohistochemistry and Western blot.ResultsRCAS1 was identified in all laryngeal and pharyngeal carcinomas and in almost all the clear surgical margin samples. The level of RCAS1 expression was significantly higher in the cancerous samples than in the clear surgical margins and was determined to be related to the grade of the cancer and the presence of lymph node metastases. In cases of cancer relapse, significantly higher levels of RCAS1 expression were observed in the clear surgical margins.ConclusionSelective cytotoxic immune cell suppression concomitant with tumor growth and associated with RCAS1 expression seems to be an important event connected with cancer relapse.

Comparison of RCAS1 and metallothionein expression and the presence and activity of immune cells in human ovarian and abdominal wall endometriomas

BackgroundThe coexistence of endometrial and immune cells during decidualization is preserved by the ability of endometrial cells to regulate the cytotoxic immune activity and their capability to be resistant to immune-mediated apoptosis. These phenomena enable the survival of endometrial ectopic cells. RCAS1 is responsible for regulation of cytotoxic activity. Metallothionein expression seems to protect endometrial cells against apoptosis. The aim of the present study was to evaluate RCAS1 and metallothionein expression in human ovarian and scar endometriomas in relation to the presence of immune cells and their activity.MethodsMetallothionein, RCAS1, CD25, CD69, CD56, CD16, CD68 antigen expression was assessed by immunohistochemistry in ovarian and scar endometriomas tissue samples which were obtained from 33 patients. The secretory endometrium was used as a control group (15 patients).ResultsThe lowest metallothionein expression was revealed in ovarian endometriomas in comparison to scar endometriomas and to the control group. RCAS1 expression was at the highest level in the secretory endometrium and it was at comparable levels in ovarian and scar endometriomas. Similarly, the number of CD56-positive cells was lower in scar and ovarian endometriomas than in the secretory endometrium. The highest number of macrophages was found in ovarian endometriomas. RCAS1-positive macrophages were observed only in ovarian endometriomas. CD25 and CD69 antigen expression was higher in scar and ovarian endometriomas than in the control group.ConclusionThe expression of RCAS1 and metallothionein by endometrial cells may favor the persistence of these cells in ectopic localization both in scar following cesarean section and in ovarian endometriosis.

Analysis of metallothionein and vimentin immunoreactivity in pharyngeal squamous cell carcinoma and its microenvironment

Metallothionein (MT) has been shown to have pro-proliferative anti-apoptotic activity and to be involved in microenvironment remodeling. The aim of this study has been to determine whether the changes in MT and vimentin immunoreactivity observed in cancer and its microenvironment are related to the local spread of the disease. The immunoreactivity levels of both MT and vimentin were evaluated together with CD56 and CD57 antigens in 49 tissue samples taken from patients with squamous cell carcinoma originating from the palatine tonsils and in 20 tissue samples derived from patients with chronic tonsillitis (the reference group). MT immunoreactivity levels were statistically significantly higher in the tissue samples from squamous cell carcinoma than in those of the reference group and also higher in the squamous cell carcinoma samples compared with the stromal samples. Moreover, stromal fibroblasts exhibited high vimentin and MT immunoreactivity levels. Statistically significantly higher MT immunoreactivity levels within the tumor cells were identified in patients with the presence of lymph node metastases in contrast to those patients without such metastases. Vimentin was detected in both the tumor and the stromal tissue samples and presented an interesting pattern of staining strongly expressed within the stroma and the septal architecture of the tumor. The number of CD56- and CD57-positive lymphocytes identified in tissue samples both from squamous cell carcinoma and from the stroma was statistically significantly lower than that in the reference group. MT expression by tumor cells is thus associated with an aggressive phenotype of the tumor and the ability to create metastases.

The Potential Role of MT and Vimentin Immunoreactivity in the Remodeling of the Microenvironment of Parotid Adenocarcinoma

A tumor stimulates the remodeling of its microenvironment in order to control and accelerate its own growth and to initiate metastases. To create metastases the tumor cells must first acquire the ability to detach from the main tumor and to adhere to, invade, and degrade the adjacent extracellular matrix. The cells must then be able to enter the lumen of the vessels where they home the distant tissues and organs by forming secondary tumors. The acquisition of this phenotype is related to the phenomenon of epithelial-to-mesenchymal transition. On the molecular level, this process is typified by a change in the expression of epithelial markers and by the enhancement of the expression of mesenchymal markers like vimentin that are responsible for cell migration and invasion. Metallothioneins have been shown to help protect against apoptosis. The expression of MT by tumor cells plays an important and complex role not only because of its pro-proliferative, anti-apoptotic activity, but also because it inhibits the immune response. The aim of the present study was to evaluate the immunoreactivity of vimentin and MT in the salivary gland adenocarcinoma and its stroma in order to observe the phenomenon of stromal remodeling. The tissue samples of salivary gland adenocarcinomas and their stromas and the palatine tonsils which constituted the reference group were obtained during routine surgical procedures. The immunoreactivity of vimentin, metalothionein, CD56, CD57 antigens was evaluated by the immunohistochemistry method in 30 tissue samples of parotid adenocarcinoma. The patient’s consent was obtained in each case. A statistically significantly higher level of MT immunoreactivity was observed in the adenocarcinoma tissue slides than in either the stromal slides or the reference slides while no differences in MT immunoreactivity were detected when the stroma and reference tissue slides were compared. A statistically significantly higher vimentin immunoreactivity level was identified in the tumor microenvironment tissue slides than in the tumor tissue slides, and a statistically significantly higher level of vimentin immunoreactivity was identified in the tumor microenvironment slides than in the slides of the reference tissue, while no differences were identified between the adenocarcinoma tissue slides and the reference slides with respect to vimentin immunoreactivity. A statistically significantly higher number of CD56- and CD57-expressing cells were identified in the reference tissue slides than in either the adenocarcinoma or stromal slides. In conclusion, the stroma of salivary gland adenocarcinoma in this study has been characterized by remodeling. The remodeling is represented by the expression of both vimentin and MT and by a deficit of CD57- and CD58-expressing cell infiltration. This situation would seem to be the result of immune tolerance for the tumor developing within the tumor microenvironment. Furthermore, the presence of MT and vimentin immunoreactivity in the fibroblasts of the tumor stroma may constitute a marker of active tissue remodeling.

Analysis of Metallothionein, RCAS1 Immunoreactivity Regarding Immune Cell Concentration in the Endometrium and Tubal Mucosa in Ectopic Pregnancy during the Course of Tubal Rupture

Introduction: Tubal rupture seems to be linked to a disturbance in maternal immune response and trophoblast cell invasion. The immunomodulating activity of endometrial cells is necessary for the coexistence of activated immune cells and endometrial cells. RCAS1 and metallothionein (MT) participate in this process. Material and Methods: Tissue samples derived from fallopian tubes and endometrium were collected during one surgical procedure and divided into three groups: unruptured ectopic pregnancy (EP) without bleeding, unruptured EP with hemorrhage into the peritoneal cavity, and ruptured tubal pregnancy. Immunoreactivity of MT, RCAS1, CD56, CD3, CD69 and CD25 were assessed by immunohistochemical methods. Results: The number of CD3+ and CD56+ cells as well as CD69 antigen immunoreactivity in ruptured tubal mucosa of EP were statistically significantly higher than those measured for unruptured EP without bleeding, while at the same time the number of CD56+ cells in endometrium was statistically significantly lower. The growth of immune cell numbers in tubal mucosa during tubal rupture was not associated with an adequate MT and RCAS1 level. Conclusion: Tubal perforation seems to be linked to a concentration of immune cells and a growth of their activity without an adequate increase of the level of proteins compensating for immune cell response.

Ectopic thymic tissue in the mediastinum: limitations for the operative treatment of myasthenia gravis

OBJECTIVES The aim of the study was to investigate the distribution of ectopic thymic tissue in the mediastinum and to evaluate the possible relevance of this distribution to the therapeutic yield of thymectomies in patients with myasthenia gravis. METHODS In this prospective autopsy study, mediastinal dissections were performed on 50 cadavers without any previously known intrathoracic pathology. The initial dissection was performed in the same way as during the maximal thymectomy. The second stage consisted of dissecting areas of fatty tissue located out of reach of the standard maximal thymectomy, such as the perithyroid, periaortic, peritracheal and retrotracheal areas, as well as the areas adjacent to the right and left phrenic and recurrent laryngeal nerves. Each specimen was independently examined by two pathologists for ectopic thymic tissue. RESULTS There were 41 (82%) male and 9 (18%) female cadavers, with a mean age of 44.3 years (range: 15-75). Ectopic thymic tissue was detected in 32 out of 50 cadavers (64%). In 10 (20%) cadavers thymic foci were found in locations accessible to the standard surgical intervention and in 22 (44%)-in inaccessible locations. Thymic tissue incidence in individual locations was as follows: retrothyroid, 3 (6%); peritracheal, 5 (10%); retrotracheal, 1 (2%); right phrenic nerve, 2 (4%); left phrenic nerve, 14 (28%); right recurrent laryngeal nerve, 2 (4%); left recurrent laryngeal nerve, 2 (4%) and periaortic, 0. CONCLUSIONS The incidence of ectopic thymic tissue in the mediastinum is common. Although some improvements in the results of thymectomies may be expected with more extensive dissection, the frequent presence of thymic foci in anatomical locations hardly accessible to surgical intervention may be the true limitation for surgical treatment of myasthenia.

The evaluation of metallothionein expression in nasal polyps with respect to immune cell presence and activity

BackgroundThe expression of metallothionein (MT) is involved in acquiring resistance to immune-mediated apoptosis; it is also a negative regulator of the immune response. Nasal polyps are typified by a resistance to immune-mediated apoptosis as well as by excessive immune cell infiltration. RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a membrane protein capable of inducing the apoptosis of CTLs and NK cells. The aim of the present study has been to explore the expression of metallothionein with respect to immune cell presence and immune cell activity. In our study, we identified immune cells using CD4 and CD68 antigen expression and evaluated their activity using CD25 antigen expression. We then analyzed metallothionein, RCAS1, CD25, CD4, and CD68 in a sampling of 50 nasal polyps using the immunohistochemistry method. We were able to divide the nasal polyps into three main groups according to their predominant immune cell infiltration: eosinophilic nasal polyps (21 cases), lymphocytic nasal polyps (17 cases), and neutrophilic nasal polyps (12 cases).ResultsIn the present study, statistically significant differences between the MT expression in the epithelium and that in the stroma of the nasal polyps along with the accompanying alterations in activation markers on immune cells were found and the number of macrophages in both the eosinophilic and the lymphocytic nasal polyps was assessed. RCAS1-expressing macrophages were found only in the eosinophilic nasal polyps.ConclusionMT expression seems to favor the survival of nasal polyp epithelial cells in the adjacent area of increasingly cytotoxic immune activity. RCAS1-expressing macrophages seem to participate in creating the immune suppressive microenvironment and so help to sustain local inflammation.

RCAS1 Decidual Immunoreactivity in Severe Pre-Eclampsia: Immune Cell Presence and Activity

Pre‐eclampsia seems to be related to the disturbance of immune tolerance regulation during pregnancy. Receptor‐binding cancer antigen expressed on SiSo cells (RCAS1) decidual level alterations were concomitant with changes in immune cell number and activity in decidua. As decidual immunomodulating activity participates in the development of immune tolerance during pregnancy, we aimed to evaluate the immunoreactivity level of decidual RCAS1 with respect to the presence and activity of immune cells.

The Involvement of RCAS1 in Creating a Suppressive Tumor Microenvironment in Patients with Salivary Gland Adenocarcinoma

The tumor microenvironment is the tissue that determines the growth and progression of the tumor as well as its ability to initiate metastases. The aim of the present study has been to evaluate the role of RCAS1 in creating the suppressive tumor microenvironment in cases of parotid adenocarcinoma. The tissue samples of salivary gland adenocarcinomas and their stroma and the palatine tonsils which constituted the reference tissue sample group were obtained during routine surgical procedures. The immunoreactivity of RCAS1, CD3, CD25, CD68, CD69, and Foxp3 antigens was then evaluated by using the immunohistochemistry method. The patient’s consent was obtained in each case. A statistically significantly higher RCAS1 immunoreactivity level was found in the adenocarcinoma tissue samples in comparison to that found in the stromal tissue samples. A statistically significantly higher RCAS1 immunoreactivity was also identified in the adenocarcinoma tissue samples derived from patients who had lymph node metastases in comparison to patients without such metastases. Additionally, we observed the presence of RCAS1-positive macrophages in the stromal tissue samples. The infiltration of CD68-positive cells was significantly stronger in the adenocarcinoma and stromal tissue slides than in the reference group tissue slides; moreover, the infiltration was a good deal more prominent in the stromal tissue than in the adenocarcinoma tissue. The CD68 immunoreactivity levels in both the tumor and stromal tissue samples were found to be significantly higher in those patients who had lymph node metastases than in the patients without such metastases. Additionally, the infiltration of CD3- and CD25-positive cells was more prominent in the reference tissue slides than in the adenocarcinoma and stromal tissue slides, and was stronger in the adenocarcinoma tissue than in the stromal tissue. Furthermore, the infiltration of Foxp3-positive cells was seen exclusively in the stroma whereas it was not even detected in the adenocarcinoma tissue. Lastly, the Foxp3-positive cell infiltration was more prominent in the stromal tissue than in the reference group tissue. The present study demonstrates that RCAS1 expression by both tumor cells and tumor-associated macrophages may participate in creating the immunosuppressive microenvironment in parotid gland adenocarcinoma, thus promoting tumor development as well as metastases.