RCAS1 Expression Research Articles

Clinical significance of RCAS1 as a biomarker of ovarian cancer

Expression of RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is associated with advanced disease of various malignancies including ovarian cancer. Proteolytic cleavage of RCAS1 at extracellular domains (ectodomain shedding) yields soluble RCAS1. Although RCAS1 can induce apoptosis in normal peripheral lymphocytes, its clinical significance and biologic function in ovarian cancer patients are unclear. Here, we evaluated serum RCAS1 concentrations to clarify its clinical significance and biologic activity in ovarian cancer. Via ELISA, we measured serum RCAS1 concentrations in samples from 75 healthy blood donors and 97 patients, 36 with ovarian benign tumor and 61 with ovarian cancer. We correlated via statistical means the RCAS1 values with patients' clinicopathologic variables. We assessed inhibition of growth of K562 cells, which express the putative RCAS1 receptor, via WST-1 assay of serum samples to clarify RCAS1's biologic activity. Ovarian cancer patients had significantly higher serum RCAS1 concentrations than did healthy blood donors and ovarian tumor patients (P<0.05). RCAS1 level was significantly different according to histologic subtype for both ovarian tumor and cancer patients (P=0.0266 and 0.0074, respectively). RCAS1 values were also significantly associated with response to treatment (P<0.001). The WST-1 assay showed that patients' serum induced K562 cell growth inhibition, but this effect partially recovered after immunodepletion of RCAS1 (P=0.0074). RCAS1 may be a biomarker of ovarian cancer by virtue of its ability to predict results of treatment and inhibit immune cell growth.

Prognostic Significance of RCAS1 Expression in Relation to the Infiltration of Dendritic Cells and Lymphocytes in Patients with Esophageal Carcinoma

RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) expression was determined in 107 esophageal carcinoma patients by immunohistochemical procedures and compared with tumor infiltrating lymphocyte (TIL) and dendritic cell (DC) infiltration to evaluate the effect of RCAS1 on immune responses in esophageal carcinoma. RCAS1 immunoreactivity was detected in 59 of 107 patients (55.1%). RCAS1 expression was significantly correlated with the depth of invasion, lymph node metastasis, and histologic stage. RCAS1 expression tended to be correlated with a lower TIL density in tumors with marked DC infiltration. The survival time for patients with RCAS1-negative tumors was significantly longer than that for patients with RCAS1-positive tumors. Especially, the prognosis was predicted by RCAS1 in cases with marked DC infiltration. Multivariate analysis revealed that RCAS1 expression was an independent prognostic factor. RCAS1 expression may play an important role in evading the immunological defense mechanisms in esophageal carcinoma.

Cycle dependent expression of endometrial RCAS1 and the activity of immune cells

Cycle dependent expression of endometrial RCAS1 and the activity of immune cells

RCAS1 induced by HIV-Tat is involved in the apoptosis of HIV-1 infected and uninfected CD4 + T cells

HIV-1 infection is known to lead to a massive depletion of CD4 + T cells, and the Fas/FasL and TRAIL/TRAIL-receptor systems have been reported to be one of the mechanisms of CD4 + T cell apoptosis in HIV-1 infection. RCAS1 (a receptor-binding cancer antigen expressed on SiSo cells) is also an apoptosis-associated protein that induces apoptosis in receptor positive-cells including T cells, and NK cells. To investigate the role of RCAS1 in HIV-1 infection, we stimulated CD4 + T cells, monocytes, and several cell lines by HIV-Tat protein and thus showed that Tat significantly increased the mRNA transcription levels and the secretion of soluble RCAS1 in CD4 + T cells and monocytes. We also showed that the apoptosis induced by HIV-Tat was blocked by inhibiting the expression of RCAS1, using small interfering RNA (siRNA), which was specific for RCAS1. These results indicate that RCAS1 is one of the mechanisms of CD4 + T cell depletion induced by HIV infection.

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.

Clinical significance of RCAS1 as a biomarker of uterine cancer

Objectives. Expression of RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is associated with prognosis of various malignancies including uterine cancer. Proteolytic cleavage of RCAS1 at extracellular domains (ectodomain shedding) yields soluble RCAS1. Although RCAS1 can induce apoptosis in normal peripheral lymphocytes, its biologic function in cancer patients is unclear. Here, we evaluated serum RCAS1 concentrations to clarify its biologic activity in uterine cancer. Methods. Via ELISA, we measured serum RCAS1 concentrations in samples from 54 healthy blood donors and 113 patients—63 with cervical cancer and 50 with endometrial cancer. We also counted the peripheral lymphocyte number. We correlated via statistical means the RCAS1 values with patients' clinicopathologic variables. We assessed inhibition of growth of K562 cells, which express the putative RCAS1 receptor, via WST-1 assay of serum samples to clarify RCAS1's biologic activity. Results. Uterine cancer patients had significantly higher serum RCAS1 concentrations than did healthy blood donors ( P < 0.05). Patients with adenocarcinoma had significantly higher RCAS1 concentrations than did those with squamous cell carcinoma ( P = 0.0340). RCAS1 values were also significantly associated with response to treatment ( P < 0.001). FasL and TNF-α serum concentrations were not significantly different for the different groups, however. The WST-1 assay showed that patients' serum induced K562 cell growth inhibition, but this effect partially recovered after immunodepletion of RCAS1. Peripheral lymphocyte number and serum RCAS1 concentration were inversely related ( P = 0.0310). Conclusion. RCAS1 may be a biomarker of uterine cancer because of its potential to predict results of uterine cancer treatment and inhibit growth of immune cells.

Expression of tumor‐associated antigen RCAS1 and its possible involvement in immune evasion in oral squamous cell carcinoma

RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is known to induce apoptosis in its receptor-positive cells. The authors investigated RCAS1 expression in oral squamous cell carcinoma (SCC) and its association with the apoptosis of tumor-infiltrating lymphocytes (TILs). In 130 patients with oral SCC, the expression of RCAS1 in tumor cells was immunohistochemically examined and the apoptosis of TILs was examined by Terminal Deoxynucleotidyltransferase-mediated dUTP Nick End Labeling (TUNEL) staining. RCAS1 was detected both on the cytoplasm and the membrane of tumor cells in 41 of 130 cases (31.5%). Focusing on the expression at the invasive front interacting with host immune cells, RCAS1 was detected in 22 of 130 cases (16.9%). The percentage of TUNEL-positive TILs in cases with RCAS1-positive SCCs was significantly higher than in cases with RCAS1-negative SCCs (P < 0.0001). RCAS1 can be expressed on oral SCC cells and may be involved in the tumor escape from the host immune system by inducing the apoptosis of TILs.

Clinico-pathological significance of RCAS1 expression in gliomas: A potential mechanism of tumor immune escape

RCAS1, one of the tumor cell surface antigens, is strongly expressed in aggressive tumors. RCAS1 suppresses the in vitro growth of immune effector cells. We investigated the expression of RCAS1 in 57 gliomas using immunohistochemistry. Furthermore, we examined the association of the RCAS1 expression with the infiltration of tumor infiltrating lymphocyte (TIL). RCAS1 overexpression was significantly correlated with high histological grade and poor prognosis. Reduced infiltration and increased apoptosis of TILs was observed in RCAS1-positive regions. Apoptotsis of TILs appeared to be induced by RCAS1. RCAS1 expression in gliomas may play roles in tumor progression and tumor immune escape.

The analysis of RCAS1 and DFF-45 expression in nasal polyps with respect to immune cells infiltration

BackgroundNasal polyp constitutes a benign growth process in the nasal and sinus mucosa. RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a protein expressed mainly by various human cancer cells. It is not only the marker of cancer process and its expression can also be observed in physiological processes. It is responsible for the regulation of immune cells activity. DFF45 (DNA fragmenting factor) has been described as a substrate for caspase-3. DFF45 seems to play an important role in the onset of apoptotic process by acting probably through the regulation of DNA fragmentation. The aim of the study was to evaluate the ability of nasal polyps to regulate the cytotoxic immune response and to determine their resistance to apoptosis.ResultsThe higher RCAS1 level was identified in lymphocytic nasal polyps, the medium one in eosinophilic while the lowest was identified in neutrophilic. DFF-45 expression was higher in eosinophilic than in neutrophilic and lymphocytic nasal polyps.ConclusionThe changes in DFF-45 level in nasal polyps might indicate a different resistance to apoptosis mediated by immune cells. The alterations in RCAS1 expression indicate that nasal polyps have the ability to regulate the cytotoxic immune response.The breaking of resistance to immune mediated apoptosis in nasal polyps might have a new therapeutic impact.

A clinical and immunohistochemical study on gastrointestinal mesenchymal tumor (GIMT): RCAS1 as a predictor for recurrence of GIMT

Gastrointestinal mesenchymal tumors (GIMTs) are the most common mesenchymal tumors of the gastrointestinal tract. RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a cancer cell-surface antigen and has been identified as a prognostic factor in several cancer types. It is thought that tumor cells escape immune attack by expressing RCAS1, which induces apoptosis in receptor-positive immune cells. The current study was designed to elucidate the histogenesis of these tumors by using various immunohistochemical markers, and identify parameters that will help to establish the criteria of malignancy in the GIMT. We also discuss the clinicopathological significance of RCAS1 expression in the diagnosis and prognosis of GIMTs. A total of 70 cases of GIMTs were reviewed. Immunohistochemistry was performed between 1990 and 2000, with the avidin-biotin-peroxidase complex method on 3 microm-thick sections of formalin-fixed paraffin-embedded specimens of GIMTs. Antibodies to the following antigens were used: KIT (CD117), CD34 alpha-SMA, Desmin, cytokeratin, S-100 protein, p53, and RCAS1. Recurrence-free survival analysis was done with Stat View-J 5.0 statistical packages. Univariate analysis for a recurrence-free prognosis demonstrated that antibody detection of p53 expression (p=0.0333) and expression of RCAS1 (p=0.0008) is correlated with a significantly higher potential of recurrence. On multivariate analysis, tumor size and RCAS1 expression were independently and inversely correlated with recurrence-free survival. The expression of RCAS1 has not previously been reported in GIMT; indeed, our study suggests that the expression of RCAS1 is correlated with recurrence not only in carcinomas, but also in mesenchymal tumors.

Expression of RCAS1 in Female Genital Organs

Receptor-binding antigen expressed on a human uterine adenocarcinoma cell line, SiSo (RCAS1), has been reported to be a prognostic factor of various malignant tumors, and it has also been proven to induce apoptosis of lymphoid cells. However, its normal distribution and function have not yet been elucidated. The purpose of this study was to disclose the distribution of RCAS1 expression in normal female genital organs. Immunohistochemical staining using anti-RCAS1 and anti-MIB-1 antibodies was performed on 123 surgical specimens of a histologically normal uterus, ovary, or fallopian tube from 66 patients, and the apoptotic index was determined. In uterine cervical glands, the expression of RCAS1 was seen in 93% of the cases, and it was mainly localized in the superficial cervical glands. Near the areas of squamous metaplasia, RCAS1 was strongly expressed in all samples. In the uterine cervical squamous epithelium, RCAS1 was seen in 84% of cases. In the uterine corpus, RCAS1 was seen in 87% of all cases, and it was mainly expressed in the endometrial glands of basalis layer. There was significant positive correlation between age and RCAS1 expression, but no significant difference was found regarding the endometrial status and RCAS1 expression in endometrium. No significant correlation was found between RCAS1 expression and MIB-1 index/apoptotic index. RCAS1 may affect these metaplastic processes and tumor progression.

Metallothionein and RCAS1 expression in comparison to immunological cells activity in endometriosis, endometrial adenocarcinoma and endometrium according to menstrual cycle changes

Objective. Endometrium is a specialized organ in which phenomena controlling the level of cell proliferation and apoptosis are marked. The aim of our study was to determine the presence of proteins involved in apoptosis and proliferation: RCAS1, MT and the number of CD56-positive cells and their activity to elucidate their possible role in the development of adenocarcinoma and endometriosis. Materials and methods. MT, RCAS1, CD56-positivity and CD69 expression were assessed in 55 tissue samples by Western blot and immunohistochemistry methods. Results. We found that endometrium during secretory menstrual cycle phase is characterized by significantly higher RCAS1 and higher MT expression than in proliferative phase. The number of CD56-positive cells and the CD69 antigen expression was significantly increased. Endometrial adenocarcinoma was characterized by significantly increased RCAS1 expression, while MT expression was comparable to the level found in the secretory phase. The number of CD56-positive cells was significantly decreased and their activity was comparable to the level found in the secretory phase. Endometriosis was accompanied by significantly lower RCAS1 and MT expressions, with lower number of CD-56 positive cells and lower expression of CD69 antigen in comparison to the secretory phase. Conclusions. The ability of endometrium to determine cytotoxic activity (RCAS1 expression changes) and high protection against DNA damage (MT expression) with concomitant changes in the number of immune cells and their activity, observed in normal endometrium during the menstrual cycle phases seems to be fundamental for pathological features of endometrial adenocarcinoma and endometriosis.

Invasive potency related to RCAS1 expression in uterine cervical cancer

Objectives. RCAS1 expression is significantly associated with clinical prognosis in various human cancers, which suggests that RCAS1 may be involved in acquisition of malignant phenotypes. To investigate the relationship between RCAS1 and one such characteristic, tumor invasiveness, we examined RCAS1 expression in cervical neoplasms ranging from the precancerous state to invasive cancer. Methods. RCAS1 expression was studied retrospectively via immunohistochemical methods. Samples consisted of biopsy tissue from 90 patients with intraepithelial neoplasia and resected tumor tissue from 154 patients with invasive cancer. Statistical analysis was done to correlate RCAS1 expression and clinicopathologic variables in patients with a depth of cancer cell invasion into stromal tissue of >5 mm. Results. RCAS1 expression was detected in patients with intraepithelial cancer and invasive cancer but not in patients with dysplasia. The occurrence and degree of RCAS1 expression increased with the depth of invasion. In patients with invasive cancer, RCAS1 overexpression was significantly correlated with invasion of the lymph-vascular space, lymph node metastasis in two or more sites, and tumor volume; RCAS1 expression was not associated with histologic subtype. Overall survival rates for patients with RCAS1 overexpression were significantly shorter than those for patients without RCAS1 overexpression. In connective tissue surrounding tumor cells, the number of cells expressing vimentin significantly decreased in relation to RCAS1 expression level. Moreover, significant associations between expression levels of RCAS1 and those of MMP-1 and laminin-5 were found. Conclusion. RCAS1 may contribute to acquisition of malignant uterine cervical phenotypic characteristics including invasion, metastasis, and tumor growth via connective tissue remodeling.

Current concepts of tumor-infiltrating lymphocytes in human malignancies

Tumor-infiltrating lymphocytes (TILs) develop as manifestations of the recognition and defense against malignant cells by the host immune system. TILs were literally defined as “tumor-infiltrating lymphocytes”, which a posteriori locate within the tumor tissues. Although such cells can be found, they fail to control the growth of tumor. Many have proposed diverse mechanisms for dysfunction of TILs with regard to the roles of immunosurveillance against cancer. However, only a few cancer types, e.g. melanoma, have seen the benefits brought by activating these cells for immunotherapy. Functional defects of TILs have been linked to abnormalities of signaling molecules; however, there is conflicting data. The death of TILs was attributed to expression of cancer-derived FasL, PD-1 and RCAS1, and cancer-induced activation-induced cell death (AICD). Confirmed by studies using TILs and animal models, the compromise of tumor-specific immune responses was thought to result from not only mechanisms of clonal anergy but also exhaustion and/or deletion. Furthermore, functional cytotoxic CD8 + TILs might be rendered incompetent by cancer-induced up-regulation of inhibitory NK receptors or proximal signaling abnormalities. Additionally, immune privilege was partly attributed to recruitment of regulatory T cells to the tumor sites. The failure of IL-2 signaling, which stands at the center of T cell functionalities, had been linked to the enzymatic activity of cancer-derived matrix metalloproteinases (MMPs). Finally, the exploitation of IDO expression, an important enzyme in pregnancy-related immunosuppression, by cancer cells might play a role in tumor immunity. The disparity of cancer types, origin, developmental stages and individual genetic backgrounds likely account for differences, or even contradictions, which might be the reason why immunotherapy works only on a few cancer types. Delineating the mechanisms behind functional defects of TILs can help not only boost chances of the development of a successful cure but understand the not fully identified roles played by immune system in the face of malignancies.

The molecular changes during placental detachment

Objectives RCAS1 is a membrane protein that plays a role in the maintenance of maternal immune tolerance during pregnancy. The work presented here demonstrates the results of RCAS1 expression in placenta in cases of placental abruption and patients with retained placental tissue during the third stage of labor. Study design The placenta tissue samples were obtained during vaginal and cesarean delivery (derived from 117 pregnancies). Pregnant women were divided into four groups according to the onset of labor and the time of placental detachment in term labors. The samples were analyzed by the Western blot method. Statistical analysis was performed using the Shapiro–Wilk procedure. The Mann–Whitney test and Student's t-test were applied to compare the differences between parametric data. Results The average relative amount of RCAS1 observed in those patients with retained placental tissue was statistically significantly higher than in the patients with placental abruption. Conclusion The differences observed in placental RCAS1 levels confirm the participation of this protein in the inhibition of maternal immune response during gestation. The present results also indicate that RCAS1 participates in the changes in the maternal immune system that take place during parturition and reinforce its potential involvement in the mechanism of placental abruption.

Clinical significance of the expression of tumor-associated antigen, RCAS1, and its soluble protein in pleural fluid in malignant mesothelioma

RCAS1 is a type II membrane protein which is also secreted as a soluble protein. RCAS1 may play a role in evading immune surveillance by tumor cells and be responsible for the aggressive behavior of tumors. We examined the usefulness of RCAS1 in the follow-up of malignant mesothelioma. In addition, we examined the usefulness of its soluble protein (sRCAS1) in pleural effusion for the diagnosis of malignant mesothelioma. We studied 38 patients with pleural malignant mesothelioma and examined the correlation between RCAS1 expression, clinicopathologic variables and overall survival. We also determined the pleural fluid sRCAS1 concentration with an enzyme-linked immunosorbent assay (ELISA). We found that 34 out of 38 (89.5%) malignant mesothelioma cells stained for RCAS1. The positive rate was 90.9% in biphasic type, 78.6% in epithelioid type, and 100% in sarcomatoid type. No statistically significant correlation was observed between RCAS1 expression and gender, age, histology or clinical stage. Interestingly, survival of the malignant mesothelioma patients with RCAS1 expression was significantly increased compared with those without (median survival time: 13.0 vs. 4.3 months, p=0.011). Multivariate analysis of prognostic factors, using the Cox proportional hazards model, revealed that RCAS1 expression had a significantly positive effect on survival. sRCAS1 concentrations in pleural fluid in malignant mesothelioma were lower than those in lung cancer (2.18+/-2.20 vs. 46.3+/-129 U/ml; p=0.019). RCAS1 expression is informative for the follow-up of malignant mesothelioma patients. In addition, sRCAS1 in pleural fluid may be useful for the diagnosis of malignant mesothelioma.

Resection of lung metastasis from gallbladder carcinoma: immunohistochemistry of RCAS1 and CD8 +T cells in primary and metastatic tumors

Advanced Gallbladder cancer has an extremely poor prognosis. We examined a patient with resectable gallbladder cancer with associated lung metastasis. A 64-year-old female patient, diagnosed with gallbladder cancer and a solitary benign lung tumor by imaging, was subjected to extensive cholecystectomy and extrahepatic bile duct resection. After one year, a follow-up CT indicated enlargement of the lung tumor; video-assisted right middle lobectomy was then performed. The lung tumor was diagnosed as a metastasis derived from the gallbladder cancer by pathology and immunohistochemistry. Expression of RCAS1, an independent unfavorable prognostic indicator in gallbladder cancer, was observed in both the gallbladder and lung tumors. However, infiltration of CD8 +T cells was only seen in the lung metastatic tumor. She has remained free of any evidence of recurrence in the 10 months and 4 years after the first surgery. The results that metastasis is solitary and infiltrated by CD8 +T cells correspond with the present clinical history.

Significance of RCAS1 antigen in hepatocellular, cholangiocellular and pancreatic carcinomas

Since receptor-binding cancer antigen expressed on SiSo cells (RCAS1) was first reported as a tumor-associated antigen of gynecologic cancer, its function and practical value as a tumor marker have been investigated in various types of carcinomas. Basic research has indicated that RCAS1 expression in cancer cells contributes to the evasion from immune surveillance and progression of carcinomas. The clinical significance of RCAS1 expression in hepatobiliary and pancreatic carcinomas has also been investigated. In this review, we summarize the clinical application of RCAS1 antigen in hepatic and pancreaticobiliary diseases. We present new data and review current knowledge about the potential of RCAS1 as a tumor marker and the relationship between RCAS1 expression and clinicopathologic parameters. We found that the clinical function of RCAS1 appeared to differ according to the type of carcinoma. In hepatocellular carcinoma, the clinical significance of histological RCAS1 expression was controversial and that of serum RCAS1 levels showed little clinical value. In pancreaticobiliary cancers, high RCAS1 expression in tissue samples was an unfavorable independent prognostic factor. Serum RCAS1 was a superior tumor marker reflecting the disease activity in biliary carcinoma. In pancreatic cancer, serum RCAS1 levels were less useful than in biliary carcinoma but may be available for genetically CA19-9-negative patients and for CA19-9-non-producing cancer. This review also offers suggestions for future studies.

The placental RCAS1 expression during stillbirth

Background: Independently of the fetal death cause the beginning and course of stillbirth is closely related with the growing cytotoxic activity at the maternal-fetal interface. RCAS1 participates in the inhibition of maternal immune response during pregnancy. The alterations of RCAS1 protein expression in placental cells seem to determine the beginning of the labor and participate in the placental abruption. The aim of the present study was to investigate RCAS1 expression in placentas obtained following stillbirths or normal term births. Methods: RCAS1 expression was evaluated by Western blot method with the use of monoclonal anti-RCAS1 antibody in 67 placental tissue samples. Pregnant women were divided into four groups according to the mode of labor onset – spontaneous or induced, and the type of labor, stillbirth or labor at term. Placental beta-Actin expression was chosen as a control protein. Relative amounts of placental RCAS1 were compared with the use of Student's t-test, whereas beta-Actin control data were compared with the use of Mann-Whitney U test. Results: The average relative amount of RCAS1 was significantly lower in women with induced stillbirths than in women with induced labor at term. Similarly, significantly lower RCAS1 placental levels were observed in patients with spontaneous stillbirths than in women with spontaneous labor at term. Significant differences in RCAS1 expression were also observed with the respect to the beginning of the stillbirth: spontaneous and induced. Lowest RCAS1 placental levels were observed in women with spontaneous stillbirth. Conclusions: These preliminary results indicate that the alterations of RCAS1 expression in the human placenta may be involved in the changes of maternal immune system that take place during stillbirth.

Expression of RCAS1 in esophageal squamous cell carcinoma is associated with a poor prognosis

Receptor-binding cancer antigen expressed on SiSO cells (RCAS1) has been reported to act as a ligand for a receptor present on normal peripheral lymphocytes and to induce apoptotic cell death. We aimed to elucidate the significance of RCAS1 expression in human esophageal squamous cell carcinomas (ESCC). RCAS1 expression was examined immunohistochemically in surgically resected esophageal carcinoma tissues from 114 patients. We also examined the relationships between RCAS1 expressions, the tumor Ki-67 indices (a marker of proliferation), and the number of CD8+ tumor-infiltrating lymphocytes (TILs). RCAS1 immunoreactivity was detected in the membranes and cytoplasm of the tumor cells. Of the 114 esophageal carcinomas, 39 (34.2%) were strongly positive for RCAS1 immunostaining on the membranes of the cancer cells, 41 (36.0%) were weakly positive, and 34 (29.8%) were negative. A comparison of RCAS1 expression and clinicopathological characteristics in all 114 patients revealed significant associations between RCAS1 expression and lymph node status (P < 0.05), and pathologic stage (P < 0.05). The survival rates of patients with RCAS1-negative tumors were significantly higher than those of patients with both RCAS1-weak positive tumors and RCAS1-strong positive ones (log-rank P < 0.05). Multivariate analysis revealed that RCAS1 positivity was an independent prognostic factor (P < 0.05). The relationship between RCAS1 expression and the numbers of CD8+ T-cells in the primary tumors revealed that RCAS1-negative tumors tended to contain more of these cells than both RCAS1-weak positive tumors and RCAS1-strong positive ones (P = 0.2495). RCAS1 may play a significant role in tumor progression via an immune escape mechanism; thus, RCAS1 expression could be used as a predictor of poor prognosis in patients with ESCC.