Publications (19)74.08 Total impact
-
Article: Clinical significance of RCAS1 as a biomarker of ovarian cancer.
[show abstract] [hide abstract]
ABSTRACT: 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.Oncology Reports 03/2007; 17(3):623-8. · 1.84 Impact Factor -
Article: Clinical significance of RCAS1 as a biomarker of uterine cancer.
[show abstract] [hide abstract]
ABSTRACT: 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. 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. 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-alpha 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). 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.Gynecologic Oncology 12/2006; 103(3):924-31. · 3.89 Impact Factor -
Article: Receptor-binding cancer antigen expressed on SiSo cells can be detected in metastatic lymph nodes from gastrointestinal cancers.
[show abstract] [hide abstract]
ABSTRACT: To investigate the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) in metastatic lymph nodes from gastrointestinal cancer. Metastatic lymph nodes from gastrointestinal cancer were detected for RCAS1 by immunohistochemical staining and mRNA in situ hybridization. A total of 102 metastatic lymph nodes from bile duct, gastric, colon and pancreatic cancer were investigated for RCAS1 expression. The immunoreactivity of RCAS1 was identified in 100% of metastatic lymph nodes. Both local and distant metastatic lymph nodes showed RCAS1 expression. On the contrary, specimens of non-cancerous lymph nodes were negative for RCAS1. The result of mRNA in situ hybridization was also confirmed by the finding of immunohistochemical staining. RCAS1 mRNA was detected in all tumor cells that metastasized to lymph nodes. All metastatic lymph nodes express RCAS1 in tumor cells at both mRNA levels, and RCAS1 that should be used as a complementary factor for identification of metastatic lymph nodes from gastrointestinal cancers.World Journal of Gastroenterology 11/2005; 11(38):6014-7. · 2.47 Impact Factor -
Article: Invasive potency related to RCAS1 expression in uterine cervical cancer.
[show abstract] [hide abstract]
ABSTRACT: 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. 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. 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. RCAS1 may contribute to acquisition of malignant uterine cervical phenotypic characteristics including invasion, metastasis, and tumor growth via connective tissue remodeling.Gynecologic Oncology 10/2005; 99(1):189-98. · 3.89 Impact Factor -
Article: Association between RCAS1 expression and microenvironmental immune cell death in uterine cervical cancer.
[show abstract] [hide abstract]
ABSTRACT: : The presence of regional lymph node metastasis is one of the prognostic factors for uterine cervical cancer. The development of metastasis requires that cancer cells avoid lymphocyte attack. Impaired lymphocyte function is mediated by apoptotic factors including receptor-binding cancer antigen expressed on SiSo cells (RCAS1), Fas ligand (FasL), and tumor necrosis factor-alpha (TNF-alpha). Our aim was to evaluate the association between expression of these factors and microenvironmental lymphocyte apoptosis in this disease. : Immunohistochemical methods were used to determine the relationship between the expression of RCAS1, FasL, and TNF-alpha, and the number of apoptotic lymphocytes in primary lesions and metastatic lymph nodes in patients with cervical cancer. : Expression of these apoptosis-inducing molecules was quite different in primary tumors and metastatic lymph nodes: RCAS1 expression in lymph nodes was significantly higher than that in primary lesions (P < 0.0001), whereas FasL and TNF-alpha expressions at these two locations were not significantly different. The number of cells with positive expression of RCAS1, but not of FasL or TNF-alpha, was significantly correlated with the number of apoptotic lymphocytes in uterine cervix and metastatic lymph nodes (P < 0.0001 for both). : RCAS1 expression may be related to tumor cell evasion of immune surveillance via induction of lymphocyte apoptosis in primary lesions and metastatic lymph nodes in uterine cervical cancer.Gynecologic Oncology 07/2005; 97(3):772-9. · 3.89 Impact Factor -
Article: A novel mechanism in suppression of erythropoiesis during inflammation: a crucial role of RCAS1.
[show abstract] [hide abstract]
ABSTRACT: A novel human tumor-associated antigen, receptor-binding cancer antigen expressed on SiSo cells (RCAS1), induces apoptosis in normal human erythroid progenitor cells, which express putative RCAS1 receptors. In the present study, we investigated a possible role of RCAS1 produced by human peripheral blood monocytes (CD14-positive cells) and monocyte-derived macrophages. RCAS1 was immunohistochemically detected in monocytes as well as macrophages. When macrophages were stimulated with lipopolysaccharide (LPS), the expression of RCAS1 was remarkably enhanced. An increased production of RCAS1 mRNA was observed in LPS-stimulated macrophages by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Soluble RCAS1 molecules were only detected in the culture supernatants obtained from LPS-stimulated macrophages. Moreover, LPS-stimulated macrophages induced cell death of erythroid progenitor cells through RCAS1 production. These results suggest that macrophages may negatively regulate erythropoiesis at least in part through the production of RCAS1 molecules, and this may contribute to the pathogenesis of the anemia seen in patients with inflammatory disorders.European Journal Of Haematology 06/2005; 74(5):365-73. · 2.61 Impact Factor -
Article: Growth retardation and dyslymphopoiesis accompanied by G2/M arrest in APEX2-null mice.
[show abstract] [hide abstract]
ABSTRACT: APEX2/APE2 is a secondary mammalian apurinic/apyrimidinic endonuclease that associates with proliferating cell nuclear antigen (PCNA), and the progression of S phase of the cell cycle is accompanied by its expression. To determine the biologic significance of APEX2, we established APEX2-null mice. These mice were about 80% the size of their wild-type littermates and exhibited a moderate dyshematopoiesis and a relatively severe defect in lymphopoiesis. A significant accumulation of both thymocytes and mitogen-stimulated splenocytes in G(2)/M phase was seen in APEX2-null mice compared with the wild type, indicating that APEX2 is required for proper cell cycle progression of proliferating lymphocytes. Although APEX2-null mice exhibited an attenuated immune response against ovalbumin in comparison with wild-type mice, they produced both antiovalbumin immunoglobulin M (IgM) and IgG, indicating that class switch recombination can occur even in the absence of APEX2.Blood 01/2005; 104(13):4097-103. · 9.90 Impact Factor -
Article: Serum levels of soluble molecules associated with evasion of immune surveillance: a study in biliary disease.
[show abstract] [hide abstract]
ABSTRACT: Biliary carcinoma cells produce the transmembrane proteins, Fas, FasL, and RCAS1. It has been demonstrated that the Fas/FasL and RCAS1 systems induce apoptosis of activated immune cells and that the soluble isoforms of these proteins (sFas, sFasL, and sRCAS1) also exhibit this function. We measured serum levels of these soluble-types in patients with biliary disease by ELISA and investigated their clinical significance. In some cases of cholangitis and autoimmune biliary disease, serum sFasL values were over 0.1 ng/ml but the protein was undetectable in any patients with biliary carcinoma. sFas levels were significantly higher in the autoimmune disease (mean, 6.83 ng/ml) and cancer (mean, 6.42 ng/ml) groups than in the cholangitis group (mean, 4.23 ng/ml) and normal controls (mean, 2.93 ng/ml). However, the sFas values in malignancy did not correlate with the progression of clinical stage. The percentage positive for serum sRCAS1 was 9.7% in benign disease but was 63.4% in cancer. Our data suggest that serum sFasL in biliary disease may be derived predominantly from activated immune cells and not from cancer cells and that autoimmune biliary disease may be mediated by the Fas/FasL apoptotic system. sRCAS1 is highly tumor-specific and may be of value in the diagnosis of malignancy.Liver international: official journal of the International Association for the Study of the Liver 09/2004; 24(4):330-4. · 3.82 Impact Factor -
Article: Expression of human tumor-associated antigen RCAS1 in adult T-cell leukemia/lymphoma.
[show abstract] [hide abstract]
ABSTRACT: In human cancer, RCAS1 (the receptor-binding cancer antigen expressed on SiSo cells) on the surface of various kinds of tumor cells reportedly induces the apoptosis of T-cells and natural killer cells, resulting in evasion of the immune system. In the present study, an immunohistochemical analysis of RCAS1 expression was performed with lymph node specimens obtained from patients with adult T-cell leukemia/lymphoma (ATLL). Positive staining was seen in 15 (75%) of 20 cases and in all cases of patients with short survival times. In the cases of B-cell lymphomas, positive staining was seen in only 1 (13%) of 8 cases. These findings indicate that expression of RCAS1 may be associated with the evasion from immune surveillance of cells infected with human T-lymphotropic virus type I, resulting in the development of overt leukemia/lymphoma. Determination of RCAS1 expression may be useful for predicting the prognosis of patients with ATLL.International Journal of Hematology 06/2004; 79(4):340-4. · 1.27 Impact Factor -
Article: Expression of RCAS1 in human gastric carcinoma: a potential mechanism of immune escape.
[show abstract] [hide abstract]
ABSTRACT: RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) inhibits the in vitro growth of receptor-expressing cells and induces apoptosis, which may contribute to the ability of tumor cells to evade host immune surveillance. In this study, we investigated RCAS1 expression in gastric cancer and precancerous lesions by immunohistochemical means. We then analyzed the relationship between RCAS1 expression and clinicopathological variables, and examined whether RCAS1 expression is associated with infiltration of tumor-infiltrating lymphocytes (TILs) and apoptosis of TILs. Of 54 gastric cancers analyzed, RCAS1 expression was positive in 52 (96%) of them. The expression pattern of RCAS1 in gastric cancer cells could be classified as granular staining either enriched in the glandular side of the cytoplasm with polarity (P pattern) or scattered diffusely in the cytoplasm and on the cell membranes (D pattern). Nineteen of 39 intestinal-type carcinomas (49%) showed the P pattern, and all of 13 diffuse type carcinomas (100%) showed the D pattern. In contrast, all RCAS1-positive specimens of gastric adenoma and metaplastic mucosa were of the P pattern. The D pattern of gastric cancers was more frequently recognized in carcinomas with large size (P < 0.01), in those with regional lymph node metastasis (P < 0.05) and in those that had invaded beyond the submucosa (P < 0.01), compared with the P pattern. On the same sections, significantly less TILs were identified in RCAS1-positive areas than RCAS1-negative areas. Furthermore, the rate of apoptosis of TILs was significantly higher in RCAS1-positive areas than in RCAS1-negative areas. The expression and distribution of RCAS1 may be involved in malignant transformation, tumor progression, histological type and tumor escape from host immune surveillance in gastric cancer.Cancer Science 03/2004; 95(3):260-5. · 3.33 Impact Factor -
Article: Differential chemokine, chemokine receptor, cytokine and cytokine receptor expression in pulmonary adenocarcinoma: diffuse down-regulation is associated with immune evasion and brain metastasis.
[show abstract] [hide abstract]
ABSTRACT: Pulmonary adenocarcinoma is frequently associated with brain metastasis at some stage during the disease course. Host immunity, particularly T cell immunity, plays an important role in the clinicopathological features of carcinoma proliferation and metastasis. Cytokines and chemokines are members of a family of small secreted proteins. The relationships between the cytokines and cytokine receptor (R), and between chemokines and chemokine R are important determinants of selectivity in local immunity. RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) and Fas ligand (FasL) are present in neoplastic cells, induce apoptosis of NK/T cells, and play a role in immune evasion. To investigate differences in host immunity between pulmonary adenocarcinoma with and without brain metastasis, we performed gene expression profiling, using chemokine, chemokine R, cytokine and cytokine R DNA chips. In addition, to assess the extent of immune evasion, we examined the expression of RCAS and FasL. We studied five cases of pulmonary adenocarcinoma with brain metastasis (meta) and five cases without brain metastasis (non-meta). The brain meta cases exhibited diffuse down-regulated profiles, in comparison with normal non-carcinomatous lungs, which were used as controls. Non-meta cases also displayed diffuse down-regulation, however the degree was variable. Expression of RCAS and FasL was detected in almost all cases, but was stronger in meta than non-meta cases. Our findings suggested that tumor cells evaded host immunity. In the gene tree analysis, brain meta cases and non-meta cases exhibited distinct clustering. Brain meta cases exhibited significantly lower expression of interleukin 13 receptor alpha2 (IL-13Ralpha2) than non-meta cases. The reduction of IL-13Ralpha2 expression was confirmed by RT-PCR. Immunohistochemically, non-meta adenocarcinoma cells frequently expressed IL-13Ralpha2, however, IL-13Ralpha2 expression was rare or weak in adenocarcinomas with meta. Our results suggested that, in addition to immune evasion, the characteristics of the adenocarcinoma tumors themselves were important for brain metastasis. However, our study demonstrated the enormous potential of gene expression profiling in clarifying the pathogenesis of brain metastasis in pulmonary adenocarcinoma.International Journal of Oncology 11/2003; 23(4):965-73. · 2.40 Impact Factor -
Article: Clinical significance of serum RCAS1 levels detected by monoclonal antibody 22-1-1 in patients with cholangiocellular carcinoma.
[show abstract] [hide abstract]
ABSTRACT: The tumor-associated antigen, RCAS1, has been reported to be expressed in various types of cancer, including cholangiocarcinoma. We measured serum RCAS1 levels in patients with intrahepatic cholangiocellular carcinoma (CCC) and other hepatobiliary diseases, and examined the clinical significance of serum RCAS1 as a tumor marker. Sera collected from the patients and healthy volunteers were used for ELISA for RCAS1. The values of RCAS1 for CCC patients were compared to those of other tumor marker proteins. Serum RCAS1 levels exceeded the normal limit in a high percentage (73.9%) of CCC patients. The positivity rate was higher than those of CA19-9 and CEA. No correlation was found between the RCAS1 and CA19-9 concentrations. Serum RCAS1 was positive in many cases that were negative for CA19-9. Surgical resection of CCC reduced the RCAS1 level to within the normal range. On the other hand, serum RCAS1 levels were elevated in very few cases of benign hepatobiliary disease. As a tumor marker in CCC, RCAS1 is, at least, of complementary value to CA19-9 and CEA. Measuring serum RCAS1 contributes to the diagnostic accuracy, and is useful for estimating tumor progression or therapeutic effect.Journal of Hepatology 11/2003; 39(4):559-63. · 9.26 Impact Factor -
Article: Expression of tumor-associated membrane antigen, RCAS1, in human colorectal carcinomas and possible role in apoptosis of tumor-infiltrating lymphocytes.
[show abstract] [hide abstract]
ABSTRACT: RCAS1, a novel tumor-associated antigen, is expressed in advanced human neoplasias including uterine and ovarian carcinomas. RCAS1 protein was indicated to induce cell cycle arrest and apoptosis of cultured human lymphoid and myeloid cell lines and normal lymphocytes. In the present study, we investigated the expression and prognostic value of RCAS1 in 58 patients with colorectal carcinomas. RCAS1 protein was detected by immunoperoxidase staining using a mouse monoclonal anti-RCAS1 antibody (22-1-1 antibody). Immunohistochemical examination showed expression of RCAS1 in 75% of colorectal carcinomas with lymph node metastases (n = 24), whereas it was present in only 41% of tumors without metastases (n = 34, P <.05). Patients with RCAS1-positive tumors showed a significantly poorer prognosis than those negative for RCAS1 (P <.05). Multivariate analysis using the Cox regression model indicated that RCAS1 positivity was an independent negative predictor for survival (P =.0300; risk ratio, 0.496). In addition, apoptotic cells of tumor-infiltrating lymphocytes were examined using nonradioactive in situ nick translation in paraffin-embedded sections. The proportion of apoptotic tumor-infiltrating lymphocytes was significantly higher in RCAS1-positive colorectal carcinomas (11.2 +/- 1.0) than in RCAS1-negative tumors (7.9 +/- 1.0, P <.05). Our results suggest that overexpression of RCAS1 may negatively affect the prognosis of human colorectal carcinomas and that RCAS1 may play a role in tumor immune privilege in vivo.Modern Pathology 08/2003; 16(7):679-85. · 4.79 Impact Factor -
Article: Expression of apoptosis-associated protein RCAS1 in macrophages of histiocytic necrotizing lymphadenitis.
[show abstract] [hide abstract]
ABSTRACT: Receptor-binding cancer antigen expressed on SiSo cells (RCAS1), which is recognized by the 22-1-1 monoclonal antibody (MoAb) against human uterine adenocarcinoma cell line SiSo, has been identified on various kinds of cancer cells. RCAS1 appears to be an apoptosis-associated protein that induces apoptosis in activated T-cells and erythroid progenitor cells. We previously demonstrated that monocytes/macrophages express RCAS1. In the present study, we investigated RCAS1 expression by 22-1-1 MoAb in histiocytic necrotizing lymphadenitis (HNL), which is characterized by necrotic lesions consisting of T-cells undergoing apoptosis and macrophages in proliferation. Expression of RCAS1 was analyzed by immunohistochemical staining in 9 cases of HNL and in 9 cases of reactive lymphadenitis used as a control. The ratio of RCAS1+ cells to CD68+ cells (monocytes/macrophages) was significantly higher in the patients with HNL than in the patients with reactive lymphadenitis (P = .0002; paired t test). Our findings suggest that RCAS1 expressed on macrophages may play an important role in the induction of activated T-cell apoptosis in cases of HNL.International Journal of Hematology 06/2003; 77(4):359-63. · 1.27 Impact Factor -
Article: Expression and diagnostic evaluation of the human tumor-associated antigen RCAS1 in pancreatic cancer.
[show abstract] [hide abstract]
ABSTRACT: Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is one of the membrane molecules expressed on human cancer cells and is presumed to play a protective role for tumor cells against immune surveillance by inhibition of clonal expansion and induction of cell death in immunocytes. To address whether RCAS1 is expressed in pancreatic cancer and whether serologic diagnostic evaluation is useful compared with that of carbohydrate antigen 19-9 (CA19-9) and soluble Fas ligand. Immunohistochemical expression of RCAS1 was examined by staining with a 22-1-1 monoclonal antibody, and serum RCAS1 concentrations were determined by an enzyme-linked immunosorbent assay in 20 cases of ductal adenocarcinoma of the pancreas and other pancreatic diseases. Immunohistochemically, RCAS1 detection occurred in 100% (20/20) of ductal adenocarcinoma of the pancreas cases, 100% (6/6) of intraductal papillary-mucinous adenoma of the pancreas cases, and 40% (2/5) of chronic pancreatitis cases. RCAS1 was found in the cytoplasm of cancer cells and ductal cells. Serum RCAS1 concentrations in patients with ductal adenocarcinoma of the pancreas were significantly higher than those in patients with chronic pancreatitis (p < 0.0001), acute pancreatitis (p < 0.005), and autoimmune pancreatitis (p < 0.001). RCAS1 concentrations in patients with intraductal papillary-mucinous adenoma of the pancreas were also significantly higher than those in patients with chronic pancreatitis (p < 0.05) and autoimmune pancreatitis (p < 0.05). Positive serum RCAS1 samples (concentration, > or = 10 U/mL) were found most often in cases of pancreatic neoplasm (80% [16/20], ductal adenocarcinoma of the pancreas; and 60% [3/5], intraductal papillary-mucinous adenoma of the pancreas). By contrast, in cases of pancreatic inflammatory diseases, raised concentrations occurred in 9.4% (3/32) of chronic pancreatitis cases, none (0/6) of acute pancreatitis cases, and none (0/8) of autoimmune pancreatitis cases. The sensitivity of CA19-9 for ductal adenocarcinoma of the pancreas was 75% and the specificity was 73.1% compared with chronic pancreatitis. On the other hand, the sensitivity of RCAS1 for ductal adenocarcinoma of the pancreas was 80% and the specificity was 96.2% compared with chronic pancreatitis. The specificity of RCAS1 for chronic pancreatitis was higher than that of CA19-9. Serum soluble Fas ligand concentrations were not considerably different among these patients. RCAS1 was highly expressed in ductal adenocarcinoma of the pancreas, and serum RCAS1 concentrations in patients with ductal adenocarcinoma of the pancreas were significantly higher than those in patients with other inflammatory pancreatic diseases. Our results indicate that serum RCAS1 concentrations could be a new marker in screening procedures for pancreatic cancer.Pancreas 01/2003; 26(1):49-55. · 2.39 Impact Factor -
Article: Expression and Diagnostic Evaluation of the Human Tumor-Associated Antigen RCAS1 in Pancreatic Cancer
[show abstract] [hide abstract]
ABSTRACT: Introduction: Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is one of the membrane molecules expressed on human cancer cells and is presumed to play a protective role for tumor cells against immune surveillance by inhibition of clonal expansion and induction of cell death in immunocytes. Aims: To address whether RCAS1 is expressed in pancreatic cancer and whether serologic diagnostic evaluation is useful compared with that of carbohydrate antigen 19-9 (CA19-9) and soluble Fas ligand. Methodology: Immunohistochemical expression of RCAS1 was examined by staining with a 22-1-1 monoclonal antibody, and serum RCAS1 concentrations were determined by an enzyme-linked immunosorbent assay in 20 cases of ductal adenocarcinoma of the pancreas and other pancreatic diseases. Results: Immunohistochemically, RCAS1 detection occurred in 100% (20/20) of ductal adenocarcinoma of the pancreas cases, 100% (6/6) of intraductal papillary-mucinous adenoma of the pancreas cases, and 40% (2/5) of chronic pancreatitis cases. RCAS1 was found in the cytoplasm of cancer cells and ductal cells. Serum RCAS1 concentrations in patients with ductal adenocarcinoma of the pancreas were significantly higher than those in patients with chronic pancreatitis (p < 0.0001), acute pancreatitis (p < 0.005), and autoimmune pancreatitis (p < 0.001). RCAS1 concentrations in patients with intraductal papillary-mucinous adenoma of the pancreas were also significantly higher than those in patients with chronic pancreatitis (p < 0.05) and autoimmune pancreatitis (p < 0.05). Positive serum RCAS1 samples (concentration, ≥10 U/mL) were found most often in cases of pancreatic neoplasm (80% [16/20], ductal adenocarcinoma of the pancreas; and 60% [3/5], intraductal papillary-mucinous adenoma of the pancreas). By contrast, in cases of pancreatic inflammatory diseases, raised concentrations occurred in 9.4% (3/32) of chronic pancreatitis cases, none (0/6) of acute pancreatitis cases, and none (0/8) of autoimmune pancreatitis cases. The sensitivity of CA19-9 for ductal adenocarcinoma of the pancreas was 75% and the specificity was 73.1% compared with chronic pancreatitis. On the other hand, the sensitivity of RCAS1 for ductal adenocarcinoma of the pancreas was 80% and the specificity was 96.2% compared with chronic pancreatitis. The specificity of RCAS1 for chronic pancreatitis was higher than that of CA19-9. Serum soluble Fas ligand concentrations were not considerably different among these patients. Conclusions: RCAS1 was highly expressed in ductal adenocarcinoma of the pancreas, and serum RCAS1 concentrations in patients with ductal adenocarcinoma of the pancreas were significantly higher than those in patients with other inflammatory pancreatic diseases. Our results indicate that serum RCAS1 concentrations could be a new marker in screening procedures for pancreatic cancer.Pancreas 12/2002; 26(1):49-55. · 2.39 Impact Factor -
Article: The tumor-associated antigen, RCAS1, can be expressed in immune-mediated diseases as well as in carcinomas of biliary tract.
[show abstract] [hide abstract]
ABSTRACT: RCAS1, which is recognized by the specific antibody 22-1-1, was first identified as a tumor-associated antigen in gynecological carcinomas. RCAS1 is the ligand of a putative receptor present on lymphocytes, the expression of which is enhanced by lymphocyte activation. RCAS1 inhibits the growth of receptor-bearing cells and induces apoptotic death. Here we examined RCAS1 expression in biliary diseases. RCAS1 expression was immunohistochemically examined on tissue samples. Apoptotic death was analyzed by DNA fragmentation detection method. RCAS1 production by cell lines was investigated by flow cytometry, enzyme-linked immunosorbent assay, and reverse transcription-polymerase chain reaction. All cholangiocarcinoma cell lines examined clearly expressed RCAS1 at both the protein and RNA level. Immunohistochemically, RCAS1 was expressed in a high percentage of biliary adenocarcinomas (85.9% of intrahepatic cholangiocarcinomas, 96.4% of extrahepatic cholangiocarcinomas and gallbladder carcinomas). Apoptotic tumor-infiltrating lymphocytes could be found in these specimens. RCAS1 expression was frequently detected also in biliary epithelial cells in cases of immune-mediated cholangitis (74.2% in primary biliary cirrhosis, 66.6% in graft-versus-host disease), although the staining pattern for RCAS1 was different compared with cancer cells. RCAS1 is highly expressed not only in cancer cells but also in non-tumor bile duct cells subjected to immune attack.Journal of Hepatology 07/2002; 36(6):786-92. · 9.26 Impact Factor -
Article: RCAS1 expression in immune-mediated liver diseases.
Journal of Clinical Gastroenterology 04/2002; 34(3):286-7. · 3.16 Impact Factor -
Article: RCAS1 expression: a potential prognostic marker for adenocarcinomas of the lung.
[show abstract] [hide abstract]
ABSTRACT: RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a new tumor-associated antigen recognized by 22-1-1 monoclonal antibody. RCAS1 expressed on human cancer cells acts as a ligand for a putative receptor present on peripheral lymphocytes. RCAS1 has been shown to inhibit the in vitro growth of receptor-expressing cells and to induce apoptosis, which may contribute to the ability of tumor cells to evade host immune surveillance. In this study, we evaluated the prognostic significance of RCAS1 expression in primary lung adenocarcinomas. Immunohistochemical analysis was performed on tissue specimens surgically obtained from 102 patients with primary lung adenocarcinomas. Then, the association of RCAS1 expression with clinicopathological variables and prognosis of patients were analyzed. Of 102 lung adenocarcinomas, positive RCAS1 expression was observed in 82 cases (80%). There was no correlation between RCAS1 expression and clinicopathological variables. In 70 potentially curatively resected lung adenocarcinomas, patients with RCAS1-positive tumors had a significantly shorter survival than those with RCAS1-negative tumors (p = 0.02), and RCAS1 expression was a significant and independent prognostic factor by multivariate analysis (p = 0.03). These results indicate that RCAS1 expression predicts prognosis in patients with lung adenocarcinomas, and this new antigen could be a novel tumor marker which reflects the clinical outcome of lung cancers.Oncology 02/2002; 62(4):333-9. · 2.27 Impact Factor
Top co-authors
Top Journals
- Gynecologic Oncology (3)
- Journal of Hepatology (2)
- International Journal of Hematology (2)
- Blood (1)
- Oncology (1)
Institutions
-
2002–2007
-
Kyushu University
- • Department of Obstetrics and Gynecology
- • Medical Institute of Bioregulation - MIB Hospital
- • Graduate School of Medical Sciences
Fukuoka-shi, Fukuoka-ken, Japan
-
