The utility of serum receptor-binding cancer antigen expressed on SiSo cells in gastrointestinal tract cancers

1Department of Gastroenterology, Ankara University Medical School; 2Department of Gastroenterology, Ankara Education and Research Hospital; 3Department of Gastroenterology, Ankara Numune Hospital, Ankara; 4Department of Gastroenterology, Suleyman Demirel University Medical School, Isparta, Turkey Correspondence: Dr Þahin Çoban, 39 Cadde, Pembe köþk apartmaný, 1/4, 06520, Çukurambar, Balgat, Ankara, Turkey. Telephone 312-286-6803, fax 312-310-6371, e-mail scoban72@yahoo.com Received for publication January 12, 2006. Accepted January 30, 2006 Þ Çoban, H Özkan, S Köklü, et al. The utility of serum receptor-binding cancer antigen expressed on SiSo cells in gastrointestinal tract cancers. Can J Gastroenterol 2006;20(9):593-596.


PATIENTS AND METHODS
Eighty-two patients (53 men and 29 women; aged 56.12±8.72 years) with primary GI tract cancers (14 esophagus, 32 gastric and 36 colon) underwent surgery between 2003 and 2005 in the Ankara Oncology Education and Research Hospital (Ankara, Turkey) and Ankara University Medical School (Ankara, Turkey). No distant metastases were detected in any patient at the preoperative examinations. Patients who had adjuvant therapies were excluded. A reference pathologist performed histopathological examinations. The control group included 30 healthy individuals from the hospital staff aged 52.93±20.24 years.
Sera from patients with malignancies were collected before surgery. Sera were from venous blood and were frozen immediately and stored at -25°C until the measuring time. A commercial ELISA kit (Medical and Biological Laboratories Co Ltd, Japan) was used for RCAS1 assays. The same sera was also used for CEA and CA19-9 measurements. Cut-off values for RCAS1, CEA and CA19-9 were 17.5 U/mL, 4.6 ng/mL and 37.0 U/mL, respectively.
Serum RCAS1 concentrations of 17.5 U/mL or greater were defined as positive and those less than 17.5 U/mL were defined as negative. Similarly, serum CEA and CA19-9 concentrations of 4.6 ng/mL or greater and 37 U/mL or greater, respectively, were defined as positive and those less than 4.6 ng/mL and less than 37 U/mL respectively, were defined as negative. Sensitivity was defined as the number of patients diagnosed with GI tract cancers and expressing positive RCAS1, CEA or CA19-9, divided by the total number of patients diagnosed with GI tract cancers. Specificity was defined as the number of controls with negative RCAS1, CEA or CA19-9, divided by the total number of control patients. SPSS version 10.0 (SPSS Inc, USA) was used to analyze the data. Nonparametric Kruskal-Wallis test was used to analyze the variance among groups. Statistically significant differences obtained from Kruskal-Wallis analysis were further tested by Mann-Whitney U test for post hoc pairwise comparisons between groups. Pearson test was used for correlation analysis. P<0.05 was considered to be statistically significant. In all patients with GI tract cancer, RCAS1 levels were significantly higher in cases with lymph node involvement compared with lymph node-negative cases (P=0.009). However, there was no difference between cases with and without serosal involvement, vascular invasion and distant metastasis (Table 1). There was no correlation between the tumour size and RCAS1 levels (P=0.648).

Mean
Among GI tract cancers, RCAS1 had lowest and highest sensitivity for esophagus and colon cancer diagnosis, respectively ( Table 2).

DISCUSSION
In the present study, we demonstrated that patients with GI tract cancer had higher serum RCAS1 levels than healthy controls. RCAS1 had higher sensitivity than CA19-9 in all tumour groups; higher sensitivity than CEA in esophagus and stomach cancers but lower sensitivity in colon cancer. We also found that the ratio of RCAS1 positivity was greater in colon and gastric cancers compared with esophageal malignancy. Serum RCAS1 level increased significantly in GI tract tumours with lymph node involvement; however, it was not correlated with tumour grade, serosal and vascular invasion or distant metastasis. RCAS1 expression has been demonstrated with immunohistochemical analysis in esophagus, gastric and colorectal cancers (6,21,22). Its expression has been reported to be associated with aggressive tumour behaviour. Therefore, there may be a correlation between RCAS1 expression and tumour prognosis. Despite those studies demonstrating RCAS1 expression on tumour cells of the GI tract, there is only one study in the literature analyzing the serum levels of RCAS1 in GI tract tumours. Leelawat et al (22) investigated the expression of RCAS1 in colorectal cancer and measured the serum levels of the antigen. In contrast to the current study, they found that serum RCAS1 concentrations in patients with colorectal cancer were not significantly higher compared with the normal controls. They claimed that this was due to the differences in the biological features of the tumours and the limited number of serum specimens in their study. Nonetheless, cut-off values were higher in their study (greater than 22.5 U/mL in their study compared with greater than 17.5 U/mL in the present study).
Nakakubo et al (21) investigated the immunoreactivity of RCAS1 and its correlation with clinicopathological features in 95 patients who underwent surgical resection for esophageal squamous cell carcinoma. However, the expression was examined by histochemical staining rather than serum analysis. One-third of the cases were strongly positive and four of the 95 cases were negative for RCAS1 staining.
They noted that RCAS1 showed significant correlations with stage grouping (stage I and II compared with stage III and IV). However, similar to our results, there was no significant correlation between RCAS1 positivity and histopathological grading, depth of invasion and distant metastasis. In contrast to our findings, there was no correlation between RCAS1-positivity and lymph node involvement. Overall, expression of RCAS1 was associated with shorter postoperative survival.
In a study performed by Nakamura et al (6), RCAS1 positivity was detected immunohistochemically in 96% of 54 gastric cancer patients. Surgical materials were compared according to staining patterns (diffuse or not). Although staining patterns correlated with size of tumours, depth of tumour invasion, histological type and lymph node metastasis in that study, clinicopathological variables did not significantly differ between RCAS1-positive and -negative cases. Surprisingly, RCAS1 was positive in all of the normal gastric epithelial cells and the majority of benign gastric disorders; this could not be explained adequately. The authors claimed that RCAS1 was also expressed in several other normal tissues (1,2) and the biological functions of RCAS1 secreted by noncancerous tissues remains to be investigated.
CEA may be useful in the preoperative staging and postoperative follow-up of patients especially with colon cancer, but it has a variable predictive value for diagnosis in asymptomatic patients (23). We found that CEA was more specific but less sensitive than RCAS1 for GI tract cancers in the present study. On the other hand, CA19-9 was the least sensitive marker for GI tract tumours in the current study.

CONCLUSION
Serum RCAS1 levels are increased in GI tract cancers. RCAS1 and CEA had comparable sensitivity in GI tract cancers; thus, both agents increased the diagnostic efficiency of each in those tumours. Further studies are needed, including comparative analysis of pre-and postoperative serum levels to determine the prognostic significance of RCAS1.
The utility of serum RCAS1 in GI cancers