An expression of squamous cell carcinoma antigen 2 in peripheral blood within the different stages of esophageal carcinogenesis

The malignant transformation of esophageal mucosa is a progressive process, which includes basal cell hyperplasia, dysplasia, carcinoma in situ, and invasive esophageal squamous cell carcinoma (ESCC). The objectives of this study were to prove the relationship of squamous cell carcinoma antigen 2 (SCCA2) mRNA expression in peripheral blood with non-malignant lesion, premalignant lesion, and carcinoma of the esophagus at the same assay, as well as to evaluate whether or not SCCA2 mRNA expression in peripheral blood may be a biomarker for monitoring the premalignant lesion of the disease. The subjects consisted of 50 patients with basal cell hyperplasia, 50 patients with dysplasia, 50 patients with ESCC (12 carcinoma in situ, 38 carcinoma in invasive stage), and 50 controls who were pathologically diagnosed to be normal and whose esophageal mucosa were stained brown by iodine. All the subjects are residents of Feicheng, China, which is considered an area with a high incidence of esophageal cancer. All subjects were diagnosed by two separate histopathologists, and the expression of SCCA2 mRNA in peripheral blood was detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, SCCA2 concentration in the serum was measured using an enzyme-linked immunosorbent assay (ELISA). In the cancer group, SCCA2 mRNA expression was also detected in 20 tissues of esophageal cancer. By using the band intensity ratios of SCCA2 to beta-actin, with a positive cut-off value of >= 0.4, the positive rates of the SCCA2 mRNA expression in peripheral blood were found to be 82% (41/50), 60% (30/50), 48% (24/50), and 36% (18/50) in the cancer, dysplasia, basal cell hyperplasia, and control groups, respectively. The positive rate of the cancer group was significantly different from the three other groups (P < 0.05), and there was also a significant difference in the SCCA2 mRNA expression between the dysplasia group and the control group (chi(2)=5.769, P = 0.016). In the multinomial logistic regression analysis, the odds ratios (ORs) were 1.71 [95% confidence interval (95% CI), 0.73-3.99] in the basal cell hyperplasia group, 2.77 (95% CI, 1.14-6.71) in the dysplasia group, and 7.87 (95% CI, 2.88-21.55) in the cancer group after being adjusted for age, gender, smoking index, drinking index, and family history of esophageal cancer. The SCCA2 mRNA expression in peripheral blood was then divided into different grades according to the band intensity ratios of SCCA2 to beta-actin. By using a positive cut-off value of >= 0.4, the testing sensitivities in the basal cell hyperplasia, dysplasia, and cancer groups were found to be 48%, 60%, and 82%, respectively, with the same testing specificity at 64%. On the other hand, SCCA2 mRNA expression in peripheral blood had a 97.5% agreement with that in tissue, and there was a significant correlation between the ELISA SCCA2 levels in the serum and the SCCA2 mRNA expression levels in the peripheral blood (r = 0.80, P = 0.01). The results indicate that SCCA2 mRNA expression in peripheral blood is linked with the different stages of esophageal pathological changes, despite the fact that SCCA2 mRNA was not a biomarker for screening early esophageal cancer. This knowledge may be useful in monitoring the processes of change that occur in esophageal premalignant lesions among subjects who live in a high-incidence area.