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 > or = 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 > or = 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.