Runt-related transcription factor 3 expression in human oral squamous cell carcinomas; implication for tumor progression and prognosis.

Runt-related transcription factor 3 (RUNX3) is a tumor suppressor factor of gastric cancer and appears to be an important component of the transforming growth factor-beta (TGF-beta)-induced tumor suppression pathway. This study aimed to analyze the expression of the RUNX3 protein in human oral normal epithelia, dysplasia and squamous cell carcinomas (SCCs), comparing it with clinicopathological profiles. Western blot analysis revealed the RUNX3 protein as a single band at 44kDa in oral non-neoplastic mucosa and SCC. The expression of RUNX3 protein was also examined in 10 normal epithelia, 51 dysplasias and 108 oral SCCs. The labeling indices (LIs) of RUNX3, Ki-67, P21, P27 and the apoptotic index (AI) were evaluated using immunohistochemistry and the TUNEL method. The LI of RUNX3 was 7.7+/-1.6 in the normal epithelia, 20.8+/-2.7 in the dysplasias and 9.0+/-1.3 in the SCCs. The LI of RUNX3 was significantly highest in the dysplasias, followed by the SCCs (p<0.05) and normal epithelia (p<0.05). The RUNX3 LI correlated with the histological differentiation of SCCs, being the highest in the well differentiated SCCs (p<0.01). In addition, RUNX3 expression was significantly related to the lower Ki-67 LI, but not to LI of P21 and P27, and AI in the SCCs. The survival rate was significantly lower in the patients with lower RUNX3 expression (<5%) than in those with higher expression (5%) (p<0.05). These results indicate that the expression of RUNX3 is correlated with histological differentiation, and inversely with cellular proliferation of the oral SCCs, and might be a new prognostic marker in the patients with oral SCC.

Expression of RUNX3 protein in human esophageal mucosa and squamous cell carcinoma.

Runt-related transcriptional factor gene 3 (RUNX3) belongs to the runt domain family of transcriptional factors that plays an important role during normal tissue development and in tumorigenesis in several organs. This study examined the expression of RUNX3 protein in human esophageal mucosa and squamous cell carcinoma in comparison with clinicopathological profiles. Western blot analysis and RT-PCR revealed that both RUNX3/P44 and P27, but not P46, were expressed in all three human esophageal squamous cell carcinoma (SCC) cell lines, as well as in three pairs of esophageal SCC cell lines and the corresponding nontumoral mucosa specimens. RUNX3 expression was shown in prickle and functional cell layer cells in normal esophageal mucosa. On the other hand, immunoreactivity was seen only in carcinoma cells around the cancer pearls. RUNX3 expression was significantly higher in the 19 well-differentiated SCCs than in the 56 moderately or 69 poorly differentiated SCCs (p < 0.01). The 3-year survival rate was significantly lower in the 29 patients with lower RUNX3 expression than in the 37 patients with higher expression (p = 0.0003). These results indicated that RUNX3 protein might play an important role in cellular differentiation in both esophageal mucosa and SCC. The expression correlated with the patients' prolonged survival, implying a tumor suppressive effect in esophageal SCCs.