Expression of RUNX3 in salivary adenoid cystic carcinoma: Implications for tumor progression and prognosis

Abstract

Runt-related transcription factor-3 (RUNX3), being a tumor suppressor gene in gastric cancer, plays an important role in inhibiting cellular growth by participating in the transforming growth factor-beta-dependent apoptosis. The aim of this study was to determine the expression of RUNX3 in normal salivary glands and adenoid cystic carcinomas (ACCs), comparing the results with clinicopathological factors and patient survival. The quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis and Western blot analysis revealed the expression of RUNX3 both in normal salivary glands and ACCs. Nuclear and cytoplasmic immunoreactivities against RUNX3 in ductal luminal cells and acinous cells, but immunonegative in myoepithelial cells, were detected in normal salivary glands. In ACC, the RUNX3 immunostaining was shown in the cytoplasm of tumor cells; however, no nuclear location of RUNX3 was found. Lower RUNX3 expression showed significant correlation to distant metastasis and histological growth pattern (P = 0.009 and P = 0.025, respectively). On univariate analysis, low level of RUNX3 immunolabeling (P = 0.012), stage T4 (P = 0.017), lymph node involvement (P = 0.007), and distant metastasis (P < 0.001) were significantly associated with decreased overall survival. Multivariate analysis showed only distant metastasis had an independent prognostic effect on overall survival (P = 0.043). Our results demonstrate the expression of RUNX3 in normal salivary glands and salivary ACCs. The low level of RUNX3 protein in salivary ACCs might play a pivotal role in tumor progression and have prognostic values in ACCs.

The incidence of MYB gene breaks in adenoid cystic carcinoma of the salivary glands and its prognostic significance

“…adenoid cystic carcinoma is a salivary tumour in which genetic abnormalities were studied. Jian Fen He 15 and sasahira 16 found a negative correlation between the expression of the rUNX3 suppressor gene and its prognosis. This tumour, like some other salivary carcinomas, is associated with increased but prognostically irrelevant expression of the c-kit oncoprotein and eGFr (ref.…”

miR-21 regulates tumor progression through the miR-21-PDCD4-Stat3 pathway in human salivary adenoid cystic carcinoma

“…4,5 Although the 5-year survival rate is high for patients with SACC, probably because of the slow growth of the tumor, the 10-and 15-year prognoses are poor because of the frequent local recurrences and distant metastases. [6][7][8] Although multiple genetic and epigenetic alterations have been detected in SACC, 3,[9][10][11][12][13] the precise molecular mechanisms of progression and metastasis of SACC remain unknown.…”

“…1,2 SACC is characterized by slow but aggressive growth, nerve and blood vessel invasion, multiple recurrences, and distant metastases. [3][4][5] Lung metastasis and nerve metastasis are the biological characteristics of SACC. [6][7][8] It has been reported that the incidence of SACC with distant metastasis ranged from 35 to 50% of all cases.…”

Unfavorable clinical implications for hypermethylation of RUNX3 in patients with salivary gland adenoid cystic carcinoma

“…Meanwhile, in the cox multivariate survival analysis, there was significant association between rUnX3 methylation and overall survival (p=0.011). therefore, RUNX3 may be a candidate as a prognostic marker and a molecular therapeutic target for salivary Acc, providing a new approach for the diagnosis and treatment of Acc (58). this trend warrants further investigation and statistical evaluation in a larger series of patients with a longer follow-up period.…”