Purpose: The canonical signaling pathway for the transforming growth factor-beta (TGF-β) family is through the Smad proteins which are pivotal intracellular mediators of TGF-β family members. Recently, disruption of the TGF-β pathway in cancer has been demonstrated at the level of the Smad signal transducers. In this study, we examined Smad4 and Smad7 expression in gastric carcinomas to elucidate their role in tumor progression.
Methods: The immunohistochemical expression of Smad4 and Smad7 was evaluated in 151 surgically resected samples of gastric adenocarcinoma in order to examine their correlation with clinicopathologic findings and patients' survival.
Results: Smad4 and Smad7 expression (low, moderate or strong) was observed in 86.7% (131/151) and 33.1% (50/151) of gastric adenocarcinoma tumor samples, respectively. Our results revealed that the loss of Smad4 expression correlated significantly with the intestinal type, male sex, depth of tumor and poor survival. Smad7 expression was significantly more frequent in intestinal type and well differentiated gastric adenocarcinomas and significantly correlated with the duration of disease-free survival.
Conclusion: Smad signal transducers are considered as important molecules in tumor development and progression and the evaluation of their expression in human gastric cancer could be useful in selecting stage I patients who should be considered as candidates for adjuvant chemotherapy.