Background Gastric carcinoma (GC) is the tenth most prevalent cancer in both sexes in Egypt. Many pathways have been investigated regarding pathogenesis of GC, including epithelial-mesenchymal transition (EMT) pathway. In view of multiplicity of carcinogenic pathways, poor survival and chemotherapy resistance detected in GC patients, more analysis of these pathways is required for better molecular selection of patients, prediction of prognosis and developing new therapeutic targets. Down-regulation of E-Cadherin is an important EMT stage. RORα is a tumor suppressor gene, expressed in normal epithelial tissues and reduced in a variety of human cancers. Knocking down of RORα; increase cell proliferation, EMT, migration, and invasion. LAPTM4B is a protooncogene and it has been suggested to be strictly associated with EMT induction. Therefore, this work aims to investigate the role of RORα, LAPTM4B and E-Cadherin and its relationship to prognosis of GC. Methods This is a retrospective study where the standard immunohistochemical technique was done to assess the expression of RORα, LAPTM4B and E-Cadherin in 167 cases of chronic gastritis (control group) and 73 primary gastric carcinomas (51 of them have available adjacent non tumor tissue). Results Low RORα and high LAPTM4B expression in GC cases were associated with unfavorable prognostic factors such as positive lymph nodes, and high tumor budding. E-Cadherin Heterogeneous staining was associated with poor prognostic pathological criteria, such as diffuse type GC and high tumor budding. In GC, there was significant co parallel correlation between RORα and E-Cadherin expression while LAPTM4B showed inverse correlation with E-Cadherin expression. Low RORα, high LAPTM4B, and negative or heterogeneous E-Cadherin were the most common immunohistochemical profile in GC cases. Low RORα expression showed poor prognostic impact on overall patient survival. Conclusions Low RORα H-score and increased expression of LAPTM4B were significantly associated with unfavorable prognostic parameters of GC which may indicate their crucial role in tumor aggressiveness. The predominance of low RORα, high LAPTM4B and heterogeneous or negative E-Cadherin immunohistochemical profile in GC cases with unfavorable pathological parameters suggested that this profile may predict tumor behavior and this profile could be linked to EMT molecular subtype of GC

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