Comparative Study of ERK1/2, Bcl2, and Sorcin with Clinicopathological Characteristics of Gastric carcinoma: Tubular Adenocarcinoma Vs Signet Ring Cell Carcinoma.

[BACKGROUND AND OBJECTIVE] Altered expression of tissue-specific tumor markers is associated with clinicopathological factors and poor clinical outcomes in Gastric Cancer (GC). However, the markers have been scarcely explored in the context of the distinct GC subtypes, which are crucial for assessing treatment response.  This study explores the nuanced differences between gastric tubular adenocarcinoma (TA) and signet ring cell carcinoma (SRCC), focusing on the correlation of ERK1/2, Bcl2, and Sorcin expression. The aim is to identify potential differences between the subtypes and assess the prognostic value of the markers in relation to clinicopathological outcomes.

[METHODS] Immunohistochemistry evaluated the ERK1/2, Bcl2 and Sorcin expression in 78 patients (TA=37, SRCC=33; other=8) diagnosed with advanced non-metastatic GC. Descriptive statistics and correlations were assessed between the proteins and clinicopathological features. Overall survival and hazard risk (HR) were determined using Kaplan-Meier and Cox proportional hazard analyses.

[RESULTS] Higher ERK1/2 (66%) and lower Bcl2 (51%) expression was demonstrated in SRCC, whereas the opposite trend was noted in TA cases. On the contrary, Sorcin expression was high in both, however, predominant in SRCC (66%). Notably, post-NACT, the expression of these proteins was elevated. Significant difference in survival between TA (22±3.03 months) and SRCC (12±1.62 months) (p=0.007) was observed. In SRCC, higher ERK1/2, Sorcin, and low Bcl2 expressions were associated with shorter survival with HR>1 (p<0.05). Significant correlation between Sorcin and clinicopathological factors was analysed both in TA and SRCC (p<0.001) compared to ERK1/2 and Bcl2 expression. Sorcin expression was further associate with treatment response in non-responders (post-NACT) in both TA and SRCC (p<0.05).

[CONCLUSION] High ERK1/2, Sorcin, and low Bcl2 expression prevailed in SRCC cases. These expressions were upregulated post-NACT in both subtypes. SRCC patients had shorter OS, moreover expression of ERK1/2, Sorcin, and Bcl2 correlated with poor survival outcomes and major clinicopathological factors in SRCC cases.