The clinicopathologic significance of Tks5 expression of peritoneal mesothelial cells in gastric cancer patients

Abstract

Background Gastric cancer (GC) patients frequently develop peritoneal metastasis. Recently, it has been reported that peritoneal mesothelial cells (PMCs) activated by GC cells acquire a migratory capacity and promote GC cell invasion. The invasiveness of PMCs reportedly depends on the activity of Tks5, an adaptor protein required for invadopodia formation. However, the relationship between clinicopathologic features and Tks5 expression in PMCs has been poorly documented. In this study, we evaluated the clinicopathologic significance of the Tks5 expression of PMCs in GC patients. Materials and methods A total of 110 GC patients who underwent gastrectomy were enrolled in this study. Tks5 expressions in PMCs from the greater omentum, lesser omentum and retroperitoneum were evaluated by immunohistochemistry. We analyzed the correlation between Tks5 expressions in PMCs and the patients’ clinicopathologic features. Results Tks5 expression was found in 71 (64.5%) of the 110 patients, while 39 (35.5%) were Tks5-negative. Tks5 positivity was significantly (p = 0.038) associated with a greater tumor depth (i.e., T3/4 compared with T1/T2). Peritoneal recurrence was found in 12 of 98 cases within 3 years of surgery. The 3-year peritoneal recurrence-free survival (PRFS) rate in Tks5-positive cases was significantly poorer than that in Tks5-negative cases (80.1% vs 97.4%, p = 0.024). Multivariate analysis revealed that Tks5 positivity and lymph node metastasis were independent factors for PRFS. Conclusion Tks5 is frequently expressed in PMCs in advanced-stage gastric cancer. Tks5 might be a useful predictor for peritoneal recurrence in GC patients.

Crosstalk of tumor stromal cells orchestrates invasion and spreading of gastric cancer

“…79 The 3-year peritoneal recurrence-free survival rate was significantly lower in patients with TKS5-positive than TKS5-negative PMCs, but was not affected by Tks5 expression in cancer cells, indicating that Tks5 expression in PMCs may be a useful predictive marker of peritoneal recurrence in gastric cancer patients. 79 In addition to their roles in peritoneal metastasis, MCs also promote cancer chemoresistance and stemness. Ovarian cancer cells were found to induce osteopontin expression and secretion by MCs through TGF-β signaling.…”

“…Immunohistochemistry has shown that TKS5 is expressed by around 65% of PMCs from the omentum and retroperitoneum of gastric cancer patients who underwent gastrectomy 79 . The 3‐year peritoneal recurrence‐free survival rate was significantly lower in patients with TKS5‐positive than TKS5‐negative PMCs, but was not affected by Tks5 expression in cancer cells, indicating that Tks5 expression in PMCs may be a useful predictive marker of peritoneal recurrence in gastric cancer patients 79 …”

Integration of Genomic Biology Into Therapeutic Strategies of Gastric Cancer Peritoneal Metastasis

“…Mesothelial cells have been demonstrated to progressively acquire features of CAFs. 62 CAFs driven through TGF-b signaling pathways sustain and stimulate tumor proliferation. RHBDF2 expressed by CAFs is induced by inflammatory cytokines present in the malignant ascites and secreted by tumor cells.…”