Relationship between tumor infiltrating lymphocytes and clinicopathological features in Peruvian gastric cancer.

Carlos Arturo Castaneda Altamirano Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru info_outline Carlos Arturo Castaneda Altamirano, Miluska Castillo Garcia, Luis A. Bernabe, Joselyn Sanchez, Matteo Fassan, Katherine Tello, Iván Chávez, Eloy Ruiz, Fernando Barreda, Daniel Valdivia, Yaqueline Bazan, Milagros Abad, Ebert Poquioma, Paola Catherine Montenegro, Luis Taxa

Authors Carlos Arturo Castaneda Altamirano Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru info_outline Carlos Arturo Castaneda Altamirano, Miluska Castillo Garcia, Luis A. Bernabe, Joselyn Sanchez, Matteo Fassan, Katherine Tello, Iván Chávez, Eloy Ruiz, Fernando Barreda, Daniel Valdivia, Yaqueline Bazan, Milagros Abad, Ebert Poquioma, Paola Catherine Montenegro, Luis Taxa Organizations Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru, Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy, Instituto Nacional De Enfermedades Neoplasicas, Lima, Peru, Instituto Regional de Enfermedades Neoplasicas del Norte, Trujillo, Peru Abstract Disclosures Research Funding Other Background: Role of tumor-infiltrating lymphocytes (TIL) over clinicopathological features including Mismatch Repair (MMR), HER2 status, Epstein Barr Virus (EBV) and Helicobacter pylori (HP) infection is not well understood in gastric cancer (GC). Methods: TIL level and HP infection was also evaluated in H&E from 503 Peruvian GC patients who underwent surgery. Density of CD3+ T cells, CD8+ cytotoxic T cells, CD163 M2 macrophages, as well as MMR and HER2 status were determined by immunohistochemistry. HP and EBV infection was also detected by qPCR in a 234 cases subset. Results: Median age was 62 years and 50.1% were female, most tumors were grade 3 (59.1%), intestinal subtype (44.8%) and stage III (59.8%). MMR loss was found in 29.4% and HER2+ in 4.7%. HP+ was detected by H&E in 55.7% and by qPCR in 63.7%. EBV+ by qPCR was found in 20.5% and co-infection along with HP in 9.4% (22/234). Stage (p < 0.001), intestinal histology (IH) (p = 0.019), grade (p = 0.006) and lymphovascular invasion (p < 0.001) were associated with longer survival. Median TIL was higher in invasive border (IB) and stromal (ST) than intratumoral (IT) compartment but there were significantly correlated (p < 0.001). High IT TIL was associated with absence of HP H&E (p = 0.009). High ST TIL was associated with older age (p < 0.001), IH (p < 0.001), grade 1 (p = 0.009), lower stage (p = 002), MMR loss (p = 0.019) and EBV+ (p = 0.001). Density of CD3 and CD8 were significantly correlated in IT and ST compartments (p < 0.001). High CD3 density in IT compartment was associated with grade 3 (p = 0.001) and HP- (p = 0.02), and in ST was associated with IH (p = 0.005), grade 1- 2 (p = 0.002) and MMR loss (p = 0.04). High IT CD8 was associated with HER2- (p = 0.016), HP- (p = 0.014) and EBV+ (p = 0.012). High ST CD8/CD3 ratio was associated with diffuse histology (p = 0.034), grade 3 (p = 0.013), more advanced stage (p = 0.022) and recurrence (p = 0.014). High ratio of IT CD8/CD3 was associated with MMR loss (p = 0.007). High ST TIL was associated with longer DFS (p = 0.007). Lower ratio of CD8/CD3 was associated with longer OS (p = 0.024) and DFS (p = 0.02). Conclusions: TIL levels and infiltrating immune subpopulations differs by clinicopathological features in GC including MMR loss, HER2 expression EBV and HP infection. ST CD8/CD3 was associated with recurrence and shorter DFS.