Neutrophil-rich Gastric Carcinoma in the Integrated Cancer Registry of Eastern Sicily, Italy

Data di pubblicazione: 
ANTONIO IENI (1) ELEONORA IRATO (1), ANTONIO VENUTI (1), GIOVANNI BRANCA (1), ANTONINO PARISI (2), FRANCESCO FEDELE (1) and ROSARIO A. CARUSO (1) 1Dipartimenti di Patologia Umana e di Scienze dell’Ambiente, della Sicurezza, del Territorio, degli Alimenti e 2 della Salute (SASTAS), Università di Messina, Messina, Italy
ANTICANCER RESEARCH International Journal of Cancer Research and Treatment ISSN: 0250-7005


Background/Aim: Neutrophil-rich carcinoma is a variant of gastric carcinoma that has not been well-studied or characterized.

The purpose of the present study was to reveal the incidence and clinicopathological findings compared to ordinary gastric carcinoma. Patients and Methods: A population-based series of 430 gastric cancers, identified between 2003 and 2006 from the province of  Messina (insular Italy; population 62,450), was used. The number of tumor-infiltrating neutrophils was assessed in a semi-quantitative manner using the mean value of 20 non- overlapping high-power fields (magnification, 400; 0.08 mm2). Tumors with >10 neutrophils per 20 high-power fields were arbitrarily considered as neutrophil-rich gastric carcinomas. Moreover, MUC1 immunohistochemical expression was investigated to show possible correlation with neutrophil infiltration in gastric carcinomas. Results: Among 193 gastric cancers resected for curative purposes, 30 (15.54%) were represented by neutrophil-rich gastric carcinomas. These tumors occurred more frequently in patients aged more than 72 years (p<0.05), showing an inverse correlation with mucinous subtype according to the WHO classification (p<0.001) and expressed MUC1. However, intensity and distribution of MUC1 was heterogeneous, and independent of neutrophil infiltration within the tumor stroma.

Conclusion: Neutrophil-rich carcinoma seems to represent a distinctive morphological variant of gastric carcinoma, although  the true mechanism for the infiltration of neutrophils is still unclear.  Inflammatory cells and mediators are a key component of the tumor microenvironment and cancer-related inflammation has been proposed to  epresent the seventh hallmark of cancer (1). Neutrophils are believed to be rare in the tumor microenvironment (1). Recent data suggest that tumor-infiltrating neutrophils are characterized by a bi-polar pattern of activation similar to that observed in macrophages (M1/M2) and T-cell (Th1/Th2) polarization (2). Fridlender et al. showed the existence of N1 (antitumoral) and N2 (protumoral) tumor-infiltrating neutrophils (3). N1 neutrophils exert antitumor activities through tumor cytoxicity and enhancement of antitumoral immune memory, whereas N2 neutrophils favor tumor growth, invasion and metastasis, e.g. through proteolysis of xtracellular matrix components, promotion of angiogenesis and mediation of  immunosuppression (3-6). Therefore, tumor-infiltrating neutrophils may play an important role in tumor pathology, either by inhibiting and/or promoting tumor cell growth. 

There are a few studies regarding tumor neutrophilia and its association with gastric carcinomas (7-13). This present  work was undertaken to determine the incidence and clinicopathological features of neutrophil-rich gastric carcinoma in a well-defined population of Southern Italy. As MUC1 (episialin, epithelial membrane antigen, CA15-3 antigen) on cancer cells is involved in chemotaxis of the cells of the innate immune system (14-19), the expression pattern of MUC1 in neutrophil-rich gastric carcinomas was also analyzed and the results discussed relevant to current literature.