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Epstein-Barr Virus-Associated Gastric Carcinoma and Specific Features of the Accompanying Immune Response.

Cho J, Kang MS, Kim KM - J Gastric Cancer (2016)

Bottom Line: In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra- or peritumoral immune cell infiltration.The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial.Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology & Translational Genomics, Samsung Medical Center, Seoul, Korea.

ABSTRACT
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is one of the four subtypes of gastric carcinoma (GC), as defined by the novel classification recently proposed by The Cancer Genome Atlas. EBVaGC has several clinicopathological features such as longer survival and higher frequency of lymphoepithelioma-like carcinoma (LELC) and carcinoma with Crohn's disease-like lymphoid reaction that distinguish it from EBV-negative GC. The intensity and pattern of host cellular immune response in GC have been found to significantly correlate with the prognosis of patients with GC, suggesting that immune reaction and tumor microenvironment have critical roles in the progression of GC, and in particular, EBVaGC. Here, we reviewed the cellular and molecular mechanisms underlying prominent immune reactions in patients with EBVaGC. In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra- or peritumoral immune cell infiltration. The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial. Overall, the underlying mechanisms and clinical significance of the host cellular immune response in patients with EBVaGC have not been thoroughly elucidated. Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC.

No MeSH data available.


Related in: MedlinePlus

Representative photographs of lymphoepithelioma-like carcinoma (A), carcinoma with Crohn's disease-like lymphoid reaction (B), and conventional adenocarcinoma (C) cells stained positive with Epstein Barr virus-encoded RNA in situ hybridization (magnification: A~C, ×40).
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Figure 1: Representative photographs of lymphoepithelioma-like carcinoma (A), carcinoma with Crohn's disease-like lymphoid reaction (B), and conventional adenocarcinoma (C) cells stained positive with Epstein Barr virus-encoded RNA in situ hybridization (magnification: A~C, ×40).

Mentions: In histological examinations, marked intra- or peritumoral immune cell infiltration is usually detected in EBVaGC samples. Previously, we divided EBVaGC into three histological subtypes according to the microscopic characterization of host cellular immune responses: LELC, CLR, and CA. Typical LELC was defined by (1) a well-defined tumor margin, (2) dense lymphocytic infiltration when the number of tumor-infiltrating lymphocytes (TIL) was greater than that of tumor cells, (3) indistinct cytoplasmic borders and a syncytial growth pattern with poorly formed glandular structures, and (4) absence of desmoplasia (Fig. 1A). CLR was characterized by (1) patchy lymphocytic infiltration with three or more lymphoid follicles with active germinal centers per tissue section at the advancing edge of the tumor, (2) lower number of lymphocytes compared to tumor cells, (3) frequent tubule or gland formation, (4) the presence or complete absence of minimal desmoplasia, and (5) increased intratumoral lymphocyte infiltration (Fig. 1B). Finally, cases showing infiltration of scattered lymphocytes with prominent desmoplasia in the absence of lymphoid follicles, or with only one or two lymphoid aggregates per tissue section, were classified as CA (Fig. 1C).19 The prognosis was affected by the intensity and pattern of the inflammatory response. Among them, LELC cases had the best prognosis, followed by patients with CLR, who, in turn, had better survival rates than those with CA.17192930


Epstein-Barr Virus-Associated Gastric Carcinoma and Specific Features of the Accompanying Immune Response.

Cho J, Kang MS, Kim KM - J Gastric Cancer (2016)

Representative photographs of lymphoepithelioma-like carcinoma (A), carcinoma with Crohn's disease-like lymphoid reaction (B), and conventional adenocarcinoma (C) cells stained positive with Epstein Barr virus-encoded RNA in situ hybridization (magnification: A~C, ×40).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834615&req=5

Figure 1: Representative photographs of lymphoepithelioma-like carcinoma (A), carcinoma with Crohn's disease-like lymphoid reaction (B), and conventional adenocarcinoma (C) cells stained positive with Epstein Barr virus-encoded RNA in situ hybridization (magnification: A~C, ×40).
Mentions: In histological examinations, marked intra- or peritumoral immune cell infiltration is usually detected in EBVaGC samples. Previously, we divided EBVaGC into three histological subtypes according to the microscopic characterization of host cellular immune responses: LELC, CLR, and CA. Typical LELC was defined by (1) a well-defined tumor margin, (2) dense lymphocytic infiltration when the number of tumor-infiltrating lymphocytes (TIL) was greater than that of tumor cells, (3) indistinct cytoplasmic borders and a syncytial growth pattern with poorly formed glandular structures, and (4) absence of desmoplasia (Fig. 1A). CLR was characterized by (1) patchy lymphocytic infiltration with three or more lymphoid follicles with active germinal centers per tissue section at the advancing edge of the tumor, (2) lower number of lymphocytes compared to tumor cells, (3) frequent tubule or gland formation, (4) the presence or complete absence of minimal desmoplasia, and (5) increased intratumoral lymphocyte infiltration (Fig. 1B). Finally, cases showing infiltration of scattered lymphocytes with prominent desmoplasia in the absence of lymphoid follicles, or with only one or two lymphoid aggregates per tissue section, were classified as CA (Fig. 1C).19 The prognosis was affected by the intensity and pattern of the inflammatory response. Among them, LELC cases had the best prognosis, followed by patients with CLR, who, in turn, had better survival rates than those with CA.17192930

Bottom Line: In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra- or peritumoral immune cell infiltration.The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial.Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology & Translational Genomics, Samsung Medical Center, Seoul, Korea.

ABSTRACT
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is one of the four subtypes of gastric carcinoma (GC), as defined by the novel classification recently proposed by The Cancer Genome Atlas. EBVaGC has several clinicopathological features such as longer survival and higher frequency of lymphoepithelioma-like carcinoma (LELC) and carcinoma with Crohn's disease-like lymphoid reaction that distinguish it from EBV-negative GC. The intensity and pattern of host cellular immune response in GC have been found to significantly correlate with the prognosis of patients with GC, suggesting that immune reaction and tumor microenvironment have critical roles in the progression of GC, and in particular, EBVaGC. Here, we reviewed the cellular and molecular mechanisms underlying prominent immune reactions in patients with EBVaGC. In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra- or peritumoral immune cell infiltration. The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial. Overall, the underlying mechanisms and clinical significance of the host cellular immune response in patients with EBVaGC have not been thoroughly elucidated. Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC.

No MeSH data available.


Related in: MedlinePlus