EPSTEIN-BARR TUMOR-ASSOCIATED INFECTION IS RESTRICTED TO MORE DISTAL ADENOCARCINOMA OF ESOPHAGOGASTRIC JUNCTION (AEGJ), WHILE PD-L1 IS HIGHLY IMMUNOEXPRESSED IN BOTH, ESOPHAGEAL SQUAMOUS CELL CARCINOMA (ESCC) AND AEGJ
Mateus B. Ribeiro*1, Sergio B. Marques2, Ibere C. Soares3, Marina A. Pereira3, Flavio R. Takeda3, Fauze Maluf-Filho3, Rubens A. Sallum3, Bruno Zilberstein3, Adriana V. Safatle-Ribeiro3, Ulysses Ribeiro3
1Universidade de Sao Paulo Faculdade de Medicina, São Paulo, Brazil; 2Universidade de Sao Paulo Hospital das Clinicas, Sao Paulo, São Paulo, Brazil; 3Universidade de Sao Paulo Instituto do Cancer do Estado de Sao Paulo, Sao Paulo, São Paulo, Brazil
Epstein-Barr virus (EBV)-associated tumors represent a distinct and well-recognized subtype of cancer in the head & neck region and in stomach. In contrast, EBV infection tumor role is controversial in esophageal squamous cell carcinoma (ESCC) and in adenocarcinoma of esophagogastric junction (AEGJ). EBV-associated gastric tumors comprised around 10% of the cases. Moreover, EBV infection is associated with higher rates of PD-L1 expression. PD-L1 expression is a positive predictive factor to immunotherapy response anti-PD-1, or anti-PD-L1 among different cancer types.
Aim: To evaluate the incidence of EBV-associated tumors in ESCC, and AEGJ; and to verify PD-L1 immunoexpression in the two main histological types of esophageal cancers.
Methods: Tissue Microarray (n = 5) was constructed using specimens from 62 ESCC and 71 AEGJ. EBV infection was detected by in situ hybridization, and PD-L1 by immunohistochemistry. Samples were considered positive when PD-L1 was expressed in more than 1% of tumor cells (TCs) or tumor infiltrating immune cells (TIICs). Clinical, histological and phenotypic features of EBV-associated tumors, and PDL-1 immunoexpression were assessed.
Results: All ESCC (100%) patients and 47 (66.2%) AEGJ were surgically treated with esophagectomy or total gastrectomy. Twenty AEGJ patients were classified as Siewert I, 24 as Siewert II, and 20 as Siewert III. Among 62 ESCC patients, none were positive for EBV. In AEGJ group, 7 (9.9%) of 71 were EBV positive. All of the positive cases were classified as Siewert III tumors (p=0.003). According to the Lauren classification, five cases were diffuse type, and two cases were mixed type. No association between EBV and clinicopathologic characteristics was found, including age, gender, pT, pN, or tumor grading. Univariate analysis evaluating clinicopathologic characteristics of AEGJ group showed an association of EBV infection with alcohol consumption (p=0.012). PD-L1 was positive in 32 (45.7%) AEGJ patients, and in 23 (37.1%) ESCC. In the 7 positive EBV tumors, 5 (71.4%) were PD-L1 positive. By univariate analysis, PD-L1 was not associated with any of the clinicopathological features in both histological subtypes.
Conclusions: 1. EBV infection is restricted to more distal AEGJ; 2. Positive EBV in AEGJ might help to differentiate esophageal from gastric origin tumor, with an impact on surgical treatment; 3. High frequency of PD-L1 positivity in both histological esophageal types may indicate higher probability of treatment responsiveness with anti-PD-L1 on esophageal neoplasia.
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