ESOPHAGOGASTRIC JUNCTION ADENOCARCINOMA MAY BE BIOLOGICALLY CLASSIFIED BY IMMUNOEXPRESSION OF MOLECULAR MARKERS
Sergio B. Marques*2, Ibere C. Soares2, Mateus B. Ribeiro2, Marina A. Pereira2, Flavio R. Takeda2, Sergio Szachnowicz1, Rubens A. Sallum2, Fauze Maluf-Filho2, Ulysses Ribeiro2, Adriana V. Safatle-Ribeiro1,2
1Gastroenterology, University of Sao Paulo, Sao Paulo, SP, Brazil; 2Universidade de Sao Paulo Instituto do Cancer do Estado de Sao Paulo, Sao Paulo, São Paulo, Brazil
Esophagogastric junction adenocarcinomas (EGJA) have been surgically treated based on the epicentre of the tumor on pre-operative work up according to Siewert classification. Molecular classification may help to distinguish the tumor biologically and may add auxiliary information into treatment decision making. Immunohistochemistry is a cost-effective and easy-to-apply method that can be used instead of difficult and expensive molecular techniques. Aim: To classify the EGJA according to the immunoexpression of molecular markers and to compare these findings to Siewert classification. Methods: 71 patients with EJGA were enrolled from 2011 to 2018 for immunoexpression of markers by tissue microarray from specimens of biopsies and/or surgical tumor resection. Tumors were classified into four groups according to the immunoexpression: chromosomal instability (CIN): p53 and amplification of HER-2; Epstein-Barr virus (EBV): EBV in situhybridization and PD-L1; microsatellite instability (MSI): MLH-1 silencing; and genomically stable (GS): E-cadherin silencing. Siewert classification was defined according to endoscopy, computed tomography or surgical findings. Demographic data, clinical and histological features were evaluated. Results: Nineteen patients were classified as Siewert I, 27 as Siewert II and 25 as Siewert III. Male gender was associated to Siewert III (96%) compared to I (84%) and II (70%) (p=0.048). Clinical characteristics including age, body mass index, alcohol and cigarette consumption were similar in all three Siewert groups (p=NS). According to Lauren classification, the intestinal type was more frequently observed (74% in I, 85% in II and 56% in Siewert III). Positive p53 immunostaining was more significantly noticed in Siewert I (74%) and Siewert II (78%) than type III (16%) (p< 0.0001). HER-2 amplification was only detected in Siewert I (6/19; 31%) and II (5/27; 19%), while positive EBV was only seen in Siewert III patients (7/25; 28%). E-cadherin silencing was rarely and equally detected in all three Siewert groups (I= 16%; II= 15%; III= 13%). PD-L1 was positive in a high percentage of all three groups of patients (Siewert I= 42%; II= 54%; III= 42%) (p=0.59). MLH1 silencing was only observed in 3 patients, 2 in Siewert II and 1 in Siewert III group. Conclusions: 1. Immunohistochemical panel of markers helps to differentiate the EJGA and might influence on treatment strategy; 2. Siewert III tumors represent a distinct biological entity and should be treated differently; 3. High PD-L1 positivity in all sites of EJGA indicates that PD-L1 blockade may be utilized as a complementary therapy.
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