HER Family Protein Expression in a Greek Population with Gastric Cancer. A Retrospective Hellenic Cooperative Oncology Group Study

• Published in: Anticancer research 2016-04, Vol.36 (4), p.1581-1590
• Main Authors: Makatsoris, Thomas, Tsamandas, Athanassios C, Strimpakos, Alexios, Alexopoulou, Zoi, Dionysopoulos, Dimitrios, Pervana, Stavroula, Konstantara, Athina, Papakostas, Pavlos, Samantas, Epaminontas, Rallis, Grigoris, Dimou, Anastasios, Pentheroudakis, George, Papaparaskeva, Kleo, Psyrri, Amanda, Kalogeras, Konstantine T, Syrigos, Kostas, Scopa, Chrisoula D, Fountzilas, George
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; ErbB Receptors - metabolism; Female; Greece - epidemiology; Humans; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms - epidemiology; Stomach Neoplasms - metabolism; Young Adult
• ISSN: 1791-7530

Gastric cancer is a relatively common malignancy. Recently, the presence of the human epidermal growth factor receptor 2 (HER2) was identified as a molecular target in a proportion of patients who benefited from the addition of appropriate anti-HER2 treatments. Our study explored the clinical and prognostic role of known HER family members, human epidermal growth factor receptor 1 (EGFR or HER1), HER2, HER3 and HER4. Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 249 gastric cancer patients were studied by immunohistochemistry for protein expression of EGFR, HER2, HER3 and HER4. Of the 249 evaluable patients, 32 did not have complete data of treatment details and/or follow-up and were excluded from the survival analyses. Of the 217 patients with complete treatment and follow-up data, 178 were operated and treated for early disease (group 1), while 39 for advanced disease (group 2). The frequency of positive EGFR, HER2, HER3 and HER4 protein expression in all patients was 17.5%, 11.8%, 14.8% and 32.9%, respectively. There were no differences in protein expression of any of the markers between the two groups. There were, however, statistically significant associations between HER4 and all other HER family members, as well as between HER2 and HER3 expression. Of note, EGFR-positive membranous protein expression was significantly associated with the presence of lymphovascular invasion (p=0.027) and HER3 and HER4 negative cytoplasmic protein expression with well/moderately-differentiated tumors (p=0.030 and p=0.014, respectively). None of the HER family members were of prognostic value for OS in univariate analysis. The present study confirmed the known protein expression frequencies of HER family members in gastric cancer in a Greek population. Several associations were observed among the HER family members and between clinicopathological characteristics and HER family members. Further research is needed on their exact prognostic role, as well as their therapeutic targeting.