Immunohistochemical Evaluation of the Expression of Specific Membrane Antigens in Patients with Pancreatic Ductal Adenocarcinoma

SIMPLE SUMMARY: Pancreatic ductal adenocarcinoma (PDAC) is an increasing cause of cancer-related death, due to its biologic aggressiveness and the lack of effective treatments. The cell membrane plays a significant role in carcinogenesis, expressing components that mediate the interaction with the peritumoral environment. The aims of our study were to evaluate the expression of six membrane components (CA 19-9, mucin 1 and 4 (MUC1, MUC4), mesothelin (MSLN), Glypican-1 (GPC-1), and Annexin A10 (ANXA10)) on 50 surgical samples of patients with PDAC and correlate it with the oncologic outcomes. The expression was assessed using the histo-score (H-score), a quantitative method based on immunostaining, on tumoral and peritumoral tissues. CA 19-9 and MUC1 showed an intense expression on tumor cells and a lower expression on pancreatic acini and ducts. Moreover, a high intensity of CA 19-9 correlated with a worse prognosis. MUC4, MSLN, GPC-1, and ANXA10 were selectively expressed by PDAC cells and may be potential biomarkers of the disease. ABSTRACT: (1) Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. The lack of validated disease biomarkers makes timely diagnosis challenging in most cases. Cell membrane and surface proteins play a crucial role in several routes of oncogenesis. The aim of this study was to evaluate the expression of six membrane antigens on PDAC (CA 19-9, mucin 1 and 4 (MUC1, MUC4), mesothelin (MSLN), Annexin A10 (ANXA10), Glypican-1 (GPC-1)) and their correlation with oncologic outcomes. (2) Methods: Immunohistochemical staining for CA 19.9, MUC1, MUC4, MSLN, ANXA10, and GPC-1 of surgical samples of 50 consecutive patients with PDAC was performed. Antigen expression for tumor, ductal, and acinar tissues was classified according to the histo-score (H-score) by two pathologists. (3) Results: Recurrence rate was 47% and 18 patients (36%) deceased (median follow-up 21.5 months). Immunostaining for CA 19-9 and MUC1 showed a significantly higher expression in the neoplastic tissue compared to non-tumor ductal and acinar tissues (p < 0.001). MUC4, MSLN, ANXA10, and GPC-1 were selectively expressed in the neoplastic tissue (p < 0.001). A CA 19-9 H-score value >270 was independently associated with a worse overall survival (p = 0.05) and disease-free survival (p = 0.05). (4) Conclusions: CA 19-9 and MUC1 are highly expressed in PDAC cells. The histological expression of CA 19-9 may predict prognosis. MUC4, MSLN, ANXA10, and GPC-1 are selectively expressed by neoplastic tissue and may represent a potential histological biomarker of disease.