Immunohistochemical analysis of a panel of cancer stem cell markers and potential therapeutic markers in pancreatic ductal adenocarcinoma

• Published in: Journal of cancer research and clinical oncology Vol. 149; no. 6; pp. 2279 - 2292
• Main Authors: Ali, S. M. Adnan, Adnan, Yumna, Ali, Saleema Mehboob, Ahmad, Zubair, Chawla, Tabish, Farooqui, Hasnain Ahmed
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2023; Springer Nature B.V
• Subjects: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Cancer Research; Carcinoma, Pancreatic Ductal - chemistry; Carcinoma, Pancreatic Ductal - diagnosis; Carcinoma, Pancreatic Ductal - therapy; CD44 antigen; Cyclin D1; Cyclooxygenase-2; Epidermal growth factor receptors; ErbB-2 protein; Female; Hematology; Humans; Immunochemistry; Immunohistochemistry; Internal Medicine; Male; Malignancy; Medicine; Medicine & Public Health; Middle Aged; Neoplastic Stem Cells - chemistry; Oncology; Original Article – Clinical Oncology; Pancreatic cancer; Pancreatic Neoplasms - chemistry; Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - therapy; Paraffin; Patients; PD-L1 protein; Precision medicine; Stem cells; Therapeutic applications; Therapeutic targets; Young Adult; Targeted therapies; Immunohistochemistry; Cancer stem cell markers; Pakistan; Pancreatic ductal adenocarcinoma
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-022-04315-4

Purpose Pancreatic Ductal Adenocarcinoma (PDAC) is the most common type of pancreatic malignancies. It is known for its aggressive nature and high mortality rate. This calls for an urgent need of new prognostic and therapeutic markers that can be targeted for personalized treatment of the patient. Methods Among 142 patients diagnosed with pancreatic cancers at Aga Khan University Hospital, a total of 62 patients were selected based on their confirmed diagnosis of PDAC. Immunohistochemistry was performed on Formalin-Fixed Paraffin-Embedded (FFPE) sections using selected antibodies (CD44, CD133, L1CAM, HER2, PD-L1, EGFR, COX2 and cyclin D1). All the slides were scored independently by two pathologists as per the set criteria. Results Expression of all cancer stem cell markers was found to be significantly associated with one or more potential therapeutic markers. CD44 expression was significantly associated with HER2 ( p =  0.032), COX2 ( p =  0.005) and EGFR expression ( p =  0.008). CD133 expression also showed significant association with HER2 ( p =  0.036), COX2 ( p =  0.004) and EGFR expression ( p =  0.018). L1CAM expression was found to be associated with expression of COX2 ( p =  0.017). None of the proteins markers showed association with overall survival of the patient. On the other hand, among the clinicopathological characteristics, histological differentiation ( p =  0.047), lymphovascular invasion ( p =  0.021) and perineural invasion ( p =  0.014) were found to be significantly associated with patient’s overall survival. Conclusion Internationally, this is the first report that assesses the selected panel of cancer stem cell markers and potential therapeutic targets in a single study and evaluates its combined expression. The study clearly demonstrates association between expression of cancer stem cell markers and therapeutic targets hence paves a way for precision medicine for pancreatic cancer patients.