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

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.

High CD44 Immunoexpression Correlates with Poor Overall Survival: Assessing the Role of Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma Patients from the High-Risk Population of Pakistan.

Oral squamous cell carcinoma (OSCC) is a top-ranked cancer in the Pakistani population, and patient survival has remained unchanged at ∼50% for several decades. Recent advances have claimed that a subset of tumour cells, called cancer stem cells (CSCs), are responsible for tumour progression, treatment resistance, and metastasis, which leads to a poor prognosis. This study investigated the impact of CSC markers expression on overall survival (OS) and disease-free survival (DFS) of OSCC patients. Materials and Methods. Immunohistochemistry was used to evaluate CD44, CD133, L1CAM, and SOX2 expression in a well-characterized cohort of 100 Pakistani patients with primary treatment naïve OSCC. The immunoreactivity for each marker was correlated with patient clinicopathologic characteristics, oral cancer risk chewing habits, and survival. The minimum follow-up time for all patients was five years, and survival estimates were calculated using the Kaplan-Meier method and Cox proportional hazards model. Results. In this cohort of 100 patients, there were 57 males and 43 females. The median OS and DFS time durations observed were 64 and 52.5 months, respectively. Positive expression for CD44, CD133, L1CAM, and SOX2 was observed in 33%, 23%, 41%, and 63% of patients. High CD44 expression correlated with decreased OS (P=0.047) but did not influence DFS. However, CD133, L1CAM, and SOX2 had no effect on either OS or DFS. Tonsils, nodal involvement, and AJCC stage were independent predictors of worse OS and DFS both. Conclusion. Of the CSC markers investigated here, only CD44 was a predictor for poor OS. CD44 was also associated with advanced AJCC and T stages. Interestingly, CD133 was significantly lower in patients who habitually consumed oral cancer risk factors.

Genetic landscape of pancreatic adenocarcinoma patients: a pilot study from Pakistan.

BACKGROUND: Pancreatic adenocarcinoma is one of the most aggressive malignancies with extremely low survival rate. Studies have shown that the exploration of key genes can provide a basis for targeted treatment of these patients. The genomic architecture of the Pakistani pancreatic adenocarcinoma patients remains unexplored. Keeping the scenario in place, the current study aims to analyse 88 cancer related genes in Pakistani pancreatic adenocarcinoma patients in order to elucidate candidate gene(s) for targeted molecular therapy. METHODS AND RESULTS: A total 18 patients were included in the study initially and FFPE tumor samples were obtained. After confirmation of diagnosis and appropriate tumor content, DNA was extracted. Based on the quality and quantity of the extracted DNA, six pancreatic adenocarcinoma tumor samples were selected. Following to this, all the samples were subjected to targeted sequencing (Axen Cancer Panel 1). Variant detection was done and clinical significance of identified variants was assessed using ClinVar database. Targeted sequencing of tumor samples revealed a total of 29 alterations in the coding region of various genes. Among these five pathogenic variants were found in KRAS, BRCA1, TP53 and APC genes. CONCLUSION: This is the first study that explores genes involved in pancreatic adenocarcinoma from the Pakistani population. Results obtained from the pilot study can guide us about the key genetic players in the Pakistani pancreatic adenocarcinoma population. This can lead to our better understanding of the molecular targeted therapies for these patients and designing future researches on larger sample size.