Genomic Variations and Immune-related Features in Undifferentiated Carcinoma with Osteoclast-like Giant Cells of the Pancreas: a single center retrospective cohort study

Background: Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas (UCOGCP) was a rare malignancy. Literature on UCOGCP was limited, especially about mutation landscape and immune-related features.Methods: In the present study, the patients with UCOGCP admitted to West China Hospital of Sichuan University from 2010 and 2020 were retrospectively enrolled and followed until August 30, 2022. Whole exome sequencing (WES) and PD-L1 expression of tumor tissue from the 6 UCOGCP patients were performed to collect genomic variation and immune-related features of patients with UCOGCP.Results: We identified 11 (0.2%) patients with UCOGCP in the entire cohort of 5730 patients with pancreatic cancer (PC). 9 UCOGCPs were finally included in the analysis. In our cohorts, the median overall survival (mOS) was 39.8 months for UCOGCPs. Notably, compared with unresected patients (mOS, 9.1 months), the mOS of UCOGCPs who underwent surgical resection was dramatically improved (95.7 months). Molecular analysis in 6 samples revealed the most common gene mutations included KRAS (50%, 3/6) and TP53 (50%, 3/6) mutations. Two samples harbored a missense mutation at the same site of the LRP1 gene (33%). The median level of TMB was 0.75 mutations/Mb (range: 0 to 1.53 mutations/Mb). 100% of patients (6/6) were microsatellite stability (MSS). Three of 6 patients showed positive PD-L1 expression (tumor proportion score > 10%). Our study demonstrated a tendency that over-expression of PD-L1 was conversely related to survival time.Conclusions: This study demonstrated that the prognosis for resected UCOGCP was favorable in comparison to resected conventional pancreatic ductal adenocarcinoma (PDAC). Surgical resection still was the key to treat this disease. UCOGCP was similar to conventional PDAC at the molecular level, sharing somatic mutations in the most commonly mutated genes of PDAC. In addition, the mutations in LRP1 gene might be the potential driver of UCOGCP and be associated with poor prognosis. UCOGCP was characterized by low TMB, largely in MSS status and higher PD-L1 positive expression rates and extend. The expression of PD-L1 in UCOGCP indicated poor prognosis but such patients might benefit from immunotherapy.