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Undifferentiated Carcinoma with Osteoclast-like Giant Cells of the Pancreas: Molecular Genetic Analysis of 13 Cases.

ABSTRACT: Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas is a rare malignancy regarded as a subvariant of pancreatic ductal carcinoma (PDAC) characterized by variable prognosis. UCOGC shows a strikingly similar spectrum of oncogenic DNA mutations to PDAC. In the current work, we analyzed the landscape of somatic mutations in a set of 13 UCOGC cases via next-generation sequencing (NGS). We detected a spectrum of pathogenic or likely pathogenic mutations similar to those observed in PDAC following previously published results (10 KRAS, 9 TP53, 4 CDKN2A, and 1 SMAD4, CIC, GNAS, APC, ATM, NF1, FBXW7, ATR, and FGFR3). Our results support the theory that UCOGC is a variant of PDAC, despite its unique morphology; however, a UCOGC-specific genomic signature as well as predictive markers remain mainly unknown. Programmed death ligand 1 (PD-L1) status remains an important predictive marker based on previous studies.

SUBMITTER: Hrudka J

PROVIDER: S-EPMC10970188 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Undifferentiated Carcinoma with Osteoclast-like Giant Cells of the Pancreas: Molecular Genetic Analysis of 13 Cases.

Hrudka Jan J Kalinová Markéta M Ciprová Vanda V Moravcová Jana J Dvořák Radim R Matěj Radoslav R

International journal of molecular sciences 20240314 6

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas is a rare malignancy regarded as a subvariant of pancreatic ductal carcinoma (PDAC) characterized by variable prognosis. UCOGC shows a strikingly similar spectrum of oncogenic DNA mutations to PDAC. In the current work, we analyzed the landscape of somatic mutations in a set of 13 UCOGC cases via next-generation sequencing (NGS). We detected a spectrum of pathogenic or likely pathogenic mutations similar to those ...[more]

PMID: 38542259

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Project description:Background and objectiveUndifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is a rare variant of malignant pancreatic tumor. There is still no standardized treatment for this uncommon subtype, as surgical resection with lymphadenectomy is the only potentially curative treatment so far. In this paper, we describe the current knowledge of this very rare specific subtype of pancreatic cancer (PC) as a narrative review.MethodsFor this review, we did not specify the time range of studies referred to due to limited data availability. Our inclusion criteria comprised previous studies, which specifically focused on the rare UCOGC subtype of PC as a confirmed histopathology, either pure or present together with other subtypes. We disregarded the studies involving any other PC subtype but not UCOGC, including undifferentiated and anaplastic carcinomas without osteoclast-like giant cell components.Key content and findingsThe limited available data precludes a definitive assessment of the efficacy of both neoadjuvant and adjuvant chemotherapy in the treatment of UCOGC. Monoclonal antibody pembrolizumab has been proven to be effective in metastatic cases. Multiple cases demonstrate a better overall survival rate for patients with UCOGC only versus those having UCOGC as a component with a pancreatic ductal adenocarcinoma (PDAC) histopathological subtype. The same conclusion can be also drawn comparing the survival rate of patients having pure UCOGC versus UCOGC with associated PDAC. Programmed cell death ligand-1 expression has been shown to be an important determinant, which shortens the survival period of patients diagnosed with UCOGC.ConclusionsThe rarity of UCOGC limits data for clinical courses and treatment plans. We need more data to better understand the relationship between pathogenic mutations, histological subtypes, and prognosis in PC, including UCOGC. Understanding UCOGC's molecular, clinical, radiological, and pathological characteristics can lead to earlier, more accurate diagnoses and better management.

Project description:BackgroundUndifferentiated carcinoma (UC) is a rare subtype of pancreatic cancer distinguished from UC with osteoclast-like giant cells (UC-OGC) in 2019, affecting interpretation of literature that does not distinguish these subtypes. We sought to identify translationally relevant differences between these 2 variants and compared with pancreatic ductal adenocarcinoma.MethodsWe characterized clinical and multiomic differences between UC (n = 32) and UC-OGC (n = 15) using DNA sequencing, RNA sequencing, and multiplex immunofluorescence and compared these findings with pancreatic ductal adenocarcinoma.ResultsCharacteristics at diagnosis were similar between UC and UC-OGC, though the latter was more resectable (P = .009). Across all stages, median overall survival was shorter for UC than for UC-OGC (0.4 years vs 10.8 years, respectively; P = .003). This shorter survival was retained after stratification by resection, albeit without statistical significance (1.8 years vs 11.9 years, respectively; P = .08). In a subset of patients with available tissue, the genomic landscape was similar among UC (n = 9), UC-OGC (n = 5), and pancreatic ductal adenocarcinoma (n = 159). Bulk RNA sequencing was deconvoluted and, along with multiplex immunofluorescence in UC (n = 13), UC-OGC (n = 5), and pancreatic ductal adenocarcinoma (n = 16), demonstrated statistically significantly increased antigen-presenting cells, including M2 macrophages and natural killer cells, and decreased cytotoxic and regulatory T cells in UC and UC-OGC vs pancreatic ductal adenocarcinoma. Findings were similar between UC and UC-OGC , except for decreased regulatory T cells in UC-OGC (P = .04).ConclusionsIn this series, UC was more aggressive than UC-OGC, with these variants having more antigen-presenting cells and fewer regulatory T cells than pancreatic ductal adenocarcinoma, suggesting potential for immune-modulating therapies in the treatment of these pancreatic cancer subtypes.

Dataset Information

Undifferentiated Carcinoma with Osteoclast-like Giant Cells of the Pancreas: Molecular Genetic Analysis of 13 Cases.

Publications

Undifferentiated Carcinoma with Osteoclast-like Giant Cells of the Pancreas: Molecular Genetic Analysis of 13 Cases.

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