Does cellular senescence play an important role in the prognosis of sarcomatoid carcinoma of the pancreas?

Kimura, Toshihisa; Togawa, Tamotsu; Iida, Atsuo; Noriki, Sakon; Sato, Yasunori; Goi, Takanori

doi:10.1186/s12957-021-02177-7

Cited by 2 publications

(2 citation statements)

References 9 publications

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“…Collectively, the TGF-β/phospho-Smad/p53/p21 axis, associated with the concept of cellular senescence, seemed to be active only in the sarcomatoid cells of the long-term survivor. In agreement with this conclusion, the Ki-67 proliferation index of the long-term survivor was the lowest compared with the other two cases [27].…”

Section: Undifferentiated Sarcomatoid Carcinoma Of the Pancreas: What...supporting

confidence: 83%

“…In all the three cases, a positive staining for phospho-Smad2/3, Snail, and fibronectin was observed at the IHC level in sarcomatoid tumor cells. However, the expression of senescence markers, such as γ-H2AX, p53, and p21, was identified only in the sarcomatoid compartment of the long-term survivor, thus suggesting a potential correlation with prognosis [27]. TGF-β is a master-inducer of EMT [28,29].…”

Section: Undifferentiated Sarcomatoid Carcinoma Of the Pancreas: What...mentioning

confidence: 99%

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Undifferentiated Sarcomatoid Carcinoma of the Pancreas: From Histology and Molecular Pathology to Precision Oncology

Gkountakos

Simbolo

Bariani

et al. 2022

IJMS

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Undifferentiated sarcomatoid carcinoma of the pancreas (SCP) is a rare and aggressive subtype of pancreatic cancer. Histologically, SCP is a poorly differentiated tumor characterized by the lack of glandular differentiation and the presence of mesenchymal-like, spindle-shaped tumor cells. Due to its rarity, only sporadic cases have been reported, while its molecular characterization has not been sufficiently described. Surgical resection with curative intent is the gold-standard of SCP management, but this strategy is possible only in a small proportion of cases due to SCP early metastasization. Although SCP is generally associated with a poor prognosis, some clinical cases amenable to surgical resection and followed by adjuvant chemotherapy have demonstrated a remarkably long survival. Preliminary molecular insights on the SCP molecular landscape have demonstrated the recurrent presence of KRAS and TP53 mutations, highlighting genetic similarities with conventional pancreatic ductal adenocarcinoma (PDAC). Although the use of immunotherapy in PDAC remains an unmet challenge, recent insights indicated a potentially significant role of the PD-L1/Notch3 axis in SCP, opening new horizons for immunotherapy in this cancer subtype. In this review, we described the most important clinic-pathologic features of SCP, with a specific focus on their molecular landscape and the potential targets for precision oncology.

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Section: Undifferentiated Sarcomatoid Carcinoma Of the Pancreas: What...supporting

confidence: 83%

Section: Undifferentiated Sarcomatoid Carcinoma Of the Pancreas: What...mentioning

confidence: 99%

Undifferentiated Sarcomatoid Carcinoma of the Pancreas: From Histology and Molecular Pathology to Precision Oncology

Gkountakos

Simbolo

Bariani

et al. 2022

IJMS

View full text Add to dashboard Cite

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An Atypical Case of Pancreatic Cancer with Mesenchymal Differentiation in a Patient with Primary Lung Adenocarcinoma: Insights into Tumor Biology and Novel Therapeutic Pathways

Abbas,

Zahreddine,

Tawil

et al. 2024

Diagnostics

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Background: Pancreatic cancer is among the malignancies with the poorest prognosis, largely due to its aggressive nature and resistance to conventional therapies. Case Summary: This report describes the case of a 69-year-old male patient with stage IV primary lung adenocarcinoma presenting with high levels of programmed death-ligand 1 (PD-L1). Simultaneously, abdominal computed tomography (CT) showed a dilated pancreatic duct at the level of the pancreatic head and a hypodense lesion in the uncinate process involving the superior mesenteric artery. Fine-needle aspiration (FNA) of the pancreatic lesions was negative. After three cycles of chemoimmunotherapy, positron emission tomography–computed tomography (PET-CT) showed complete remission of the lung nodules, lymphadenopathy, and pleural thickening, as well as a decrease in the size of the pancreatic lesion. After another six months, a PET-CT scan showed a focal increased uptake in the pancreatic mass in the same location, indicating disease progression. A core biopsy of the pancreatic tumor showed atypical spindle cell morphology with positive staining for vimentin, characteristic of mesenchymal differentiation with no apparent epithelial features. Comprehensive molecular profiling through Caris Molecular Intelligence® revealed four genes with actionable mutations in the pancreatic tissue, including KRAS (p.G12D) and TP53 (p.R175H). These molecular findings suggested the diagnoses of sarcomatoid carcinoma and conventional pancreatic ductal adenocarcinoma with epithelial–mesenchymal transition. Primary mesenchymal tumors and neuroendocrine neoplasms were excluded because immunohistochemistry was negative for anaplastic lymphoma kinase (ALK), smooth muscle actin (SMA), desmin, CD34, signal transducer and activator of transcription 6 (STAT6), S100, HMB45, CD117, discovered on GIST-1 (DOG1), CD56, progesterone, and synaptophysin. However, despite multiple rounds of systemic chemotherapy, immunotherapy, and radiation, his pancreatic disease rapidly deteriorated and metastasized to the liver and bone. Conclusions: Despite multiple lines of treatment, the patient’s condition worsened and he succumbed to his pancreatic malignancy. This study highlights the clinical characteristics, diagnosis, and treatment of rare pancreatic cancer, emphasizing the importance of molecular testing and histopathological biomarkers in personalizing treatment. It also provides insights into promising therapeutic approaches for similar cases with an unusual presentation.

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Does cellular senescence play an important role in the prognosis of sarcomatoid carcinoma of the pancreas?

Cited by 2 publications

References 9 publications

Undifferentiated Sarcomatoid Carcinoma of the Pancreas: From Histology and Molecular Pathology to Precision Oncology

Undifferentiated Sarcomatoid Carcinoma of the Pancreas: From Histology and Molecular Pathology to Precision Oncology

An Atypical Case of Pancreatic Cancer with Mesenchymal Differentiation in a Patient with Primary Lung Adenocarcinoma: Insights into Tumor Biology and Novel Therapeutic Pathways

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