PD-L1 expression in pancreatic adenosquamous carcinoma: PD-L1 expression is limited to the squamous component

Tanigawa, Masahiko; Naito, Yoshiki; Akiba, Jun; Kawahara, Akihiko; Okabe, Yoshinobu; Ishida, Yusuke; Ishikawa, Hiroto; Hisaka, Toru; Fujita, Fumihiko; Yasunaga, Masafumi; Shigaki, Takahiro; Sudo, Tomoya; Mihara, Yutaro; Nakayama, Masamichi; Kondo, Reiichiro; Kusano, Hironori; Shimamatsu, Kazuhide; Okuda, K; Akagi, Yoshito; Yano, Hirohisa

doi:10.1016/j.prp.2018.10.006

Cited by 24 publications

(17 citation statements)

References 41 publications

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“…Another interesting paper demonstrates that pancreatic ASC displays higher PD-L1 levels, as compared to conventional PDAC. More in particular, the authors confirm that PD-L1 expression is detected only in the squamous component [88]. This evidence is particularly relevant for the possibility to stratify patients as PD-L1 negative or positive, hence as immune-checkpoint inhibitors non-responder or responder, respectively.…”

Section: Adenosquamous Carcinomamentioning

confidence: 52%

Morphologic and Molecular Landscape of Pancreatic Cancer Variants as the Basis of New Therapeutic Strategies for Precision Oncology

Bazzichetto

Luchini

Cognetti

et al. 2020

IJMS

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To date, pancreatic cancer is still one of the most lethal cancers in the world, mainly due to the lack of early diagnosis and personalized treatment strategies. In this context, the possibility and the opportunity of identifying genetic and molecular biomarkers are crucial to improve the feasibility of precision medicine. In 2019, the World Health Organization classified pancreatic ductal adenocarcinoma cancer (the most common pancreatic tumor type) into eight variants, according to specific histomorphological features. They are: colloid carcinoma, medullary carcinoma, adenosquamous carcinoma, undifferentiated carcinoma, including also rhabdoid carcinoma, undifferentiated carcinoma with osteoclast-like giant cells, hepatoid carcinoma, and signet-ring/poorly cohesive cells carcinoma. Interestingly, despite the very low incidence of these variants, innovative high throughput genomic/transcriptomic techniques allowed the investigation of both somatic and germline mutations in each specific variant, paving the way for their possible classification according also to specific alterations, along with the canonical mutations of pancreatic cancer (KRAS, TP53, CDKN2A, SMAD4). In this review, we aim to report the current evidence about genetic/molecular profiles of pancreatic cancer variants, highlighting their role in therapeutic and clinical impact.

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Section: Adenosquamous Carcinomamentioning

confidence: 52%

Morphologic and Molecular Landscape of Pancreatic Cancer Variants as the Basis of New Therapeutic Strategies for Precision Oncology

Bazzichetto

Luchini

Cognetti

et al. 2020

IJMS

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“…Specifically targeting activation of TP63ΔN (p40) network may prevent/revert transdifferentiation to basal-like type and open therapeutic avenues 29 , 33 . Selective expression of PD-L1 in the squamous component of ASCP in two studies 34 , 35 may also potentially suggest squamous differentiation as therapeutic target for immune checkpoint inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Morphological and p40 immunohistochemical analysis of squamous differentiation in endoscopic ultrasound guided fine needle biopsies of pancreatic ductal adenocarcinoma

Haugk

Horton

Oppong

et al. 2021

Sci Rep

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The basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis and upregulation in TP63ΔN (p40) network. Adenosquamous histology can be observed. This study assessed immunohistochemical p40 expression in fine needle biopsy (FNB) samples with PDAC and association with cytomorphological features of squamous differentiation and clinical data. 106 EUS FNBs with PDAC were assessed for eight cytomorphological features of squamous differentiation. P40 H-score (intensity 0–3 × percentage positive nuclei) was analysed for association with morphological features, patient age, gender, operability, chemotherapy and survival. P40 H-score in 14 paired FNBs and resections was compared. P40 h-score was 1–3 in 31%, 4–30 in 16% and > 30 in 13% of FNBs. It was significantly associated with intercellular bridges, elongated cell shape, sharp cell borders, angular nuclei with homogenous chromatin (p < 0.001) and dense cytoplasm (p = 0.002). Keratinisation was not seen. Inoperable patients (n = 81) had a shorter median survival for h-score > 30 (n = 9, 1.8 months) than for h-score ≤ 30 (n = 66, 6.7 months) not quite reaching statistical significance (p = 0.08). P40 was significantly associated with squamous morphology in FNBs with PDAC. P40 H-score > 30 showed a trend towards shorter survival in inoperable patients. Squamous differentiation may be a treatment target in PDAC.

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“…observed high expression of PD-L1 exclusively in the SCC component of pancreatic adenosquamous carcinoma samples. Moreover, mismatch repair gene (MMR) associated proteins were all positively expressed in both the squamous and adenocarcinoma components ( 10 ). In this case, expression levels of PD-L1 in pancreatic squamous cell carcinoma were 90%, but there was no loss of function of MMR proteins in the tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Squamous Cell Carcinoma of Pancreas With High PD-L1 Expression: A Rare Presentation

Yang

Ren

2021

Front. Oncol.

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Primary pancreatic squamous cell carcinoma is sporadic. The diagnosis is usually made following surgery or needle biopsy and requires a thorough workup to exclude metastatic squamous cell carcinoma. Squamous cell carcinoma of the pancreas often has a very poor prognosis. There is no treatment guideline for this type of cancer, and to date, no therapeutic regimen has been proven effective. Here, we report the effectiveness of immunotherapy in combination with chemotherapy against locally advanced squamous cell carcinoma of the pancreas with high programmed cell death ligand 1 (PD-L1) expression. Regional intra-arterial infusion chemotherapy consisting of nab-Paclitaxel followed by gemcitabine infused via gastroduodenal artery every three weeks for two cycles. This therapy resulted in the depletion of carcinoma, and the patient continues to lead a high-quality life with no symptoms for more than 16 months.

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PD-L1 expression in pancreatic adenosquamous carcinoma: PD-L1 expression is limited to the squamous component

Cited by 24 publications

References 41 publications

Morphologic and Molecular Landscape of Pancreatic Cancer Variants as the Basis of New Therapeutic Strategies for Precision Oncology

Morphologic and Molecular Landscape of Pancreatic Cancer Variants as the Basis of New Therapeutic Strategies for Precision Oncology

Morphological and p40 immunohistochemical analysis of squamous differentiation in endoscopic ultrasound guided fine needle biopsies of pancreatic ductal adenocarcinoma

Case Report: Squamous Cell Carcinoma of Pancreas With High PD-L1 Expression: A Rare Presentation

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