Prognostic Role of High-Grade Tumor Budding in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis with a Focus on Epithelial to Mesenchymal Transition

Lawlor, Rita T.; Veronese, Nicola; Nottegar, Alessia; Malleo, Giuseppe; Smıth, Lee; Demurtas, Jacopo; Cheng, Liang; Wood, Laura D.; Silvestris, Nicola; Salvia, Roberto; Scarpa, Aldo; Luchini, Claudio

doi:10.3390/cancers11010113

Cited by 50 publications

(53 citation statements)

References 44 publications

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“…Recent evidences suggest that tumor budding could represent one of the morphological hallmarks of EMT [20,21]. This hypothesis has been recently confirmed by a meta-analysis [22] that investigated the prognostic role of tumor budding and its relationship with the presence of EMT. Authors concluded that high tumor budding is a risk factor for all-cause mortality and they also confirmed that tumor budding is a morphological aspect intimately associated with EMT [22].…”

Section: Not Investigated In Clinical Studiesmentioning

confidence: 75%

Prognostic and predictive factors in pancreatic cancer

et al. 2020

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Pancreatic cancer is one of the leading causes of cancer death worldwide. Its high mortality rate has remained unchanged for years. Radiotherapy and surgery are considered standard treatments in early and locally advanced stages. Chemotherapy is the only option for metastatic patients. Two treatment regimens, i. e. the association of 5-fluorouracil-irinotecan-oxaliplatin (FOLFIRINOX) and the association of nabpaclitaxel with gemcitabine, have been shown to improve outcomes for metastatic pancreatic adenocarcinoma patients. However, there are not standardized predictive biomarkers able to identify patients who benefit most from treatments. CA19-9 is the most studied prognostic biomarker, its predictive role remains unclear. Other clinical, histological and molecular biomarkers are emerging in prognostic and predictive settings. The aim of this review is to provide an overview of prognostic and predictive markers used in clinical practice and to explore the most promising fields of research in terms of treatment selection and tailored therapy in pancreatic cancer.

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Section: Not Investigated In Clinical Studiesmentioning

confidence: 75%

Prognostic and predictive factors in pancreatic cancer

et al. 2020

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“…In PDAC, tumor-budding cells and adjacent stromal cells showed increased levels of the E-cadherin repressors ZEB1, ZEB2, and SNAIL1. Moreover, tumor-budding cells lose expression for membrane adhesion molecule E-cadherin and β-catenin, without detectable nuclear β-catenin, and favorize tumor budding detachment from the primary tumor [56]. High expression of ZEB1 in tumor-budding and stromal cells was correlated with high peritumoral invasion.…”

Section: Cd36 Promotes Tumor Metastasis In Pancreatic Cancermentioning

confidence: 94%

CD36 and CD97 in Pancreatic Cancer versus Other Malignancies

Tănase

Gheorghișan-Gălățeanu

Popescu

et al. 2020

IJMS

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Starting from the recent identification of CD36 and CD97 as a novel marker combination of fibroblast quiescence in lung during fibrosis, we aimed to survey the literature in search for facts about the separate (or concomitant) expression of clusters of differentiation CD36 and CD97 in either tumor- or pancreatic-cancer-associated cells. Here, we provide an account of the current knowledge on the diversity of the cellular functions of CD36 and CD97 and explore their potential (common) contributions to key cellular events in oncogenesis or metastasis development. Emphasis is placed on quiescence as an underexplored mechanism and/or potential target in therapy. Furthermore, we discuss intricate signaling mechanisms and networks involving CD36 and CD97 that may regulate different subpopulations of tumor-associated cells, such as cancer-associated fibroblasts, adipocyte-associated fibroblasts, tumor-associated macrophages, or neutrophils, during aggressive pancreatic cancer. The coexistence of quiescence and activated states in cancer-associated cell subtypes during pancreatic cancer should be better documented, in different histological forms. Remodeling of the local microenvironment may also change the balance between growth and dormant state. Taking advantage of the reported data in different other tissue types, we explore the possibility to induce quiescence (similar to that observed in normal cells), as a therapeutic option to delay the currently observed clinical outcome.

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“…EMT is a biological process in which the epithelial elements lose their polarity and cell-to-cell contacts, undergo cytoskeleton remodeling with morphological modifications, and acquire migratory capacity [11]. EMT has recently emerged as a crucial biological mechanism in undifferentiated carcinomas of other organs [12,13], and in PDAC has been strongly associated to poor prognosis [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Epithelial-mesenchymal transition in undifferentiated carcinoma of the pancreas with and without osteoclast-like giant cells

et al. 2020

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Undifferentiated carcinoma (UC) and undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) are peculiar variants of pancreatic ductal adenocarcinoma (PDAC), characterized by hypercellularity and absence of glandular patterns. The inflammatory microenvironment is peculiar in UCOGC, since it is dominated by macrophages and osteoclast-like giant cells. However, from a molecular point of view, both UC and UCOGC are very similar to conventional PDAC, sharing alterations of the most common genetic drivers. Clinically, UC usually show a worse prognosis, whereas UCOGC may show a better prognosis if it is not associated with a PDAC component. To highlight potential biological differences between these entities, we investigated the role of the epithelial to mesenchymal transition (EMT) in UC and UCOGC. Specifically, we analyzed the immunohistochemical expression of three well-known EMT markers, namely Twist1, Snai2, and E-cadherin, in 16 cases of UCOGC and 10 cases of UC. We found that EMT is more frequently activated in UC (10/10 cases) than in UCOGC (8/16 cases; p = 0.05). Furthermore, in UCOGC, EMT was activated with a higher frequency in cases with an associated PDAC component. Snai2 was the most frequently and strongly expressed marker in both tumor types (10/10 UC, 8/16 UCOGC), and its expression was higher in UC than in UCOGC (mean immunohistochemical score: 4.8 in UC vs. 2.1 in UCOGC, p < 0.01). Our results shed new light on the biology of UC and UCOGC: EMT appeared as a more important process in UC, and Snai2 emerged as a central EMT effector in this setting.

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Prognostic Role of High-Grade Tumor Budding in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis with a Focus on Epithelial to Mesenchymal Transition

Cited by 50 publications

References 44 publications

Prognostic and predictive factors in pancreatic cancer

Prognostic and predictive factors in pancreatic cancer

CD36 and CD97 in Pancreatic Cancer versus Other Malignancies

Epithelial-mesenchymal transition in undifferentiated carcinoma of the pancreas with and without osteoclast-like giant cells

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