Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance

Shi, Min; Yu, Danghui; Chen, Ying; Zhao, Chenyan; Zhang, Jing; Liu, Qinghua; Chen, Ni; Zhu, Minghua

doi:10.3748/wjg.v18.i8.840

Cited by 142 publications

(130 citation statements)

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“…[31][32][33][34][35][36] In addition, the detection of pancreatic stellate cells immediately adjacent to pancreatic ductal adenocarcinoma epithelium correlates with adverse clinicopathological parameters. 6,7,37 Our group and others have shown that highly contractile pancreatic stellate cells can produce aligned collagen matrices in vitro, and the resultant topography can facilitate pancreatic ductal adenocarcinoma cancer cell migration. [38][39][40] Our immunohistochemical analysis suggests a positive correlation between alpha-smooth muscle actin expression and aligned collagen in the pancreatic ductal adenocarcinoma periductal stroma, which should be further validated on a larger patient cohort for potential mechanistic insight (Figure 4, Supplementary Figure S3).…”

Section: Discussionmentioning

confidence: 99%

“…4 In a number of different cancer types, stromal properties have demonstrated importance in disease identification, progression, and patient prognosis. [5][6][7][8][9][10][11][12] Given the pronounced desmoplastic reaction in pancreatic ductal adenocarcinoma, a large number of recent research efforts have focused on elucidating stroma-cancer interactions for both nuanced insight into disease progression and for potential diagnostic, prognostic, or therapeutic targets. 13 The dominant extracellular matrix component of most tumor stromas, including that of pancreatic ductal adenocarcinoma, is fibrillar collagen.…”

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confidence: 99%

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Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis

et al. 2015

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Pancreatic ductal adenocarcinoma continues to be one of the most difficult diseases to manage with one of the highest cancer mortality rates. This is due to several factors including nonspecific symptomatology and subsequent diagnosis at an advanced stage, aggressive metastatic behavior that is incompletely understood, and limited response to current therapeutic regimens. As in other cancers, there is great interest in studying the role of the tumor microenvironment in pancreatic ductal adenocarcinoma and whether components of this environment could serve as research and therapeutic targets. In particular, attention has turned toward the desmoplastic collagen-rich pancreatic ductal adenocarcinoma stroma for both biological and clinical insight. In this study, we used quantitative second harmonic generation microscopy to investigate stromal collagen organization and structure in human pancreatic ductal adenocarcinoma pathology tissues compared with non-neoplastic tissues. Collagen topology was characterized in whole-tissue microarray cores and at specific pathology-annotated epithelial-stroma interfaces representing 241 and 117 patients, respectively. We quantitatively demonstrate that a unique collagen topology exists in the periductal pancreatic ductal adenocarcinoma stroma. Specifically, collagen around malignant ducts shows increased alignment, length, and width compared with normal ducts and benign ducts in a chronic pancreatitis background. These findings indicate that second harmonic generation imaging can provide quantitative information about fibrosis that complements traditional histopathologic insights and can serve as a rich field for investigation into pathogenic and clinical implications of reorganized collagen as a pancreatic ductal adenocarcinoma disease marker. Pancreatic ductal adenocarcinoma is one of the most devastating human malignancies. It is currently the fourth leading cause of cancer death and projects to become the second leading cause by 2030. 1 The 5-year relative survival rate has remained in the single digits for decades. Pancreatic ductal adenocarcinoma is notoriously difficult to detect before an advanced, inoperable stage is reached due to nonspecific symptomatology and the retroperitoneal location of the pancreas, which makes palpation or routine biopsy of suspicious masses difficult. Recent advances in the sensitivity and specificity of preoperative imaging modalities such as computer tomography, magnetic resonance imaging, positron emission tomography, endoscopic ultrasonography, and endoscopic retrograde cholangiopancreatography have played an important role in enhancing pancreatic ductal adenocarcinoma diagnosis, detailing the relationship of lesions to nearby anatomical structures, and determining the course of management. 2 Despite these advances, only 10-15% of patients are diagnosed at a localized disease stage when surgical resection is possible as a potential curative therapy. However, postsurgical recurrence rates are high with 5-year survival rate of

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis

et al. 2015

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“…Moreover, this marker is upregulated when mesenchymal stem cells are recruited into growing tumors [21,22]. Tumor-associated stromal expression of FAP was found to be associated with more aggressive disease progression, and potential development of metastasis, recurrence, and death in colon and pancreatic cancers [23][24][25]. Previous studies in ovarian cancers treated with standard surgery followed by chemotherapy showed an association of FAP with advanced stage disease, lymph node metastasis, omental involvement, lymphovascular disease, and increased angiogenesis, but there is lack of data on the association of FAP with patient outcomes [26].…”

Section: Discussionmentioning

confidence: 99%

Clinical Implications of Marker Expression of Carcinoma-Associated Fibroblasts (CAFs) in Patients with Epithelial Ovarian Carcinoma After Treatment with Neoadjuvant Chemotherapy

Mhawech‐Fauceglia

Wang

Samrao

et al. 2013

Cancer Microenvironment

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Cancer-associated fibroblasts (CAFs) play an important role in tumor initiation and progression. The aim of this study is to explore the role of 2 CAF markers, fibroblast activated protein (FAP) and α-smooth muscle actin (αSMA), in patients with epithelial ovarian cancer (EOC) post-neoadjuvant chemotherapy. Sixty-six patients with the diagnosis of EOC treated with debulking surgery after neoadjuvant therapy were retrieved from the archives. Immunohistochemistry for FAP and αSMA antibodies were performed on paraffin-embedded tissue. αSMA was expressed by tumor-associated stroma in 95 % of cases and by tumor cells in 9 % of cases. No statistical power was found for αSMA and disease status. Our data indicate that FAP plays an important role in predicting tumor aggressiveness in patients with EOC post-neoadjuvant therapy, and its frequent expression in this malignancy implicates that FAP targeted therapy could be a very attractive strategy.

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“…Prominent presence of CAF FAP in the stroma of solid tumors is correlated to a poor prognosis in colon carcinoma and pancreatic adenocarcinoma [26,27] …”

Section: Fibroblast Activation Protein αmentioning

confidence: 99%

Functional subsets of mesenchymal cell types in the tumor microenvironment

Cortez

Roswall

Pietras

2014

Seminars in Cancer Biology

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In the field of tumor biology, increasing attention is now focused on the complex interactions between various constituent cell types within the tumor microenvironment as being functionally important for the etiology of the disease. The detailed description of tumor-promoting properties of cancer-associated fibroblasts, endothelial cells, pericytes, and immune cells, introduces novel potential drug targets for improved cancer treatments, as well as a rationale for exploring the tumor stroma as a previously unchartered source for prognostic or predictive biomarkers.However, recent work highlights the fact that cellular identity is perhaps too broadly defined and that subdivision of each cell type may reveal functionally distinct subsets of cells. Here, we will review our current understanding of the diversity of different subsets of mesenchymal cells, i.e., cancer-associated fibroblasts and pericytes, residing within the tumor parenchyma.

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Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance

Abstract: FAP is highly expressed in carcinoma cells and fibroblasts in PDAC tissues, and its expression is associated with desmoplasia and worse prognosis.

Cited by 142 publications

References 34 publications

Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis

Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis

Clinical Implications of Marker Expression of Carcinoma-Associated Fibroblasts (CAFs) in Patients with Epithelial Ovarian Carcinoma After Treatment with Neoadjuvant Chemotherapy

Functional subsets of mesenchymal cell types in the tumor microenvironment

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