Combining lymphovascular invasion with reactive stromal grade predicts prostate cancer mortality

Sæter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M.; Axcrona, Karol; Axcrona, Ulrika

doi:10.1002/pros.23192

Cited by 15 publications

(12 citation statements)

References 26 publications

(35 reference statements)

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“…32 The authors also published on the relationship between reactive stroma grading and perineural invasion 33 and lymphovascular invasion. 34 Like our results, a group from Brazil 35 found that stromogenic carcinoma predicts biochemical recurrence on univariate but not multivariate analysis (266 patients). Unfortunately, a GL7 subset was not included in their analysis.…”

Section: Validation Of Stromogenic Carcinomasupporting

confidence: 77%

Moving Beyond Gleason Scoring

Miles¹,

Ittmann²,

Sayeeduddin³

et al. 2019

Archives of Pathology &Amp; Laboratory Medicine

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Context.— The combination of grading and staging is the basis of current standard of care for prediction for most cancers. D. F. Gleason created the current prostate cancer (PCa) grading system. This system has been modified several times. Molecular data have been added. Currently, all grading systems are cancer-cell based. Objective.— To review the literature available on host response measures as reactive stroma grading and stromogenic carcinoma, and their predictive ability for PCa biochemical recurrence and PCa-specific death. Data Sources.— Our own experience has shown that reactive stroma grading and the subsequently binarized system (stromogenic carcinoma) can independently predict biochemical recurrence and/or PCa-specific death, particularly in patients with a Gleason score of 6 or 7. Stromogenic carcinoma has been validated by 4 other independent groups in at least 3 continents. Conclusions.— Broders grading and Dukes staging have been combined to form the most powerful prognostic tools in standard of care. The time has come for us to incorporate measures of host response (stromogenic carcinoma) into the arsenal of elements we use to predict cancer survival, without abandoning what we know works. These data also suggest that our current definition of PCa might need some revision.

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Section: Validation Of Stromogenic Carcinomasupporting

confidence: 77%

Moving Beyond Gleason Scoring

Miles¹,

Ittmann²,

Sayeeduddin³

et al. 2019

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

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“…CAFs secrete high levels of a number of factors, including TGF‐ß, EGF, FGF, hepatocyte growth factor, insulin‐like growth factor‐1, interleukin‐6, and C‐X‐C motif chemokine ligand 12 (stromal cell‐derived factor‐1) that might reasonably be expected to act in a paracrine fashion and potentially promote tumorigenesis 42,44,45 . Seminal work on PCa stromal grading showed that reactive stroma grading is an independent predictive factor for PCa biochemical recurrence and PCa‐specific death 46–50 . In addition, functional and phenotypic heterogeneity is characteristic of CAFs, even of those extracted from the same tissues 51 …”

Section: Tissue Recombination Modelsmentioning

confidence: 99%

Current experimental human tissue‐derived models for prostate cancer research

2020

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Scientists engaged in prostate cancer research have been conducting experiments using two‐dimensional cultures of prostate cancer cell lines for decades. However, these experiments fail to reproduce and reflect the clinical course of individual patients with prostate cancer, or the molecular and genetic characteristics of prostate cancer, the basic requirement for most of the preclinical studies on prostate cancer. The use of human prostate cancer tissues in experiments has enabled the collection and verification of clinically relevant data, including chemical reactions, changes in proteins, and specific gene expression. Tissue recombination models have been employed for studying prostate development, the initiation and progression of prostate cancer, and the tumor microenvironment. Notably, the epithelial–stromal interaction, which might play a critical role in prostate cancer pathogenesis, can be reproduced in this model. Patient‐derived xenograft models have been developed as powerful avatars comprising patient‐derived prostate cancer tissues implanted in immunocompromised mice and could serve as a precision medicine approach for each prostate cancer patient. Spheroid and organoid assays, representative of modern three‐dimensional cultures, can replicate the conditions in human prostate tumors and the prostate organ itself as a miniature model. Although an intact immune system against the tumor is missing from the models aimed at investigating immuno‐oncological reagents in various malignancies, all these experimental models can help researchers in developing new drugs and selecting appropriate treatment strategies for prostate cancer patients.

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“…Seminal work on prostate cancer stromal grading showed that the two groups of tumors that are most aggressive are, 1) those with almost no stromal involvement, these seem to be independent of their microenvironment from early in their pathogenesis; and, 2) tumors that exhibit an abundant stromogenic response, where the stroma appears to be a major contributor to tumor growth and invasion (Ayala et al, 2003). Reactive stroma grading (RSG) is an independent predictive factor for PCa biochemical recurrence and PCa specific death (Ayala et al, 2011, McKenney et al, 2016, Saeter et al, 2015, 2016, Yanagisawa et al, 2007). …”

Section: Carcinoma-associated Fibroblastsmentioning

confidence: 99%

“…Reactive stromal grading (RSG) is an independent system based upon stromal phenotypes to divide tumors into one of four reactive stromal grades (0–3) (Yanagisawa et al, 2007, 2008). RSG provides a predictive factor for biochemical recurrence and disease-specific death in prostate cancer patients (Saeter et al, 2015, 2016) and can add significant predictive value to Gleason grading (McKenney et al, 2016). In contrast to clonal somatic gene studies, many differences have been found in gene expression between CAF and normal fibroblasts.…”

Section: Genetic and Genomic Analysis Of Cancer-associated Fibroblastsmentioning

confidence: 99%

Interaction of prostate carcinoma-associated fibroblasts with human epithelial cell lines in vivo

2017

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Stromal-epithelial interactions play a crucial and poorly understood role in carcinogenesis and tumor progression. Mesenchymal-epithelial interactions have a long history of research in relation to the development of organs. Models designed to study development are often also applicable to studies of benign and malignant disease. Tumor stroma is a complex mixture of cells that includes a fibroblastic component often referred to as cancer-associated fibroblasts (CAF), desmoplasia or “reactive” stroma. Here we discuss the history of, and approaches to, understanding these interactions with particular reference to prostate cancer and to in vivo modeling using human cells and tissues. A series of studies have revealed a complex mixture of signaling molecules acting both within the stromal tissue and between the stromal and epithelial tissues. We are starting to understand the interactions of some of these pathways, however the work is still ongoing. This area of research provide a basis for new medical approaches aimed at stabilizing early stage cancers rendering them chronic rather than acute problems. Such work is especially relevant to slow growing tumors found in older patients, a class that would include many prostate cancers.

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Combining lymphovascular invasion with reactive stromal grade predicts prostate cancer mortality

Abstract: Evaluating LVI together with reactive stromal grade on diagnostic biopsies could be used to identify patients at high risk of death from prostate cancer. Prostate 76:1088-1094, 2016. © 2016 Wiley Periodicals, Inc.

Cited by 15 publications

References 26 publications

Moving Beyond Gleason Scoring

Moving Beyond Gleason Scoring

Current experimental human tissue‐derived models for prostate cancer research

Interaction of prostate carcinoma-associated fibroblasts with human epithelial cell lines in vivo

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