scholarly journals Differential mast cell phenotypes in benign versus cancer tissues and prostate cancer oncologic outcomes

2020 ◽  
Author(s):  
Heidi Hempel Sullivan ◽  
Janielle P. Maynard ◽  
Christopher M. Heaphy ◽  
Jiayun Lu ◽  
Angelo M. De Marzo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mast Cell ◽  
Oncologic Outcomes ◽  
Cancer Tissues ◽  
Cell Phenotypes

scholarly journals Differential Mast Cell Phenotypes in Benign versus Cancer Tissues and Prostate Cancer Oncologic Outcomes

2020 ◽  
Author(s):  
Heidi Hempel Sullivan ◽  
Janielle P. Maynard ◽  
Christopher M. Heaphy ◽  
Jiayun Lu ◽  
Angelo M. De Marzo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mast Cell ◽  
Mast Cells ◽  
Biochemical Recurrence ◽  
Oncologic Outcomes ◽  
Cancer Tissue ◽  
Increased Risk ◽  
Minimum Number ◽  
One Year

AbstractWe previously reported that high numbers of mast cells in benign (extra-tumoral) regions of the prostate are associated with worse outcomes after radical prostatectomy including biochemical recurrence and the development of metastases. Herein, on a cohort of 384 men, we performed mast cell subtyping and report that higher minimum number of the tryptase-only (MCT) subset of extra-tumoral mast cells is associated with increased risk of biochemical recurrence (comparing highest to lowest tertiles: HR 2.20, 95% CI 1.32-3.65; P-trend 0.004), metastases (HR 3.60, 95% CI 1.77-7.36; P-trend 0.001), and death from prostate cancer (HR 2.96, 95% CI 1.23-7.08; P-trend 0.02). RNAsequencing of benign versus cancer tissue mast cells revealed differential expression of additional site-specific genes. We demonstrate that genes more highly expressed in tumor-infiltrating mast cells, such as CXCR4 and TFE3, represent an altered tumor microenvironment. C-kit variants were also differentially expressed in benign versus cancer tissue mast cells, with C-kit variant 1 (GNNK+) mast cells identified as more prevalent in extra-tumoral regions of the prostate. Finally, using an established mouse model, we found that mast cells do not infiltrate Hi-Myc tumors, providing a model to specifically examine the role of extra-tumoral mast cells in tumorigenesis. Hi-Myc mice crossed to mast cell knockout (Wsh) mice and aged to one year revealed a higher degree of pre-invasive lesions and invasive cancer in wildtype mice versus heterozygous and knockout mice. This suggests a dosage effect where higher numbers of extra-tumoral mast cells resulted in higher cancer invasion. Overall, our studies provide further evidence for a role of extra-tumoral mast cells in driving adverse prostate cancer outcomes.

scholarly journals MP40-13 PROGNOSTIC FACTORS AND ONCOLOGIC OUTCOMES AFTER ROBOT-ASSISTED RADICAL PROSTATECTOMY IN PT3B PROSTATE CANCER

2016 ◽  
Vol 195 (4S) ◽  
Author(s):  
Dae Keun Kim ◽  
Atalla Alatawi ◽  
Abulhasan Sheikh ◽  
Ibrahim Alabdulaali ◽  
Ali Abdel Raheem ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factors ◽  
Radical Prostatectomy ◽  
Oncologic Outcomes ◽  
Robot Assisted

Phenotypic and Quantitative Changes in Mast Cells after Syngeneic Unilateral Lung Transplantation in the Rat

1996 ◽  
Vol 91 (3) ◽  
pp. 319-327 ◽  
Author(s):  
Annick Buvry ◽  
Monique Garbarg ◽  
Violetta Dimitriadou ◽  
Agnès Rouleau ◽  
George F. J. Newlands ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Lung Transplantation ◽  
Left Lung ◽  
Muscle Layer ◽  
Rat Lung ◽  
Large Airways ◽  
Quantitative Changes ◽  
Cell Phenotypes ◽  
And Control

1. Lung transplantation causes a total interruption of the innervation and vascularization within the transplanted organ, followed by repair processes. This is frequently associated with bronchial hyper-responsiveness. A common feature of tissue repair is an increase in the number of mast cells. Three phenotypically distinct mast cell subsets, with respect to their protease content, have been identified in rat lung, and it is probable that mast cells of differing protease phenotype fulfil different functions. 2. We have compared the number, protease phenotype and distribution of mast cells in left lung from transplanted and control Lewis rats 1 month after syngeneic unilateral left lung transplantation, without interference of inflammation, graft rejection or of any treatment. Connective and mucosal-type mast cell phenotypes were characterized using antibodies directed against their specific rat mast cell proteases, RMCPI and RMCPII, respectively. 3. After transplantation, RMCPI and RMCPII tissue concentrations increased by 172% and 239%, respectively, compared with controls (13.1 ± 1.2 and 5.6±1.0 μg/g). 4. Localization of mast cell phenotypes was studied by immunohistochemistry after double immunostaining. The number of mast cells increased after transplantation: the increase in the number of RMCPI-immunoreactive mast cells (RMCPI+) was significant around bronchioles and arterioles, around large vessels and in the pleura. The number of RMCPII+ mast cells also significantly increased around bronchioles and arterioles, as well as in the smooth muscle layer of large airways. Some mast cells stained for the presence of both RMCPI and RMCPII, supporting the existence of co-expressing phenotype in rat lung. The number of mast cells of the RMCPI+ /H+ phenotype significantly increased around bronchioles and arterioles and in the pleura. Moreover, the distribution of the mast cell phenotypes was modified in the different areas after transplantation. 5. This indicates a local differentiation/maturation of mast cells after transplantation.

Stage at presentation and oncologic outcomes for agent orange exposed and non-exposed United States veterans diagnosed with prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 259-259
Author(s):  
Alexander Tward ◽  
Jonathan David Tward
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Cox Regression ◽  
Smoking Status ◽  
Initial Therapy ◽  
Agent Orange ◽  
Oncologic Outcomes ◽  
Free Survival ◽  
Risk Of Death ◽  
Increased Risk

259 Background: Exposure of Vietnam War Veterans to the defoliant Agent Orange (AO) has been linked to increased tumor stage of Veterans diagnosed with prostate cancer. However, information on the effect of exposure to treatment outcomes is lacking. The goal of this study was to evaluate oncologic outcomes in Veterans based on AO exposure history, accounting for known prognostic covariates not previously studied. Methods: United States military Veterans diagnosed with prostate adenocarcinoma born between the years 1930-1956 were identified from a large professionally curated institutional database. Evaluable patients had to have known AO exposure status, age, NCCN risk group, Charlson comorbidity score, smoking status, and whether initial therapy was surgical, radiation, or systemic. Risk of death, metastasis, and progression stratified by the type of initial therapy received was analyzed using Cox regression. Results: There were 70 AO exposed and 561 non-exposed Veterans identified, with a median follow-up of 10.0 years. AO exposure Veterans (AOeV) were significantly younger (64.0 versus 65.7 years, p=0.013) at diagnosis and presented at more advanced stages (e.g. Stage 4: 14.3% versus 2.5%) than non-exposed Veterans (non-AOeV). There was no difference for overall survival (HR=0.86, p=0.576, metastasis-free survival (HR=1.5, p=0.212), or progression-free survival (HR=0.67, p 0.060) between AOeV versus non-AOeV in analyses stratified by treatment received accounting for other prognostic covariates. Cigarette smoking was associated with a 2- 3-fold increased risk of death over those who quit or never smoked. Conclusions: Although AOeV do present at younger age and higher clinical stages than non-AOeV, the oncologic outcomes after accounting for treatments received and other prognostic covariates are similar. The implication is that AOeV are more likely to be recommended multimodality or systemic therapies at presentation.

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