TY - JOUR
T1 - High extratumoral mast cell counts are associated with a higher risk of adverse prostate cancer outcomes
AU - Sullivan, Heidi Hempel
AU - Heaphy, Christopher M.
AU - Kulac, Ibrahim
AU - Cuka, Nathan
AU - Lu, Jiayun
AU - Barber, John R.
AU - de Marzo, Angelo M.
AU - Lotan, Tamara L.
AU - Joshu, Corinne E.
AU - Sfanos, Karen S.
N1 - Funding Information:
T.L. Lotan reports receiving a commercial research grant from Ventana/Roche. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
We would like to thank Christine Davis for assistance with image analysis. This work was supported by the Department of Defense Prostate Cancer Research Program, award numbers W81XWH-14-1-0364 (to H. Hempel Sullivan, A.M. De Marzo, and K.S. Sfanos), W81XWH-17-1-0286 (to T.L. Lotan, C.M. Heaphy, C.E. Joshu, and K.S. Sfanos), W81XWH-18-2-0013 (K.S. Sfanos), and W81XWH-18-2-0015 (A.M. De Marzo) Prostate Cancer Biorepository Network (PCBN).
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020
Y1 - 2020
N2 - Background: Given our previous findings that low intratumoral and high extratumoral mast cell numbers are associated with higher risk of biochemical recurrence after radical prostatectomy, we now assessed this relationship with race and the development of metastases. Methods: We stained for mast cell tryptase via IHC and fluorescent immunolabeling in 885 men across multiple tissue microarray sets designed to assess biomarkers in association with race and prostate cancer outcomes (median follow-up, 7.0 years). Results: Intratumoral and extratumoral mast cell counts were significantly lower in tissues from African-American compared with European-American men, but not within strata of cancer grade. There was no association between mast cell counts and ERG positivity, PTEN loss, or TP53 missense mutation. Higher minimum extratumoral mast cells were associated with an increased risk of biochemical recurrence [comparing highest with lowest tertiles: HR, 1.61; 95% confidence interval (CI), 1.12-2.29; P trend ¼ 0.01]; this pattern was similar among European-American and African-American men and by grade of disease. There was no significant association between minimum intratumoral mast cell count and biochemical recurrence, overall or within strata of race and grade. Finally, high minimum number of extratumoral mast cells was associated with prostate cancer metastases (comparing highest with lowest tertiles: HR, 2.12; 95% CI, 1.24-3.63; P trend ¼ 0.01). Conclusions: High extratumoral mast cell numbers are associated with biochemical recurrence and the development of metastases after radical prostatectomy. Impact: Higher numbers of benign tissue mast cells are associated with a higher risk of adverse outcomes after radical prostatectomy, including metastatic prostate cancer.
AB - Background: Given our previous findings that low intratumoral and high extratumoral mast cell numbers are associated with higher risk of biochemical recurrence after radical prostatectomy, we now assessed this relationship with race and the development of metastases. Methods: We stained for mast cell tryptase via IHC and fluorescent immunolabeling in 885 men across multiple tissue microarray sets designed to assess biomarkers in association with race and prostate cancer outcomes (median follow-up, 7.0 years). Results: Intratumoral and extratumoral mast cell counts were significantly lower in tissues from African-American compared with European-American men, but not within strata of cancer grade. There was no association between mast cell counts and ERG positivity, PTEN loss, or TP53 missense mutation. Higher minimum extratumoral mast cells were associated with an increased risk of biochemical recurrence [comparing highest with lowest tertiles: HR, 1.61; 95% confidence interval (CI), 1.12-2.29; P trend ¼ 0.01]; this pattern was similar among European-American and African-American men and by grade of disease. There was no significant association between minimum intratumoral mast cell count and biochemical recurrence, overall or within strata of race and grade. Finally, high minimum number of extratumoral mast cells was associated with prostate cancer metastases (comparing highest with lowest tertiles: HR, 2.12; 95% CI, 1.24-3.63; P trend ¼ 0.01). Conclusions: High extratumoral mast cell numbers are associated with biochemical recurrence and the development of metastases after radical prostatectomy. Impact: Higher numbers of benign tissue mast cells are associated with a higher risk of adverse outcomes after radical prostatectomy, including metastatic prostate cancer.
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U2 - 10.1158/1055-9965.EPI-19-0962
DO - 10.1158/1055-9965.EPI-19-0962
M3 - Article
C2 - 31932412
AN - SCOPUS:85081093715
SN - 1055-9965
VL - 29
SP - 668
EP - 675
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 3
ER -