F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología
Abstract
The purpose of this study is to investigate the
expression of succinate dehydrogenase (SDH)A, SDHB,
and HIF-1α in phyllodes tumors and the association with
clinic-pathologic factors. Using tissue microarray
(TMA) for 206 phyllodes tumor cases, we performed
immunohistochemical stains for SDHA, SDHB, and
HIF-1α and analyzed their expression in regard to
clinicopathologic parameters of each case. The cases
were comprised of 156 benign, 34 borderline, and 16
malignant phyllodes tumors. The expression of stromal
SDHA and epithelial- and stromal- SDHB increased as
the tumor progressed from benign to malignant
(P<0.001). There were five stromal SDHA-negative
cases and 31 stromal SDHB-negative cases. SDHB
negativity was associated with a lower histologic grade
(P=0.054) and lower stromal atypia (P=0.048).
Univariate analysis revealed that a shorter disease free
survival (DFS) was associated with stromal SDHB highpositivity (P=0.013) and a shorter overall survival (OS)
was associated with high-positivity of stromal SDHA
and SDHB (P<0.001 and P<0.001, respectively). The
multivariate Cox analysis with the variables stromal
cellularity, stromal atypia, stromal mitosis, stromal
overgrowth, tumor margin, stromal SDHA expression,
and stromal SDHB expression revealed that stromal
overgrowth was associated with a shorter DFS (hazard
ratio: 24.78, 95% CI: 3.126-196.5, P=0.002) and a
shorter OS (hazard ratio: 176.7, 95% CI: 8.466-3691,
P=0.001). In conclusion, Tumor grade is positively
correlated with SDHA and SDHB expression in the
tumor stroma in phyllodes tumors of the breast. This
result may be attributed to the increased metabolic
demand in high grade tumors