Abstract
BackgroundBetter methods to predict prognosis can play a supplementary role in administering individualized treatment for breast cancer patients. Altered expressions of PTHrP and TGF-β have been observed in various types of human cancers. The objective of the current study was to evaluate the association of PTHrP and TGF-β level with the clinicopathological features of the breast cancer patients.MethodsImmunohistochemistry was used to examine PTHrP and TGF-β protein expression in 497 cases of early breast cancer, and Kaplan-Meier method and COX’s Proportional Hazard Model were applied to the prognostic value of PTHrP and TGF-β expression.ResultsBoth over-expressed TGF-β and PTHrP were correlated with the tumor in larger size, higher proportion of axillary lymph node metastasis and later clinical stage. Additionally, the tumors with a high TGF-β level developed poor differentiation, and only TGF-β expression was associated with disease-free survival (DFS) of the breast cancer patients. Followed up for a median of 48 months, it was found that only the patients with negative TGF-β expression had longer DFS (P < 0.05, log-rank test). Nevertheless, those with higher PTHrP expression tended to show a higher rate of bone metastasis (67.6 % vs. 45.8 %, P = 0.019). In ER negative subgroup, those who developed PTHrP positive expression presented poor prognosis (P < 0.05, log-rank test). The patients with both positive TGF-β and PTHrP expression were significantly associated with the high risk of metastases. As indicated by Cox’s regression analysis, TGF-β expression and the high proportion of axillary lymph node metastasis served as significant independent predictors for breast cancer recurrence.ConclusionsTGF-β and PTHrP were confirmed to be involved in regulating the malignant progression in breast cancer, and PTHrP expression, to be associated with bone metastasis as a potential prognostic marker in ER negative breast cancer.
Highlights
Better methods to predict prognosis can play a supplementary role in administering individualized treatment for breast cancer patients
Correlation of TGF-β expression and clinicopathologic features All breast cancer cases were separated into two groups as TGF-β positive and TGF-β negative based on the TGF-β staining degree of the tumor sections
We found that positive expression of Parathyroid hormone-related protein (PTHrP)/TGF-β was linked to larger tumor size, higher proportion of axillary lymph node metastasis and later clinical stages
Summary
Better methods to predict prognosis can play a supplementary role in administering individualized treatment for breast cancer patients. The objective of the current study was to evaluate the association of PTHrP and TGF-β level with the clinicopathological features of the breast cancer patients. Parathyroid hormone-related protein (PTHrP), isolated from the tumor tissues of Malignancy-associated hypercalcemia (MAH) patients, was reported to be credited for its ability to mimic parathyroid hormone (PTH) [6, 7]. PTHrP expression was reported to be present in many tumor types even in the absence of hypercalcemia, and related with tumor progression such as colon cancer, non-small cell lung cancer, myeloma and prostatic cancer [13,14,15,16,17,18]. A recent study in PyMT-MMTV breast cancer mouse model reported that PTHrP expression level was correlated with breast cancer metastasis and tumor cell survival [21]
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