title: Co-expression of parathyroid hormone related protein and TGF-beta in breast cancer predicts poor survival outcome.
abstract: BACKGROUND
  Better 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.
  
  
  METHODS
  Immunohistochemistry 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.
  
  
  RESULTS
  Both 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.
  
  
  CONCLUSIONS
  TGF-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.
authors.affiliation: Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200090, China. xucheng@live.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200090, China. wangzhengyuan1980@gmail.com.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200090, China. rongincui@live.cn.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Cui
authors.affiliation: Department of Intensive Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. hehongyu@live.cn.
authors.forename: Hongyu
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200090, China. linxiaoyan077@163.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Thyroid and Breast Surgery, Changhai Hospital, Shanghai, 200433, China. sheng528yuan@gmail.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. zhang.hongwei@zs-hospital.sh.cn.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D044162:Parathyroid Hormone-Related Protein / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D016212:Transforming Growth Factor beta