Alexander Stojadinovic, Jeffrey A Hooke, Craig D Shriver, Aviram Nissan, Albert J Kovatich, Tzu-Cheg Kao, Sathibalan Ponniah, George E Peoples, Maria Moroni
Med Sci Monit 2007; 13(11): BR231-239
Available online: 2007-11-01
Background: Heat shock protein HYOU1, alternatively known as Orp150, plays an important role in hypoxia/ischemia and angiogenesis. Preliminary studies demonstrated increased HYOU1/Orp150 expression in prostate, bladder and invasive breast cancer. This study further evaluates HYOU1/Orp150 expression in different stages of breast cancer such as benign, pre-malignant and malignant lesions, and correlates it with clinical and pathological data.
Material/Methods: Sixty-six paraffin-embedded breast tissue sections were stained by immunohistochemistry using HYOU1/Orp150 antibody. Antibody staining was reviewed and scored 0 (lowest) to 3+ (highest). Clinico-pathological data was compared with HYOU1/Orp150 staining using ANOVA or Student’s t-Test as appropriate with significance determined by P<0.05.
Results: There was a small but significant increase (P<0.01) in HYOU1/Orp150 expression as the tumor transformed from benign (mean 1.52±0.12) to ductal carcinoma in situ (mean 2.05±0.14) and invasive carcinoma (mean 2.1±0.17). HYOU1/Orp150 was partially lost in the benign tissue adjacent to purely invasive cancer (0.88±0.22) and it was less (P=0.046) than what was found in benign only lesions (1.52±0.12) or in benign components adjacent to DCIS (1.47±0.16). Overexpression of HYOU1/Orp150 was associated with tumor lymph node involvement, presence of lymphovascular invasion, and absence of estrogen receptor expression (P<0.01). A trend was observed between HYOU1/Orp150 and nuclear p53 overexpression (P<0.04), but no correlation was detected with age, TNM stage, PR status, HER2/neu or Ki67.
Conclusions: HYOU1/Orp150 is overexpressed in some invasive breast cancers and its overexpression appears to be associated with indicators of poor prognosis. Its association with factors such as lymphovascular invasion and regional nodal involvement suggests a possible role for HYOU1/Orp150 in metastasis.
Keywords: Breast Diseases - metabolism, Proteins - metabolism, Prognosis, Neoplasm Staging, Neoplasm Invasiveness, Carcinoma, Intraductal, Noninfiltrating - metabolism, Breast Neoplasms - pathology, Breast Neoplasms - pathology, Proteins - metabolism, Prognosis, Neoplasm Staging, Neoplasm Invasiveness, Carcinoma, Intraductal, Noninfiltrating - metabolism, Breast Diseases - metabolism