| IntroductionThe mammalian Y-box binding protein-1(YB-1) , belonging to a family of multifunctional proteins conserved from prokaryote to eucaryon , is one of proteins involved in transcriptional and translational regulation of a wide range of genes by specific binding of Y-box sequence (5'-CTGATTGGCCAA-3') in their promoters and enhancers. A typical Y-box binding protein contains three structure domains: the N-terminal domain is rich in alanine and proline which have transcriptional activation; the C-terminal domain consists of alternating basic and aromatic regions which have high hydrophilicity; the center cold shock domain (CSD) is highly conserved within the family of Y-box binding proteins. The CSD is involved in specific and non-specific RNA binding, and in specific DNA binding, which binds strongly to inverted CCAAT box. YB-1 is a multifunctional protein may expressed and involved in fundamental processes such as transcription, translation, mRNA splicing, DNA repair, cell proliferation and regeneration.Several laboratories have demonstrated that YB-1 play an important role in malignant tumorigenesis, aggressiveness, metastasis, multidrug resistance, chemotherapy and prognosis. Clinical pathologic researchers claimed that the nuclear localization of YB-1 could be an important therapeutic target against not only multidrug resistance but also tumor growth. Some studies showed that the expression of YB-1 can be found in many human malignant tumors such as osteosarcoma, prostate cancer, breast cancer, lung cancer, colon carcinoma and ovarian cancer etc. Particularly in prostate cancer and breast cancer. The expression of YB-1 in breast cancer patients who were treated with chemotherapy in can act as a molecular marker in clinical chemo-treatment. And nuclear expression of YB-1 is often associated with poor prognosis in various human malignancies, including breast cancer. In recent studies, scientists determined that YB-1 facilitated malignant tumor proliferation by positively regulated epidermal growth factor receptor (EGFR). And to suppress the expression of YB-1 can obviously inhibit the tumor growth. Breast cancer is very common in human malignant tumor and is the number one in female cancers. The data from World Health Organization (WHO) showed that there were about 1.2 million women suffering from breast cancer around the world every year, and 500000 died from breast cancer. The diagnosis ages of breast cancer in China seems younger than that in developed nation such as USA and European countries.While in clinical work pathologist found the age of breast cancer patients younger than American and European breast cancer patients.However, there were short of epidemiologic study for this. Besides, there is no research has been found about the relationship between the expression of YB-1 and clinical characteristics and molecular subtypes in young breast cancer. ObjectiveIn order to analysis the diagnostic age of breast cancer and find the percentage of young breast cancer patients in west regions of China; To investigate the expression and significance of YB-1protein in human young breast cancer; To analyze the relativity between YB-1 and ER, PR, HER2 and cilinical characteristics in human young breast cancer; To analysis the expression of YB-1protein between molecular subtypes in young breast cancer patients.MethodsThe clinical records of the patients with breast cancer from 1975 to 2005(30 years) were gathered in Xijing Hospital. The diagnostic age of breast cancer was analyzed and compared with data from Surveillance Epidemiology End Results(SEER)of the USA.The expression of YB-1, ER, PR, HER-2, CD44, CK5/6 and EGFR in human young breast cancer were studied by immunohistochemistry (IHC);The relationship between YB-1expression and significance with clinical characteristics as histologic type, histopathologic grading, tumor size and lymph node status were analyzed; Four different molecular subtypes of breast cancer(Luminal-A, Luminal-B,HER-2 and Basal-like) were defined by IHC markers of estrogen receptor (ER), progesterone receptor (PR), HER2 and CK5/6. And the relationship between the expression of YB-1 and can the molecular subtypes of breast cancer was also analyzed.Results(1) The epidemiologic statistics showed that the average diagnostic age of breast cancer among 3074 cases of breast cancer patients in Xijing hospital from 1975-2005 was 48.65. The peak period was from 45 to 54, among which there were 1006 patients and occupied 32.73%. There were 297 patients who were younger than 35 years old, which occupied 9.67%. Compared with data in SEER, there was an obvious difference between Chinese and American among the breast cancer patients on both of the diagnostic age and the distribution of whole diagnostic age. (2)The expression of YB-1 protein in tissues of young breast cancer patients (<35 years): the positive rate of YB-1 were 92.2% (59/64), among which nucleus staining rate were 53.1% (34/64), cytoplasm staining rate were 39.1% (25/64). When the tumor size >2cm that YB-1 were mainly stained in nucleus (40.6%); on the contrary, when the tumor size≦2cm that YB-1 were mainly stained in cytoplasm (20.3%). There were significant correlation between YB-1 expression paterns and tumor size (P=0.036). In all cases of breast cancer the main histopathologic type is grade 3.Interestingly, in this group YB-1 stained mainly in nucleus(37.5%). There were significant different expression paterns of YB-1 in different histopathologic grade of breast cancer (P=0.000). Our study showed that there were higher metastasis rate of lymph node (84.4%) among these young breast cancer patients. (3) Among all 64 young breast cancer patients, the subtype of Luminal-B was the majority (46.9%) and the next were Luminal-A (25%). YB-1 primarily expressed in nucleus (32.8%) in the subtype of Luminal-B and cytoplasm expression was only 9.4%. In HER-2 and Basal-like subtypes YB-1 expressed at a same percentage (10.9%). There were different expression paterns of YB-1 in different molecular subtypes (P=0.009)..Conclusions(1)Compared with data in SEER both of the average diagnostic age and peak period of breast cancer in west regions of China were younger than that in the USA. The percentage of young breast cancer patients in west regions of China is much higher than that in USA.(2)The expression paterns of YB-1 in young breast cancer were related with the histopathologic characteristics such as tumor size, histopathologic grading and lymph node status.(3)There were different kinds of expression of YB-1 among different molecular subtypes in young breast cancer. YB-1 maybe can be used as a new molecular target in the prevention and therapy in young breast cancer.
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