Expression And Clinical Significance Of Bcl-2in Different Molecular Subtyping Breast Cancer

Purpose： Breast cancer is one of the most common malignant tumors in women.Worldwide, there are about1,300,000women suffering from breast cancer and50,000women dying from it. The main treatments for breast cancer include surgicalresection, chemotherapy, endorinotheraphy. Targeted therapy also plays a role for thetreatment of breast cancer and it will be more important in the future. Now, there aretwo kinds of molecular targeted drugs: inhibitor for ER and PR; inhibitor for HER2.Therefore, breast cancer has been divided into5different subtypes: luminal A,luminal B, HER2(+) subtype, basal-like subtype and normal breast-like subtypeaccording to immunohistochemistry expression of ER, PR and HER2. According tothe molecular subtyping, effective molecular targeted treatment was used for breastcancer patients to prolong their survival time and improve living quality. However,patients with the same molecular subtyping have different curative effect after themolecular targeted treatment. So, it is necessary to find a new molecular biomaker toperfect molecular subtyping of breast cancer. It has been reported that Bcl2proteinpositively expresses in lymphoid hematopoietic tissues, glioma, gastic cancer andkidney cancer. Bcl2plays an important role in the progression of breast cancer. It mayremedy the shortage of the current molecular subtyping. We investigated theexpression of Bcl2protein to explore its relationship with, the patients’ prognosisclinicpathological parameters and protein expressions of ER, PR and HER2and thendiscuss the supplement of Bcl2protein to the current molecular subtyping of breastcancer.Methods: A total of264breast cancer patients with clear pathological diagnosisincluding41patients with complete following-up were collected from the thirdpeople’s hospital of Dalian from2001to2005. The protein expression of Bcl2, ER,PR and HER2of the tissues were detected by immunohistochemistry. Furthermore,we divided the breast cancers into4different subtypes: luminal A, luminal B, HER2(+) subtype and basal-like subtype according to immunohistochemistry expression ofER, PR and HER2. The clinicopathological parameters included age, TNM, tumorsize, lymph node metastasis, histological grade, pathological types, invasion of vessels or nerves, and10-year-survival time.Results1. Clinicopathological parameters and Bcl-2: The expression of Bcl2is69.7%(184/264). The expression of Bcl2was not correlated with age, TNM stage, tumorsize, vessel invasion, nerves invasion and lymph node metastasis (P>0.05). Theexpression of Bcl2was significantly associated with histological grade (P=0.006).The rate of Bcl2expression in invasive lobular carcinoma was significantly higherthan that in other pathological types (p=0.002)2.Molecular subtyping and Bcl-2: The expression of Bcl2is68.7%in luminal A,81.6%in luminal B,68.7%in HER2(+) subtype and81.6%in basal-like subtype.The rates of Bcl2expression in luminal A and luminal B is significantly higher thanthat in the other2subtypes (P=0.000).3.Survival and Bcl-2: The expression of Bcl2in the following-up group was85.0%(35/41). The rate of Bcl2expression in survival group was higher than that in deathgroup (91.7%Vs76.5%). But no significant correlation was found (P=0.084).4.clinicopathological parameters and molecular subtyping: The264breast cancerswere classified into four groups:64in luminal A,144in luminal B,29in HER2(+)subtype and27in basal-like subtype. There were no significant correlations amongage, lymph node metestasis, vessel invasion nerves invasion and molecular subtyping.The tumor size was the smallest in luminal A while the largest in HER2(+) subtype(P=0.035). The grad I was the least in HER2(+) subtype and Grade III was the mostin basal-like subtype (p=0.000). Invasive ducted carcinoma was the least in luminal Band the most in HER2(+) subtype (p=0.023).5.ER, PR, HER2and Bcl-2: The expression of bcl2in ER positive group being81.5%is significantly higher than that in ER negative group being36.2%(P=0.000).The expression of Bcl2in PR positive group being82.5%is significantly higher thanthat in PR negative group being37.3%(P=0.000). The expression of Bcl2in HER2positive group being75.7%is significantly higher than that in HER2negative groupbeing58.2%(P=0.000). The expression of Bcl2in ER+PR+group being85.8%issignificantly higher than that in ER-PR-group being35.7%(P=0.000). Theexpression of Bcl2in ER+HER2+positive group being86.7%is significantly higherthan that in ER-HER2-group being35.5%(P=0.000). The expression of Bcl2in PR+HER2+positive group being86.8%is significantly higher than that in PR-HER2- group being36.1%(P=0.000).Conclusion1.Apoptosis inhibited the progression of breast cancer in Luminal A and Luminal Btypes. Apoptosis decreased which was induced by Bcl-2overexpression might bemore important for the progression of breast cancer in Luminal type.2.The breast cancer initiated by ER and PR might be significantly influenced byBcl-2.3.Bcl-2was mainly expressed in well differentiated breast cancer. Apoptosisdecreased played a major role in the progression of well differentiated breast cancer.4.The additional detection of Bcl-2might be helpful for the current molecularsubtyping and the clinical application of the molecular subtyping.