| Objectives:Estrogen receptor(ER) and progestogen receptor (PR) play an important role in the occurrence, the development and the response to hormone of breast cancer. Endocrine therapy could be adopted in the cases of breast cancer with either ER or PR positive. C-erbB-2 protein coded by HER2 gene was regard as a prognosis factor and forecasting indicator of the treatment effects and the target for the treatment in breast cancer. Herceptin was widely used in the treatment of breast cancer, which has prolonged survival time and improved the life quality of breast cancer patients. When endocrine therapy and neoadjuvant chemotherapy emerged and were widely used, it seems to be more important to detect the ER and PR expression levels of preoperative breast cancer as a result of probable inconformity of ER and PR expression levels before and after chemotherapy. Fine needle aspiration cytology (FNAC) is a simple and practical technique for the preoperative diagnosis of breast cancer, and it is also used for the detection of ER, PR and HER2 expression levels. FNAC detecting effect is not always as good as we expected, especially it has disadvantages of detecting multiple antibodies simultaneously. Biological effects of androgen receptor (AR) were widely studied in prostate cancer, but they have been neglected in clinical and basic research field of breast cancer. There is no an affirmative conclusion about the clinical significance of AR expression in breast cancer and no satisfying answer about whether the AR expression is relevant to biology behavior of breast cancer, whether AR is correlated with ER, PR and c-erbB-2, and whether there is a difference of AR expression in different molecular subtypes of breast cancer.In the present study, it is aimed to improve traditional sliding method for immunocytochemistry and to enhance reliability of ER, PR and c-erbB-2 expression in preoperative specimen of breast cancer. The AR expression in breast cancer is further performed on tissue microarray, and their clinical significances are discussed.Methods:Fifty patients with breast cancer were examined by fine needle aspiration cytology (FNAC) after informed consent signed. ER, PR and c-erbB-2 were respectively detected on traditional cytology smears and liquid based cytology smears, and then compared with that on postoperative paraffin section. The product of Liqui-PREP test (LPT) was used in liquid-based cytology production, and immunohistochemistry SP method was used on tissue section.Two hundred cases of breast cancer specimen were made into two microarrays, with each one containing 100 spots of breast cancer. AR, ER, PR and c-erbB-2 expression levels of breast cancers were immunohistochemically detected by En Vision method, and the relationship between AR and clinicopathological characteristics, ER, PR, HER2 and molecular classification of breast cancer were analyzed.Semi-quantitative method was used in the judging immunostaining results of AR, ER, PR and c-erbB-2, and more than 10 percent of staining nucleus was regarded positive. The negative, weak positive, moderate positive and strong positive stain were corresponded with 0,1,2 and 3 score according to staing intensity. The percent of positive cells was observed in every slide and smear. The immunoreaction score is a product of the percent of the positive cells timing the staining intensity, ranging from 0 to 300 scores. More than 10 scores were regarde positive reaction. According to the breast cancer HER2 detection guide, the c-erbB-2 score 0 or 1+was regarded negative, and score 3+ was regarded positive, and score 2+ needs to be detected further by fluorescence in situ hybridization (FISH). HER2 gene amplification was regarded positive, when positive signals/control signals>2.2.The chi-squared test was used in comparing rates of ER and PR positive expression in liquid-based cytology smears, traditional smears and tissue sections. It was also used in comparing relationship between AR and clinical pathology indicators of breast cancer, ER, PR, HER2, and molecular classification of breast cancer. The difference of c-erbB-2 expression was tested in liquid-based cytology smears, traditional smears and tissue sections by Kruskal-Wallis test.Results:The tumor cells on the liquid based cytology smears were present in diffuse or scattered pattern with clear backgrounds, which were easily observed and judged. But the tumor cells on the traditional smears were in the massive and flaky pattern, and their backgrounds were full of the colors as a result of a large number of red blood cells and sphacelus that interfered observation and judgment. The positive expression rates of ER were 54%(27/50),50%(25/50) and 56%(28/50) in liquid based cytology smears, traditional cytology smears and paraffin sections, respectively; The positive expression rates of PR were 44%(22/50),38%(19/50) and 52%(26/50), and the positive expression rates of c-erbB-2 2+ or 3+ staining were 58%(29/50),54%(27/50) and 52(26/50), respectively. There was no statistics significance in the ER, PR, and c-erbB-2 expression difference of breast cancer in different sliding techniques (P>0.05). The positive rate of AR expression was 64.5%(129/200). There was no correlation between AR expression and clinicopathological characteristics such as ages, pausimenia, tumor location, lymph node metastasis, tumor histological types, TNM stages, infiltration and grades of carcinoma in situ, whereas the correlation was found between tumor volume, the grades of invasive duct carcinoma and AR expression. The positive rate of AR expression was differed in molecular classification of breast cancer, which was the highest in Luminal A subtype and Luminal A-HER2 subtype, moderate in Luminal B subtype and Luminal B-HER2 subtype, the lowest in HER2 subtype and triple negative subtype.Conclusion:1. The production quality of liquid-based cytology is superior to that of traditional cytology, attributing to abundantly intact cells and less background interference.2. The staining quality of ER, PR, and HER2 on liquid-based cytology smears is superior to that on traditional smears, contributing to judgment.3. AR expression of breast cancer was correlated with molecular classification, which was the highest in luminal-A subtype.4. AR expression level is associated with the tumor volume and histological grade of breast cancer. |
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