Hormone receptor status in breast cancer – a comparison between surgical specimens and fine needle aspiration biopsies

The present study was performed to evaluate the immunocytochemical analysis (ICA) of oestrogen (ER) and progesterone receptor (PR) in fine needle aspiration (FNA) biopsies from primary breast cancers as compared with the established enzyme immunoassays (ER-EIA and PR-EIA) based on cytosol homogenates from the corresponding resected tumour specimens. A total of 967 primary breast cancers were assessed for ER and PR content by both methods. Correlations between EIA and ICA expressed as percentage of tumour cells with a positive staining were highly significant (P < 0.001) for ER and PR. Staining intensity yielded only limited additional information. The concordance between the two techniques was about 80%. Evaluation of biological parameters by FNA may be useful to decide the optimal treatment for breast cancer patients.     

ER/PR阳性和阴性乳腺癌的定量蛋白质组学和生物信息学比较研究

目的:建立雌/孕激素受体(ER/PR)阴性和阳性乳腺癌的蛋白质表达谱,寻找ER/PR阴性和阳性乳腺癌中差异表达蛋白,为乳腺癌患者提供新的预后预测指标和治疗新靶点。方法:应用蛋白质组学i TRAQ技术建立ER/PR阳性和阴性乳腺癌的蛋白质差异表达谱,鉴定两组乳腺癌的差异表达蛋白,对部分差异表达蛋白进行生物信息学分析,包括蛋白功能注释和分类GO分析和KEGG通路分析。结果:应用i TRAQ蛋白质组学技术对乳腺癌组织进行了蛋白组学分析,鉴定出ER/PR阳性和阴性组间有差异表达的蛋白4999种,以ER/PR阳性:ER/PR阴性≥3为上调标准,确定ER/PR阳性组上调蛋白101种。以ER/PR阳性:ER/PR阴性≤0.5为下调标准,ER/PR阳性组下调蛋白122种。GO分析结果显示ER/PR受体阴性和阳性乳腺癌的差异表达蛋白的分子功能、生物过程、细胞定位较为复杂,并且在上调蛋白和下调蛋白上存在分布差异。KEGG通路分析发现部分差异表达蛋白涉及201条信号通路。结论:ER/PR阳性和阴性乳腺癌间存在差异表达蛋白,这些蛋白涉及复杂的分子功能、生物过程和信号通路。     

Discrepancies between antibody (EIA) and saturation analysis of oestrogen receptor content in breast tumour samples

The use of different techniques for assay of oestrogen receptors (ER) in breast cancer raises the question of their relative effectiveness in measuring concentrations of functional receptors. Data were obtained on soluble receptors from supernatants from 58 primary breast tumour homogenates, using the ligand ([3H]oestradiol) binding assay with dextran-coated charcoal (DCC) separation, either at a single saturating ligand dose, or by Scatchard analysis, and by using the Abbott enzyme immunoassay (EIA) kit. As previous reports have shown, the two methods gave reasonably good correlation (r = 0.8), but EIA values were systematically higher than DCC (slope = 3.0). Similar values were obtained when the ER + ve/progesterone receptor (PR) + ve subgroup were examined separately (n = 34, r = 0.86, slope = 3.0). However the two sets of data were in much better agreement in the ER + ve/PR - ve subgroup (n = 10, r = 0.98, slope = 1.24). When analysed by isoelectric focusing on polyacrylamide gels (IEF), two major specific binding components were identified, at pI 6.1 and at pI 6.6. Both isoforms were present in 50/66 ER + ve PR + ve breast tumour samples, but only the pI 6.6 (4S) was present in most ER + ve/PR - ve samples (13/20). It appears that, compared with DCC, the EIA method gives much higher values for the 8S isoform, whereas the two methods detect the 4S isoform with similar sensitivity. In assays on the tumour cell lines, T47D and MCF-7, still greater discrepancies, at least 10-fold, were found between EIA and DCC data.     

Cytologic diagnosis of estrogen and progesterone receptors in breast imprints

OBJECTIVE: To investigate estrogen receptor (ER) and progesterone receptor (PR) levels in imprint specimens obtained at breast surgery and to compare their correlation with that of standard methods. STUDY DESIGN: Imprint specimens for cytology were obtained from 101 mass-forming lesions in 66 patients, and specimens were frozen in liquid nitrogen for later assay. The imprint specimens were immunocytochemically (ICC) stained by monoclonal antibody to ER or PR; diaminobenzidine-stained cell nuclei in clusters were regarded as positive. Tissue specimens were assayed by the standard method of dextran-coated charcoal assay (DCC) and enzyme immunoassay. RESULTS: Forty-five primary breast cancer lesions, 2 contralateral breast cancer, 49 dissected nodes and 5 benign breast lesions were collected. The correlation between DCC and ICC was 81% (82/101) for ER and 74% (66/101) for PR. That between EIA and ICC was 88% (88/99) for ER and 80% (79/100) for PR, higher than that between DCC and ICC for ER and PR. CONCLUSION: ICC assessment of ER or PR on imprint cytology is a promising clinical test with an acceptable correlation.     

Computer-assisted immunocytochemical determination of breast cancer steroid receptors on cytological smears of excised surgical specimens compared with frozen sections

BACKGROUND: Due to the widespread use of fine needle aspirate biopsy the practice of determining estrogen (ER) and progesterone (PR) receptors in breast carcinoma from cytological smears (CS) is becoming very common. The aim of this study was to determine concordance between ER and PR assessed by immunocytochemical assay (ICA) on CS and FS both evaluated by image analysis since we have found no data in literature on this. METHODS: 104 breast carcinoma cases were selected. For all cases ER and PR determination was performed on CS, obtained by light scraping of the freshly cut surface of the excised surgical tumors at the time of frozen section diagnosis, and FS using the same monoclonal antibodies. Computer-assisted image analysis was performed in all cases using CAS 200. Results were expressed as percent positive area of neoplastic nuclei compared with total nuclear area of the examined neoplastic cells. RESULTS: Good correlation was demonstrated between percent positive nuclear neoplastic area by ER-ICA on CS and FS (r = 0.759; P < 0.0001). Concordance of results was 90.19% (P < 0.001). Good correlation was also demonstrated between percent positive nuclear neoplastic area by PR-ICA in CS and FS (r = 0.889; P < 0. 0001). Concordance of results was 97.02% (P < 0.0001). CONCLUSIONS: Our data suggest that ICA on CS with automated image analysis is efficient in evaluating ER and PR content in human breast cancer, especially when CS is the only method pathologists have to evaluate receptor status e.g. in advanced breast cancer cases when neoadjuvant therapy is necessary before surgery or when surgery is impossible.     

Prognostic factors affecting disease-free survival rate following surgical resection of primary breast cancer.

In order to identify the prognostic factors that significantly influence the disease-free survival rate after surgical resection of primary breast cancers, we determined tumour and lymph node grades, and immunohistochemical staining for estrogen and progesterone receptors (ER and PR), c-erbB-2, p53, bcl-2, bax and PCNA in 76 patients. Univariate analysis showed that increased grade of tumour and lymph nodes, negative immunostaining for ER, positive immunostaining for c-erbB-2, and a high PCNA index (> or = 30%) negatively influenced the disease-free survival rate, but PR, p53, bcl-2 and bax had no predictive value. Although p53 was not an independent prognostic factor by itself, the combination of p53, bcl-2, and bax proved to correlate with the disease-free survival, with the best prognosis noted in tumours negative for p53 and positive for both bcl-2 and bax, intermediate prognosis in tumours negative for p53 and positive for either bcl-2 or bax and worst prognosis in tumors negative for p53 as well as bcl-2 and bax. Tumour grade correlated positively with PCNA index, while positive staining for ER correlated negatively with tumour grade as well as with PCNA index, although this was statistically insignificant. Immunostaining of breast cancers for bcl-2 correlated negatively with tumour grade and PCNA index. Immunostaining for c-erbB-2 correlated positively with PCNA but not with tumour grade. Immunostaining for p53 tended to correlate positively with PCNA, but not with tumour grade. Immunostaining for PR and bax did not correlate with tumour grade and PCNA index. These results suggest that in addition to tumour size and lymph node involvement, immunostaining for ER, c-erbB-2, and a high PCNA index are important prognostic factors in human breast cancer. Wild-type p53 with preserved bcl-2 and bax gene products is also a favorable prognostic factor indicating breast cancer at an early stage of cancer progression.     

Age-associated biomarker profiles of human breast cancer

To explore the hypothesis that aging not only increases breast cancer incidence but also alters breast cancer biology, we correlated patient age and diagnosis with tumor histology, stage and biomarkers independently determined from two different tumor archives: an American collection of approximately 800 paraffin-embedded and immunohistochemically analyzed primary breast cancers, and an European collection of approximately 3000 cryobanked primary breast cancers analyzed by ligand-binding and enzyme immunoassay (EIA). The prognostic biomarkers chosen for comparison represented surrogate measures of tumor: (i). proliferation, growth and genetic instability (mitotic and apoptotic indices, Ki-67/MIB-1-positivity, nuclear grade, p53-positivity), (ii). endocrine-dependence (estrogen receptor (ER), progesterone receptors (PR), pS2, Bcl2), (iii). growth factor receptor-dependence (ErbB2, EGFR/ErbB1), and (iv). angiogenic, invasive and proteolytic potential (uPA, PAI-1, Cathepsin D, VEGF). No biomarker reflecting tumor angiogenic, invasive or proteolytic potential showed a significant correlation with patient age at diagnosis. In contrast, significant inverse correlations (|r|>0.1; P< or =0.05) were observed for all measures of tumor growth and genetic instability as well as growth factor receptor overexpression (ErbB2 or EGFR positivity). Only one marker of endocrine-dependence, ER expression, showed a significant positive correlation with patient age at diagnosis. In summary, these findings support the hypothesis that breast cancer biology is significantly affected by patient age. In particular, breast tumors arising in older patients have slower growth rates, are more likely to be ER-positive, and are less likely to be p53-positive, EGFR-positive or ErbB2-positive.     

Expression of hormone receptors predicts survival and platinum sensitivity of high-grade serous ovarian cancer

High-grade serous ovarian cancer (HGSOC) has abundant expression of hormone receptors, including androgen receptor (AR), estrogen receptor α (ER), and progesterone receptor (PR). The effects of hormone receptors on prognosis of HGSOC were first evaluated in online databases. Their prognostic values were then explored and validated in our inhouse TJ-cohort (92 HGSOC patients) and in a validation cohort (33 HGSOC patients), wherein hormone receptors were detected immunohistochemically. High expression of hormone receptors denoted longer progression-free survival (PFS), overall survival (OS), and platinum-free interval (PFI). Platinum-sensitive patients had higher expression of hormone receptors than their counterparts. Correlation analysis revealed significant positive correlations between hormone receptors expression and survival. AR, ER, and PR had predictive and prognostic values, alone and in combination. By receiver operating characteristic curve (ROC) analysis, co-expression of AR, ER, and PR had an improved predictive performance with an area under the curve (AUC) value of 0.945. Expression of hormone receptors predicts survival and platinum sensitivity of HGSOC. AR, ER, and PR might be feasible prognostic biomarkers for HGSOC by immunohistochemical analysis.     

Prognostic evaluation of breast cancer in cytologic specimens

OBJECTIVE: To evaluate prognostic factors in breast cancer using cytologic samples and to determine the correlation between those factors and ploidy. STUDY DESIGN: Two hundred sixteen fine needle aspirates from patients with primary breast cancer were analyzed for expression of estrogen receptors (ERs), progesterone receptors (PRs), Ki-67 antigen, expression of p53 tumor suppressor gene and overexpression of c-erbB-2 using a standard immunochemical method. Not all subjects had all biomarker information because of the study design (c-erbB2 added later). The specimens were analyzed also for ploidy. We used the SAMBA 4000 image analysis system for quantification of the percent of cells stained positively by the different immunocytochemical stains andfor ploidy. RESULTS: A significant correlation wasfound between ER and PR and between Ki-67 and positive p53. Steroid receptor content was not significantly related to p53, Ki-67 or c-erbB2. No correlation was found between c-erbB2 and the other biomarkers. Ploidy had a significant correlation with all the biomarkers used. CONCLUSION: A reliable and rapid evaluation of markers for breast cancer can be achieved by measuring cells stained positively by immunocytochemical stains, as well as ploidy, by means of an image analysis system. ER, PR Ki-67, p53 and c-erbB2 had a significant correlation with ploidy and overall prognostic value in breast cancer.     

Alkaline phosphatases and steroid receptors in human breast cancer

Estrogen receptors (ER), progesterone receptors (PR) and alkaline phosphatases (AP) were measured in 150 tumors from patients who underwent mastectomy for primary breast cancer. The percentage of ER positive samples was inversely related to the AP activity ranging from 88.9% in low activity samples (less than 30 U/mg prot.) down to 30.6% in the high activity ones (greater than 400 U/mg prot.). When considering only ER positive samples, the ER content was inversely related to the AP activity. This could not be demonstrated for PR. Therefore, the authors suggest the hypothesis that in human breast cancer, the AP may play a role in the dephosphorylation of the ER molecule and in the consequent modulation of its binding capability.     

磁共振成像表观扩散系数与乳腺浸润性导管癌组织学分级及预后指标的相关性研究

目的:探讨磁共振成像(MRI)表观扩散系数(ADC)与乳腺浸润性导管癌组织学分级及其预后指标的相关性。方法:收集2016年5月至2017年5月于我院就诊的并经手术病理确诊为乳腺浸润性导管癌的患者112例作为研究对象,选取患者乳腺癌组织样本作为病例组,同时选取患者对侧正常乳腺组织样本作为对照组,所有患者均行常规MRI和磁共振扩散加权成像(DW-MRI)检查,分别测量两组样本的ADC值,比较不同乳腺浸润性导管癌组织学分级与正常乳腺组织的ADC值,分析乳腺浸润性导管癌组织的ADC值与肿瘤直径大小、淋巴结转移状态、有无远处转移及雌激素受体(ER)、孕激素受体(PR)和Ki-67表达的关系,并分析ADC值与组织学分级及预后指标的相关性。结果:乳腺浸润性导管癌病理分级I级的ADC值低于对照组,病理分级II级的ADC值低于病理分级I级及对照组,病理分级III级的ADC值低于病理分级II级、I级及对照组,差异均具有统计学意义(P0.05)。乳腺浸润性导管癌患者中,肿块直径2 cm、无淋巴结转移、ER阴性、PR阴性、Ki-67阴性患者的平均ADC值均高于肿块直径≥2 cm、有淋巴结转移、ER阳性、PR阳性、Ki-67阳性患者,差异均具有统计学意义(P0.05);而有无远处转移患者之间比较差异无统计学意义(P0.05)。经Spearman秩相关分析结果显示,乳腺浸润性导管癌患者的ADC值与病理组织学分级呈现负相关关系(rs=-0.716,P=0.000);与肿块直径大小、有无淋巴结转移及ER、PR、Ki-67的表达均呈负相关(rs=-0.316、-0.545、-0.667、-0.598、-0.443,P均0.05),与有无远处转移无相关性(rs=0.091,P=0.887)。结论:乳腺浸润性导管癌的ADC值与癌组织学分级和预后相关指标存在一定相关性,可作为一种临床诊断和判断预后的重要指标,具有重要临床价值。     

Expression of oestrogen receptor-beta in invasive breast tumours

Steroid hormone receptors are used routinely to predict endocrine responsiveness in patients with breast cancer. Two oestrogen receptors (ERs): ER alpha and ER beta have been identified. Although ER alpha and ER beta genes share a large degree of homology, it is generally thought that their distribution and function are substantially different in many tissues. Both of them may be expressed in normal and neoplastic tissues of the breast. While much is known about ER alpha, the role of ER beta is still undefined, especially at the protein level. Recent development of reliable antibodies to ER beta has provided opportunity to test immunohistochemical reactions detecting ER beta in archival breast tumours. The aim of our study was to learn more about the cellular mechanisms underlying the relationship of ER beta and progesterone receptor (PR) in breast cancer tissues, discriminating between hormone-dependent and hormone-independent tumours. ER alpha and PR content of tumour tissues of 154 patients with breast cancer were tested by in situ indirect immunohistochemical method parallel with ligand binding biochemical assay. ER beta was detected in 8 ER alpha-/PR+ breast carcinomas by immunohistochemical method too. Steroid hormone receptor content was analysed comparing to the histologic type and grading of the tumours. CONCLUSIONS: A considerable part of breast carcinomas belongs to the ER+/PR+ and ER-/PR- groups. About 1-2% of the tumours is expected to be ER alpha-/ER beta+/PR+ type. In such cases ER alpha negative reaction together with PR positivity can signal the necessity of the immunohistochemical detection of ER beta in routine histopathological practice, presenting the precise steroid hormone receptor status for the most effective endocrine therapy of the patients.     

老年乳腺癌患者的临床病理特点及其辅助治疗模式的研究

目的:探讨老年乳腺癌患者的临床病理特点及其辅助治疗模式,为老年乳腺癌患者的临床治疗提供参考。方法:选取2008年1月-2012年1月期间我院收治的50例老年乳腺癌患者作为研究对象,同时选取同期收治的50例中青年乳腺癌患者,比较两组患者的临床病理特征,并采用新辅助内分泌疗法治疗本组50例老年乳腺癌患者,治疗4个月后观察治疗效果。结果:老年乳腺癌患者的病灶5cm比例以及ER和PR阳性率均明显高于中青年患者,两组患者数据比较差异有统计学意义(P0.05);老年乳腺癌患者的淋巴结转移率、Ki67阳性率以及HER-2阳性率均低于中青年患者,两组患者数据比较差异均有统计学意义(P0.05);本组50例老年乳腺癌患者治疗总有疗效为82.0%,ER、PR均为阳性患者的治疗有效率为90.0%,明显高于ER和PR非双阳性患者(76.9%,57.1%),数据比较差异均有统计学意义(P0.05);TNM I期患者的治疗有效率为93.8%,明显高于TNM II期(76.9%)或TNM III期患者(20.0%),数据比较差异均有统计学意义(P0.05)。患者在治疗期间均未出现严重不良反应。结论:老年乳腺癌患者的生物学行为较好,病灶大、淋巴转移率低以及ER和PR阳性率高;新辅助内分泌治疗老年乳腺癌患者,尤其对ER、PR均为阳性以及TNM分期低的患者临床效果安全有效,不良反应发生率低,值得临床推广应用。     

Lack of relationship between the expression of hsp27 heat shock estrogen receptor-associated protein and estrogen receptor or progesterone receptor status in male breast carcinoma

Estrogen, through estrogen receptors (ERs), may regulate the synthesis of progesterone receptors (PRs) and of a heat shock estrogen receptor-associated protein (hsp27). In female breast carcinoma (FBC) both proteins serve as surrogate indicators for the presence of functional ERs. In addition, the expression of these proteins was related to other prognostic indicators of value in female breast tumours. Endocrine disorders, hormone therapy and altered estrogen metabolism have been associated with the development of male breast cancer (MBC), suggesting that evaluation of the expression of ER, PR and hsp27 might improve our understanding of the biology of this tumour. ER and PR status and hsp27 expression were evaluated by immunohistochemistry in 16 primary MBC patients. The interrelationships between these parameters were established and compared with the clinicopathological data on the tumours. Ten (56%) MBC patients were ER-positive, 69% were PR-positive and all samples were hsp27-positive. Our series of MBC patients showed a positive correlation between ERs and PRs, however there was a lack of correlation between hsp27 and ERs or PRs. MBCs did not exhibit any correlation between the biomarkers studied and known prognostic indicators for females (e.g. Scarff-Bloom-Richardson (SBR) or modified SBR (MSBR) grade, T stage, lymph node status). This is the first published series reporting the incidence of hsp27 in MBC. The lack of association between the expression of ERs and hsp27 found in MBC differs from the results reported for FBC, moreover the expression of ERs, PRs or hsp27 did not correlate with the clinicopathological parameters that have prognostic value in females. Although the data were obtained from a relatively small sample population, our findings suggest that MBC and FBC are biologically different tumours with respect to the expression of the studied proteins.     

Caspase-7在不同分子亚型乳腺癌中的表达及临床病理意义

目的:探讨含半胱氨酸的天冬氨酸蛋白水解酶(cysteinyl aspartate specific proteinase,Caspase-7,CASP7)在不同分子亚型乳腺癌中的表达及临床病理意义。方法:应用免疫组织化学方法检测CASP7在254例乳腺癌组织中的表达,重点观察该蛋白在不同分子亚型乳腺癌组织中表达的差异及与临床病理指标间的相关性,Kaplan-Meier法分析该蛋白表达与乳腺癌患者预后之间的关系。结果:Caspase-7在ER+PR+HER2+、ER+PR+HER2-、ER-PR-HER2+、ER-PR-HER2-中阳性表达率分别为37.2%、60.3%、17.0%、40.0%,在ER+/PR+/HER2-型中表达最高,在ER-/PR-/HER2+型中表达低,四组总体表达差异具有统计学意义(P0.001)。与ER、PR表达(均为r=0.194,P=0.002)呈显著正相关,与HER2表达2(r=-0.224,P0.001)呈显著负相关。在ER-PR-HER2+型乳腺癌中,CASP7的表达与肿瘤大小呈负相关(P=0.028),且与术后纵膈转移和脑转移呈正相关(均为r=0.307,P=0.026)。CASP7的表达与乳腺癌患者生存无显著相关性。结论:CASP7在不同分子亚型乳腺癌中表达存在差异,并且可能作为乳腺癌分子分型和预后预测的候选标记物。     

Estrogen and progesterone receptor status in primary breast cancer--a study of 11,273 patients from the year 1990 to 2002

The aim of this study was to gain insight of the breast cancer hormone receptor status of our patients, its stratification according to age as well as its changes during the period of 13 years. 11,273 patients with primary breast cancer from several towns in Croatia were included in this study. Patients' tumour specimens were collected from 1990 to 2002 and were analysed on estrogen (ER) and progesterone (PR) receptors in the Laboratory of the Department of Medical Oncology, University Hospital Centre Zagreb. More than half of our breast cancer patients had ER positive tumours (54.3%). We observed ER + tumours increased with age continuously, with highest percentage in the age group of 70 to 79 years (68.1%). Similarly, proportion of PR + tumours was higher in the older age groups, being the highest between 40 and 49 years (55.9%). During 13 years of the study, the increase in frequency and proportion of ER + tumours was observed (from 52% in 1990 to 62% in 2002) and decrease of PR + tumours (56% to 53%). We confirm previous findings that the risk of hormone dependent breast cancer increases with aging. Risk of ER + breast cancer increased for 10% from 1990 to 2002 and PR + tumours decreased for 3.5% in the same period.     

Application of multiplex PCR with histopathologic features for detection of familial breast cancer in formalin-fixed,paraffin-embedded histological specimens

Breast cancer is the most common malignancy among females in the world. In Iran, age and family history are the major risk factors for the development of this disease. Mutations of BRCA1 and BRCA2 genes are associated with a greatly increased risk for familial breast cancer. The frequency of BRCA mutations was identified in familial breast cancers (FBCs) and nonfamilial breast cancers (NFBCs) by molecular genetics, and morphological and immunohistochemical methods. Thirty-four formalin-fixed, paraffin-embedded breast tissue tumors were analyzed from 16 patients with FBCs and 18 patients with NFBCs. Three 5382insC mutations were detected by multiplex PCR in 16 FBCs. The immunohistochemical method was used to detect estrogen receptors (ER), progesterona receptors (PR), and TP53. Comparison of ER, PR, and TP53 exhibited a high difference (P < 0.0001) in FBCs and NFBCs. Our results demonstrated that 5382insC mutation, ER, PR, TP53, mitotic activity, polymorphism, necrosis and tubules can serve as the major risk factors for FBC. The text was submitted by the authors in English.     

Correlation between sex hormone receptors in normal and cancerous target tissues

According to the classic model of regulation of sex hormone receptors biosynthesis in target tissues, oestrogen stimulates and progesterone inhibits biosynthesis in both receptors. One of the consequences of this model is a direct correlation between oestrogen (ER) and progesterone receptors (PR) in target tissues. Here we investigate a correlation between ER and PR in calf endometrium and breast cancer (BC) tissues of women. A direct correlation was found between receptors in the calf endometrium (r = +0.70; p < 0.01). There were three variants of BC tissues: without correlation, with positive correlation (r = +0.49; p < 0.01), and with non-linear negative correlation between ER and PR. The last variant of samples were detected exclusively in patients operated in spring and fall. The non-linear negative correlation between ER and PR in BC tissues in spring and fall may indicate disregulation of sex hormone receptors biosynthesis under the influence of external factors.     

乳腺癌免疫组化检测在乳腺癌患者诊治中的意义分析

目的：探讨免疫组化检测在乳腺癌患者诊治中的价值。方法：随机选取2011年1月-2013年1月的68例经过空心穿刺活捡并病理确诊的乳腺癌患者为研究对象,均采用免疫组化检测ER、PR、P53、Bcl-2,全部采用CEF化疗方案治疗3个月后手术治疗,再运用免疫组化SP法检测化疗前后乳腺癌组织中以上指标的阳性表达率情况。结果：ER、PR化疗前后比较无统计学意义（P〉0．05）;而P53、Bcl-2比较有明显的差异性（P〈0．05）;ER、PR的阴性和阳性和疗效情况无明显差异性,而P53、Bcl-2的阴性和阳性表达和化疗的效果有明显的差异性,P〈0．05,具有统计学意义。结论：免疫组化检测中ER、PR对乳腺癌化疗前后无明显差异性,而化疗可通过抑制P53的表达来抑制乳腺癌增值并通过升高Bcl-2表达来调整肿瘤细胞分化。     

Integration of estrogen and progesterone receptors with pathological and molecular prognostic factors in breast cancer patients

In this study we have examined biopsies from women with localized primary breast cancer to investigate the prognostic performance of estrogen receptors (ER) and progesterone receptors (PR) for estimating the metastatic probability of the patients, and to explore whether discrimination gets better by combining clinicopathological and other molecular parameters into a score. This prospective study involved 205 patients with a median follow-up of 5 y. Among the evaluated clinicopathological data were: patient's age; tumor size; axillary lymph node involvement; and tumor grade. The most representative tumor samples were derived to a single laboratory for immunohistochemical evaluation of the following molecular markers: ER, PR, proliferating cell nuclear antigen (PCNA), p53 protein product, erbB-2 (HER-2/neu) oncoprotein, and P170 glycoprotein (mdr1 gen product). Distant metastases (study endpoint) appeared in 19.5% (40/205) of the patients, most of these patients presented a mixture of poor, regular and good prognostic factors. Disease-free survival analysis procedures (Kaplan–Meier method) identified tumor size, axillary lymph node involvement, tumor grade, receptor status, PCNA, p53, erbB-2 and P170 as useful prognostic factors. Proportional hazard regression analysis (Cox) identified in order of importance erbB-2, tumor size, receptors status, tumor grade and PCNA as useful prognostic factors. To facilitate the evaluation of the prognostic factors, a practical and simple score system was derived. A high pathological score identified 65% of the patients that developed distant metastases, while a high molecular score was obtained in 57% of patients with metastatic disease. There was a significant improvement in the diagnosis of probability of being with distant metastases when the pathological score was combined with the molecular score, 82% of the patients with distant metastases showed an elevated combined score. Validation of this scoring system will need further larger studies (validation set as opposed to the training set used in the present study). Due to the complexity of events in cancer, the evaluation of a combination of prognostic factors should be of value to clinicians to make a more objective estimate of the prognosis of individual breast cancer patients.