Expression of the pS2 gene in normal breast tissue

Summary pS2 expression in normal breast tissue removed for cosmetic reasons was significantly lower than in uninvolved breast tissues from mastectomies for breast carcinomas. It is speculated that the presence of the carcinoma, or factors related to its development, could be the reason for this difference.     

Detection of estradiol-induced messenger RNA (pS2) in uninvolved breast tissue from mastectomies for breast cancer

Summary pS2 mRNA was estimated in uninvolved breast tissue and breast carcinoma from the same patients. pS2 mRNA was clearly detected in 14 of 59 uninvolved breast tissues and in 30 of 58 breast carcinomas. pS2 mRNA was found more frequently in uninvolved breast tissue of premenopausal women than in that of post-menopausal women.     

pS2蛋白在乳腺癌中的表达及意义

 目的　研究 pS2蛋白在乳腺癌中的表达及其临床意义。 方法　应用免疫组化S P法检测 10 0例原发性乳腺癌患者雌激素调节蛋白 pS2的表达。 结果　 10 0例乳腺癌患者中 ,pS2阳性表达 5 7例 ,占5 7% ,阴性表达 4 3例 ,占 4 3% ;pS2阳性表达与月经状况、ER、PR相关 ,与肿瘤大小、临床分期、淋巴结状况无关 ;pS2阳性表达者较阴性表达者五年生存率高 ,复发率低。单因素分析显示 ,pS2蛋白与乳腺癌患者的预后相关 ,pS2阳性表达者的预后优于 pS2阴性表达者 (P =0 .0 0 0 8,风险比 0 .370 )。多因素分析显示 ,pS2是影响患者术后生存的重要生物学指标。结论　pS2蛋白可能是预测乳腺癌患者预后的一个独立的预后因子。     

Immunohistochemical determination of pS2 in invasive breast carcinomas: a study on 942 cases

Summary To assess the practical prognostic value of pS2, we evaluated its expression by immunohistochemistry in paraffin-embedded tissue from 942 previously untreated invasive ductal carcinomas (IDC) resected in our center between 1980 and 1986. Positive staining of tumor cells was found in 684 cases (73%), but most of the tumors contained only a small amount of positive cells. There was a negative correlation between pS2 and tumor size (p = 0.01) and histological grade (p < 0.0001), and a positive correlation between pS2 and hormonal receptor status (p < 0.001). With respect to overall survival, pS2 positivity was associated with a better prognosis for the whole group and the node-positive sub-group. However, in terms of relapse and metastasis, pS2 was not significant. Furthermore, in multivariate analysis including tumor size, nodal status, histological grade, ER status, PR status, chemotherapy, hormonal treatment, and pS2, the latter appears to be of no prognostic value.     

乳腺癌中pS2、HSP27、Cath-D的表达及临床意义

 目的　探讨乳腺癌雌激素调节基因 pS2、HSP2 7、Cath D表达的临床意义。 方法　采用免疫组化S -P法检测 50例原发性乳腺浸润性导管癌中ER、pS2、HSP2 7、Cath -D的表达。 结果　pS2的表达与ER呈正相关性 (P <0 .0 1) ;与组织学分级呈负相关性 (P <0 .0 5)。HSP2 7表达与淋巴结转移、组织学分级及ER状态无相关性。有淋巴结转移的乳腺癌 ,间质Cath -D高表达率显著高于无淋巴结转移者 (P<0 .0 1)。结论　pS2表达与ER有关 ,pS2确能反映乳腺癌雌激素调节系统的完整性。间质Cath D表达与淋巴结转移有关 ,可作为判断乳腺癌预后的指标     

pS2 expression in primary breast carcinomas: Relationship to clinical and histological features and survival

Summary pS2 protein expression has been reported to have prognostic significance in human breast carcinomas and to correlate with estrogen receptor positivity, although these findings have not been confirmed by all investigators. pS2 positivity was compared to various clinical and histologic parameters in a retrospective study of 290 patients (median follow-up 7.2 years) and significantly correlated with tumor grade and estrogen receptor content (p=0.001 and p=0.0007, respectively). Significant associations between pS2 positivity and lymph node metastases, T stage, histologic tumor type, and patient age were not observed. Univariate and multivariate analyses (controlling for estrogen receptor content, T and N stage) of the patient population at large showed that pS2 positivity was not predictive of disease-free or overall survival. Univariate analysis of lymph node negative patients demonstrated that both pS2 and estrogen receptor positivity were significantly associated with a better outcome. Multivariate analysis of these patients, however, showed that only estrogen receptor data had independent prognostic significance. This study suggests that immunohistochemical analysis for pS2 protein expression will not contribute additional prognostic information if the estrogen receptor content is known.     

Differential distribution of ErbB-2 and pS2 proteins in ductal carcinomain situ of the breast

Summary We examined the expression of ErbB-2 and pS2 proteins in 59 ductal carcinomain situ (DCIS) of the breast, either pure DCIS or DCIS associated with invasive carcinoma, using immunohistochemical staining of paraffin-embedded sections. Positive staining for ErbB-2 and pS2 proteins was noted in 32% (19/59) and 46% (27/59) of DCIS, respectively. An inverse relationship between ErbB-2 and pS2 status in DCIS was observed (p < 0.01). From the viewpoint of histological subtype, the prevalence of ErbB-2 protein expression was significantly higher in the comedo subtype than the cribriform-micropapillary subtype. The prevalence of immunoreactivity for ErbB-2 in solid subtype was intermediate between those of the other two groups. In contrast, the prevalence of pS2 expression was significantly lower in the comedo subtype than in the cribriform-micropapillary subtype. Again, the prevalence of pS2 protein expression in the solid subtype was intermediate between those of the other two subtypes. Our results suggest that DCIS is biologically heterogeneous with regard to such marker substances. This has possible implications for management of these lesions.     

Multivariate analysis of oestrogen receptor alpha, pS2, metallothionein and CD24 expression in invasive breast cancers

Determination of oestrogen receptor alpha (ER) represents at present the most important predictive factor in breast cancers. Data of ours and of other authors suggest that promising predictive/prognostic factors may also include pS2, metallothionein (MT) and CD24. Present study aimed at determining prognostic and predictive value of immunohistochemical determination of ER, pS2, MT, and CD24 expression in sections originating from 104 patients with breast cancer. An univariate and multivariate analysis was performed. Both univariate and multivariate analyses demonstrated that cytoplasmic-membranous expression of CD24 (CD24c-m) represents a strong unfavourable prognostic factor in the entire group and in most of the subgroups of patients. In several subgroups of the patients also a prognostic value was demonstrated of elevated expression of pS2 and of membranous expression of CD24. Our studies demonstrated that all patients with good prognostic factors (higher ER and pS2 expressions, lower MT expression, CD24c-m negativity) survived total period of observation (103 months). The study documented that cytoplasmic-membranous expression of CD24 represented an extremely strong unfavourable prognostic factor in breast cancer. Examination of the entire panel of the studied proteins permitted to select a group of patients of an exceptionally good prognosis.     

乳腺癌pS2蛋白表达与内分泌治疗的关系研究

目的：探讨乳腺癌pS2蛋白的表达与内分泌治疗的关系。方法：应用免疫组化S－P法检测100例原发性乳腺癌组织中pS2蛋白的表达情况，并结合治疗及随访资料进行分析。结果100例原发性乳腺癌组织中，pS2蛋白阳性表达组与ER阳性表达组用TAM治疗后的生存率曲线显示，前者生存率高于后者（P＜0．05），结论：pS2蛋白表达的检测对乳腺癌患者的内分泌治疗有一定的指导意义。     

High Positive Rate of pS2 Expression in Forefront Intraductal Cancerous Area in Breast Cancer

Multiple sections of 40 consecutive cases with invasive ductal carcinoma of the breast, all of which had wide intraductal cancerous extension, were examined by immunohistochemicsl analysis for evaluation of hormone dependency in several areas of breast cancer tissues. In this study, we examined the expression of pS2 protein in the central invasive area (CIV), central intraductal cancerous area (CDC) and forefront intraductal cancerous area (FDC). pS2 staining was positive in 52.5% (21/40) of CIV and a significant correlation was found between pS2 expression in CIV and the estrogen receptor status (ER). pS2 staining was positive in 77.5% of CDC and 85.0% of FDC, respectively. A majority (68.4%) of the cases that were negative pS2 in CIV were positive for pS2 in FDC. Moreover, the cases with noncomedo intraductal carcinoma in premenopausal status showed a higher positivity of pS2 expression in FDC than the cases with comedo-carcinoma, though the number of cases of comedo-carcinoma was limited. These findings suggest that endocrine therapy may be useful after breast conserving treatment regardless of the ER status of the primary tumor.     

大肠癌组织中ER和PR及pS2表达的临床意义

目的：探讨ER、PR和pS2蛋白在大肠癌的表达以及在大肠癌发生、发展中的作用。方法：50例大肠癌术后标本作ER、PR和pS2免疫组化染色。结果：ER阳性表达率为28％（14／50），PR阳性表达率为68％（34／50），pS2蛋白阳性表达率为36％。pS2蛋白阳性表达与Duke’s分期有关，A、B期分别与D期比较差异有统计学意义，C期与D期间差异无统计学意义，P〉0．05；A、B、C期相互间差异无统计学意义，P〉0．05；pS2蛋白表达与ER、PR表达无相关性。结论：pS2蛋白在大肠癌组织中的表达与Duke’S分期有关，与肿瘤的侵袭有关。     

Loss of pS2 Protein Expression Is an Early Event of Intestinal-type Gastric Cancer

To investigate the prevalence of pS2 expression in gastric cancer with respect to tumor histopathology, intestinal metaplasia and Helicobacter pylori (H. pylori ) infection, pathologic specimens of 91 patients with gastric cancer were immunostained for pS2. Such immunoreactivity was correlated with the status of H. pylori infection, tumor staging, histology, subtyping, and associated intestinal metaplasia. Positive pS2 staining was seen throughout all non-neoplastic epithelia, and in all 9 patients with the complete type of intestinal metaplasia. In contrast, 21 of 45 incomplete type of intestinal metaplasia had negative pS2 staining ( P <0.001), and 54 out of 91 tumors (59.3%) showed loss of pS2 expression in the cancer tissues proper. There was no correlation of pS2 expression with age, gender, depth of invasion, duodenal involvement, lymph node metastasis, venous invasion or H. pylori infection. Negative pS2 staining was significantly higher in the intestinal (74.5%) and Borrmann type I, II, III (64.2%) tumors than the diffuse (43.2%, P <0.005) and Borrmann type IV (20%, P <0.05) tumors. Our results indicate that loss of pS2 expression may occur as an early event in the malignant transformation process of intestinal-type tumors.     

应用组织芯片技术研究抑癌候选基因NDRG2在甲状腺肿瘤组织中的表达及其意义

目的：应用组织芯片技术分析抑癌候选基因NDRG2在人类甲状腺癌组织、甲状腺正常组织及甲状腺良性病变组织中的表达情况。方法：采用小鼠抗NDRG2单克隆抗体的免疫组织化学ABC法,研究NDRG2在不同甲状腺组织的表达,并分析NDRG2在不同甲状腺组织中的表达差异。结果：免疫组化结果显示,甲状腺癌组织与甲状腺良性病变组织中DNRG2的表达相比较呈显著性差异（P〈0．05）,甲状腺癌组织与正常甲状腺组织中DNRG2的表达相比较呈显著性差异（P〈0．05）。甲状腺良性病变组织与正常甲状腺组织中DN—RG2的表达相比较呈显著性差异（P〈0．05）。结论：NDRG2在甲状腺癌组织中呈低表达,提示其可能对甲状腺癌的发生或发展有重要作用,这不仅为研究甲状腺癌的发病机制进一步提供了线索,而且对甲状腺癌的诊断和治疗具有重要意义。     

p53和Cat-D及p16和pS2的表达对乳腺癌预后的影响

探讨p53、Cat-D、p16和pS2表达与乳腺癌分期、淋巴结转移和预后的关系。方法:采用免疫组化SP法对160例乳腺癌组织进行p53、Cat-D、p16和pS2的检测。结果:随着肿瘤分期的提高,p53的阳性表达明显增加,pS2阳性表达明显降低,p16和Cat-D表达变化不显著。p53表达在有腋淋巴结转移者明显高于无腋淋巴结转移者(P<0.01),pS2、p16和Cat-D的表达则是无转移者高于有转移者(P<0.02～0.01)。p53表达在死亡组病例高于生存组,p16和Cat-D表达在生存组明显高于死亡组,而pS2的表达差异未达统计学意义(χ2=1.929)。结论:联合检测乳腺癌p53、p16、Cat-D基因表达对于判断预后和指导治疗可能具有实用价值。     

内吞作用相关基因FCHO2在乳腺癌中的表达及功能分析

目的：探讨内吞作用相关基因FCHO2在各亚型乳腺癌中的表达及其与乳腺癌患者的预后和免疫细胞浸润的相关性。方法：应用免疫组化法和bc-GenExMiner v5.0数据库数据分析FCHO2在各亚型乳腺癌组织中的表达,通过GEO和TIMER数据库数据分析FCHO2与各亚型乳腺癌患者预后和免疫细胞浸润的关系,利用STRING和GEPIA数据库数据分析与FCHO2的互作蛋白网络和其与互作蛋白的相关性,通过UALCAN和DAVID数据库数据对乳腺癌组织中FCHO2表达相关基因进行KEGG和GO分析。结果：免疫组化法结果显示,FCHO2在管腔型和HER2+乳腺癌组织中均呈高表达（均P<0.05）,且与HER2和Ki67表达有关联（P=0.03和P=0.007）。FCHO2高表达的管腔型乳腺癌患者总生存期（OS）和无复发生存期（RFS）均明显缩短（均P<0.05）。FCHO2蛋白与EPS15等多种蛋白表达相关且构成蛋白-蛋白互作网络。KEGG和GO分析显示,乳腺癌组织中FCHO2相关表达基因主要与昼夜节律、自噬等生物学过程有关,涉及叉头框蛋白O（FoxO）和TGF-β等信号通路。FCHO2表达与各亚型乳腺癌组织中的免疫细胞浸润相关（均P<0.05）。结论：FCHO2在管腔型、HER2+乳腺癌组织中呈高表达,且与管腔型乳腺癌患者预后及免疫细胞浸润相关,其可能成为乳腺癌治疗的潜在靶点。     

Tamoxifen aziridine binding to cytosolic proteins from human breast specimens is negatively associated with estrogen receptors, progesterone receptors, pS2, and cathepsin-D

[³H]Tamoxifen Aziridine ([³H]TAZ) is a derivative of the antiestrogen tamoxifen that covalently labels the Estrogen Receptor (ER), and perhaps other uncharacterized proteins. In a previous article we described that [³H]TAZ binds to a cytosolic protein from human uterine tissues that shares some, but not all, the ER properties. Here we have extended these studies to [³H]TAZ binding to cytosol proteins from human breast cancer specimens, and studied its quantitative association with other molecular markers and clinico-pathological variables. Cytosols were obtained in hypotonic buffer containing 20 mM molybdate and protease inhibitors, incubated with [³H]TAZ, and subjected to Sucrose Gradient Analysis (SGA). A [³H]TAZ labeled peak that consistently migrated with the 4S fractions was found in most of the assayed cytosols (range of 0 to 1278 fmol/mg p.). The 4S peak of [³H]TAZ was partially inhibited by both estrogens and antiestrogens. When [³H]E₂ was used instead of [³H]TAZ, only an 8S peak was detected. [³H]TAZ was covalently bound to a protein with an apparent MW of 65 kDa, as determined by SDS-PAGE and fluorography. The mean of [³H]TAZ binding was significantly higher in the subgroups of samples classified as ER-, PR-, pS2- or cathepsin D-, than in the respective positive subgroups (P < 0.01 in all the cases). [³H]TAZ binding was not associated with clinico-pathological variables, except that its mean was significantly larger in tumors larger than 5 cm than in smaller tumors. These results, and those previously reported, suggest that: 1) [³H]TAZ labels a cytosolic protein present in human breast cancers and uterine tissues that does not share all the ER properties, and 2) the [³H]TAZ binding by breast cancer cytosols is negatively associated with markers of estrogenic dependency, and its quantification may provide valuable information on antiestrogen responsiveness of a given tumor.     

凋亡相关基因bcl-xl在乳腺癌中的表达

为了探讨凋亡相关基因bcl-xl在乳腺癌中的表达及其临床意义,本文采用免疫络化SABC法和原位末端标记（TUNEL）法,分别对68例浸润性乳腺癌原发灶中bcl-xl蛋白及细胞调亡指数进行了检测。结果表现：bcl-xl蛋白在不同病理类型、年龄及临床分期中的阳性表达率无统计学差异（P＞0．05）;但在腋转移淋巴结＜4个组和≥4个组的阳性表达率分别为45％和71．4％（P＜005）;bcl-xl蛋白明性组和阳性组的平均凋亡指数分别为0．32％和0．18％（P＞0．05）。提示：bcl-xl蛋白与腋淋巴结转移有关,有可能作为乳腺癌预后判断的一个指标。     

bcl—2基因在乳腺癌中的表达及临床意义

目的研究bcl-2基因在乳腺癌癌灶、癌旁组织、转移淋巴结及正常组织中的表达,与肿瘤形成、发展的关系及临床意义.方法应用相对定量RT-PCR方法,检测bcl-2基因在16例乳腺癌癌灶、癌旁组织、转移淋巴结及正常乳腺组织中的表达.结果乳腺癌组织中bcl-2 mRNA表达相对值(0.264±0.137),明显高于正常乳腺组织表达相对值(0.033±0.031)(P<0.005);转移淋巴结bcl-2 mRNA表达相对值(0.272±0.076),癌旁组织bcl-2mRNA表达相对值(0.131±0.083),明显高于正常乳腺组织表达相对值(P<0.05);淋巴结转移之癌灶组bcl-2 mRNA表达相对值(0.381±0.096)明显高于非转移之癌灶组(0.186±0.102)(P<0.05).结论bcl-2基因的高表达可能在乳腺癌的发生、发展中起一定的作用.