Steroid receptors and hormones in relation to cell proliferation and apoptosis in poorly differentiated epithelial ovarian tumors.

The purpose of this study was to further investigate the role of estrogen but especially progesterone on epithelial ovarian tumor development since previous studies have suggested a relationship between serum progesterone, progesterone receptor expression and prognosis. Serum progesterone concentration, the immunohistochemical expression of estrogen receptor alpha (ER), progesterone receptor A/B (PR), Ki-67, Bcl-2, p53, apoptosis and morphology were determined in 33 patients, all with poorly differentiated surface epithelial ovarian tumors of different types. ER was expressed in 79% and PR in 33% of the tumors. This group of aggressive tumors was highly proliferative as indicated by Ki-67 index (mean 38.9%), and in some cases proliferation appeared to be mainly located to areas with a high ER density. The majority of cases (76%), both receptor-positive and -negative, overexpressed p53. High ER expression was related to a lower apoptotic activity as compared with tumors with a low expression of the ER (p = 0.008). Serum progesterone in itself did not show any clear relationship to steroid receptor status, expression of Ki-67, p53, Bcl-2 or signs of apoptosis. Survival in this small but homogeneous group of advanced epithelial ovarian cancers, showed an improved survival rate in patients with high serum progesterone, especially in combination with expression of progesterone receptors (p = 0.04). In conclusion, estrogen and progesterone receptors in parallel with deranged p53 and Ki-67 were expressed to a great extent. The finding of a lower apoptotic activity in tumors with a high expression of ER and an indication of increased proliferation in areas with high ER density gives a rationale for antiestrogen therapy even in poorly differentiated epithelial ovarian cancers. Improved survival is related to serum progesterone, especially in combination with PR expression.     

乳腺癌组织FAP表达病理生物学意义的研究

目的:探讨乳腺癌成纤维细胞活化蛋白(FAP)的表达与乳腺癌临床病理因素和生物学预后因子(ER、PR、p53、c-erbB-2、Ki-67)的相关性,评价FAP在乳腺癌的表达意义。方法:选取经病理确诊的乳腺癌患者82例,免疫组织化学法检测乳腺癌组织FAP的表达。收集乳腺癌患者的临床病理信息,分析FAP与乳腺癌临床病理因素和生物学预后因子的表达水平的关系。结果:FAP表达与患者年龄、肿瘤部位、肿瘤大小与FAP的表达无相关性(P>0.05),临床分期与FAP表达呈正相关(r=0.922,P=0.000),病理分级与FAP表达呈弱正相关,r=0.360,P=0.001。FAP表达在有无淋巴结转移组间差异统计学意义,t=11.003,P=0.00。FAP表达与p53(r=0.498,P=0.000)、c-erbB-2(r=0.326,P=0.004)、Ki-67(r=0.449,P=0.000)的表达呈正相关,FAP表达与ER、PR的表达无相关性,P>0.05。结论:FAP在女性乳腺癌发生、发展、侵袭转移方面起到了重要的作用。FAP可作为预测乳腺癌预后的重要因子。     

乳腺浸润性癌MRI表现与生物因子表达的相关性研究

目的 探讨乳腺浸润性癌MRI表现与生物因子雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER2)、肿瘤增殖抗原Ki-67、肿瘤抑制蛋白p53表达的相关性及临床意义.方法 回顾性分析69例乳腺浸润性癌患者的MRI表现及生物因子ER、PR、HER2、Ki-67、p53的表达情况,采用Spearman相关分析和分类回归树(CART)算法分析MRI表现与各生物因子表达的相关性.结果 HER2表达与淋巴结转移呈正相关(r=0.299,P﹤0.05),p53表达与病变表现为肿块呈负相关(r=-0.261,P﹤0.05);肿块分叶征象与Ki-67(r=0.472,P﹤0.01)、p53(r=0.25,P﹤0.05)阳性表达呈正相关.根据MRI表现分析各生物因子表达的CART决策树,分类准确度依次为:Ki-67(0.797)﹥ER(0.754)﹥PR(0.725)﹥HER2(0.478)﹥p53(0.464).结论 乳腺浸润性癌的MRI表现与生物因子ER、PR、HER2、Ki-67、p53的表达有一定的相关性,可作为乳腺癌的重要诊断指标.     

A comparative study of histopathology, hormone receptors, peanut lectin binding, Ki-67 immunostaining, and nucleolar organizer region-associated proteins in human breast cancer

The current study was performed on 71 cases of human female breast cancer and compares the results of five morphologic methods developed for the detection of estrogen receptors (ER), progesterone receptors (PgR), lectin Peanut agglutinin (PNA) binding sites, monoclonal antibody Ki-67 immunoreactivity, and the mean number of argyrophilic nucleolar organizer regions (Ag-NOR). All the parameters were evaluated on serial cryostat sections representative of a closely related, if not identical, neoplastic population. A significant positive correlation was found between the occurrence of estrogen, progesterone, and peanut receptors and between Ki-67 immunoreactivity, mean number of NOR, and mitotic index. Furthermore, ER, PgR, and PNA receptors showed a significant, inverse correlation with Ki-67 immunoreactivity, mitotic index, and mean number of Ag-NOR. These results provide further data that support the hypothesis that (1) progesterone and PNA receptors are estrogen-induced and indicate a metabolic response of the target cells to functioning estrogen receptors; (2) the mean number of NOR reflects the cell kinetics of the tumor; and (3) metabolic differentiation of neoplastic cells is inversely correlated to the proliferation index.     

Low-dose medical radiation exposure and breast cancer risk in women under age 50 years overall and by estrogen and progesterone receptor status: results from a case–control and a case–case comparison

Although moderate to high-dose ionizing radiation exposure is an established risk factor for breast cancer, the effect of low-dose radiation exposure has not been clarified by epidemiological data. We evaluated the effect of low-dose radiation from medical procedures on risk of breast cancer overall and by joint estrogen and progesterone receptor (ER/PR) status in 1,742 population-based case patients aged 20–49 years and 441 control subjects identified from neighbourhoods of case patients in Los Angeles County. After excluding radiation exposures in the 5 years prior to case’s diagnosis or control’s initial household contact date we found an elevated breast cancer risk among women who reported having had multiple chest X-rays (P _trend = 0.0007) or 7 or more mammograms (odds ratio [OR] = 1.80, 95% confidence interval [CI] = 0.95–3.42). Risk was also increased among women who received dental X-rays without lead apron protection before age 20 years (OR = 1.81, 95% CI = 1.13–2.90). Women, who had their first exposure to these medical radiation procedures during childhood, had a greater increase in risk than those who were first exposed at older ages. Although not statistically significantly different, risk estimates were somewhat stronger for nulliparous than for parous women. We found no effect modification by ER/PR status. In conclusion, our findings support the hypothesis that low-dose ionizing radiation, and particularly exposures during childhood, increase breast cancer risk.     

Hexokinase and phosphofructokinase activity and intracellular distribution correlate with aggressiveness and invasiveness of human breast carcinoma

Glycolytic enzymes, such as hexokinase and phosphofructokinase, have been reported to be upregulated in many cancer types. Here, we evaluated these two enzymes in 54 breast cancer samples collected from volunteers subjected to mastectomy, and the results were correlated with the prognosis markers commonly used. We found that both enzymes positively correlate with the major markers for invasiveness and aggressiveness. For invasiveness, the enzymes activities increase in parallel to the tumor size. Moreover, we found augmented activities for both enzymes when the samples were extirpated from patients presenting lymph node involvement or occurrence of metastasis. For aggressiveness, we stained the samples for the estrogen and progesterone receptors, HER-2, p53 and Ki-67. The enzyme activities positively correlated with all markers but Ki-67. Finally, we conclude that these enzymes are good markers for breast cancer prognosis.     

乳腺癌组织磷酸化Akt表达及其与临床生物学因素的相关性研究

目的:研究乳腺癌组织磷酸化Akt(pAkt)表达与人表皮生长因子受体-2(HER-2)、雌激素受体(ER)和孕激素受体(PR)状态及临床病理特征之间的关系。方法:收集导管原位癌16例和浸润性导管癌70例,免疫组织化学方法检测pAkt、HER-2、ER、PR、p53和Ki-67表达,统计分析其相关性,以及pAkt与患者临床特征的关系。结果:导管原位癌组织pAkt阳性率为0(0/16),浸润性导管癌组织为38.6%(27/70),差异有统计学意义,P=0.003。导管原位癌组织中pAkt水平与HER-2的表达无相关性。70例浸润性乳腺癌组织pAkt水平在HER-2阴性组(18.8%,6/32)、不确定组(37.5%,6/16)和阳性组(68.2%,15/22)间差异有统计学意义,P=0.000。淋巴结转移组和未转移组中pAKT的阳性表达也差异有统计学意义,P=0.009。结论:pAkt在浸润性导管癌组织中的表达频率显著高于导管原位癌,其表达水平与HER-2的表达水平呈正相关,并可能与肿瘤淋巴结转移的发生有关。     

乳腺浸润性导管癌组织Ki-67表达及其分子分型的意义

目的:探讨Ki-67增殖抗原在乳腺浸润性导管癌组织中的表达及与临床病理特征、雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体-2(C-erbB-2)和抑癌基因p53的关系.方法:采用Elivison二步法进行免疫组化染色,检测102例单侧乳腺浸润性导管癌组织中Ki-67、ER、PR、C-erbB-2和p53的表达水平,并结合患者相关临床资料进行分析.结果:Ki-67高表达(≥14％)比例占82.4％ (84/102).不同分子亚型中,luminalA型Ki-67表达率最低,三阴性(导管)最高.Ki-67表达水平与单侧浸润性导管癌患者的淋巴结转移(x2=5.007,P=0.025)、TNM分期(u=705.000,P=0.032)和组织分级(单侧Fisher:P=0.042)有明显的相关性,与患者的年龄(t=1.996,P=0.052)、肿块大小(u=859.000,P=0.502)和侵犯脉管情况(xc2=0.762,P=0.383)无明显的相关性.Ki-67表达水平与ER(r=-0.273,P=0.005)、PR(r=-0.332,P=0.001)表达程度呈负相关;与C-erbB-2(r=0.327,P=0.001)、p53(r=0.343,P=0.000)表达程度呈正相关.结论:Ki-67表达与目前乳腺癌分子分型相关,其高表达是预后不良因素.     

Environmental factors in relation to breast cancer characterized by p53 protein expression.

Findings from studies of cigarette smoking and low-dose ionizing radiation exposure and breast cancer are unclear. Laboratory studies indicate that both exposures can cause DNA damage, potentially increasing cancer risk if such mutations occur in growth control genes, such as p53. We examined the potential etiologic heterogeneity of breast cancer by evaluating whether associations between cigarette smoking and low-dose ionizing radiation and breast cancer differed by p53 protein expression status. Data were obtained from the Carolina Breast Cancer Study, a population-based, case-control study conducted among African-American and white women ages 20-74 years. Questionnaire data were available from 861 women with incident, primary invasive breast cancer and 790 community-based controls. p53 immunostaining was performed on tissue from 683 women with breast cancer; 46% were classified as p53+. Two separate unconditional logistic regression models were used to calculate odds ratios (ORs) for p53+ and p53- breast cancer, as compared with controls, in relation to smoking and low-dose ionizing radiation exposure. Smoking was not differentially associated with p53+ or p53- breast cancer, even when duration, dose, and passive smoking status were considered. Exposure to individual sources of radiation did not differ for p53+ and p53- breast cancers. However, ORs for combined exposure to chest X-rays and occupational radiation were higher for p53+ [OR, 2.2; 95% confidence interval (CI), 1.0-5.3] than p53- breast cancer (OR, 1.2; 95% CI, 0.5-3.4). Combined exposure to radiation from other medical sources as well as occupational exposure was also higher for p53+ (OR, 3.7; 95% CI, 0.8-16.8) than for p53- breast cancer (OR, 1.7; 95% CI, 0.3-10.5). Although preliminary, our results suggest that exposure to multiple sources of low-dose ionizing radiation may contribute to the development of p53+ breast cancer.     

CCDC8基因在乳腺癌中的表达

目的 探讨CCDC8在乳腺癌组织中的表达及其与乳腺癌临床病理特征的关系.方法 采用定量反转录聚合酶链反应（qRT-PCR）分析CCDC8在40例乳腺癌组织和22例良性乳腺肿瘤组织中的表达情况;以及CCDC8的表达与年龄、肿块大小、临床分期、雌激素受体（ER）、孕激素受体（PR）、CerbB2、p53 、Ki-67、nm23之间的关系.结果 CCDC8基因在乳腺良性肿瘤中的表达量（1685±755）明显高于乳腺癌组织中的表达量（502.1±223.2）;CCDC8基因的表达量在年龄＞50岁（789.8±367）乳腺癌组织中的表达高于年龄≤50岁（452.5±170.3）的乳腺癌组织;CCDC8的表达与ER、PR、CerbB2、p53、Ki-67、临床分期之间差异无统计学意义（P＞ 0.05）;CCDC8的表达与nm23的表达差异有统计学意义（P=0.044）;CCDC8与nm23呈负相关（Correlation Coegicient=-0.400,P=0.039＜ 0.05）.结论 CCDC8在乳腺肿瘤组织中有表达,恶性组织表达量低于良性组织,CCDC8的表达与年龄、肿块大小、nm23有相关性,CCDC8可能是乳腺癌的一个抑癌基因影响乳腺癌的发生、发展.     

新辅助化疗对乳腺癌ER PR HER-2及Ki-67表达影响的研究进展

目前乳腺癌已成为女性发病率最高的恶性肿瘤,新辅助化疗（neoadjuvant chemotherapy,NAC）后雌激素受体（estrogen receptor,ER）、孕激素受体（progesterone receptor,PR）和人表皮生长因子受体-2（human epidermal growth factor receptor-2,HER-2）、Ki-67表达情况会有不同程度变化,这种变化机制是否会影响后续治疗方案的选择尚无定论。本文将就NAC对乳腺癌ER、PR、HER-2及Ki-67表达影响的研究进展进行综述。      

Estrogen and progesterone regulate radiation-induced p53 activity in mammary epithelium through TGF-beta-dependent pathways

DNA damage normally induces p53 activity, but responses to ionizing radiation in the mammary epithelium vary among developmental stages. The following studies examined the hormones and growth factors that regulate radiation-responsiveness of p53 in mouse mammary epithelium. Immunoreactive p21/WAF1 and TUNEL staining were used as indicators of p53 activity following exposure to ionizing radiation. In ovariectomized mice, radiation-induced accumulation of p21/WAF1 was minimal in the mammary epithelial cells (<1%). Systemic injections of estrogen and progesterone (E+P) for 72 h were necessary to recover maximal expression of p21/WAF1 following ionizing radiation (55%). The effects of E+P on radiation-induced p21/WAF1 were p53-dependent as responses were absent in Trp53-/- mice. Though hormonal treatments stimulated increases in the proportion of cycling cells (PCNA-positive), this was not directly correlated with p53 activity. Whole organ cultures were used to determine whether E+P act directly upon the mammary gland. Treatment with E+P was sufficient to render p53 responsive to radiation, but TGF-beta-neutralizing antibodies blocked responsiveness. In the absence of E+P, TGF-beta1 alone did not alter p53 activity. These results demonstrate that estrogen and progesterone together with TGF-beta signaling are necessary for maintenance of p53 activity in the mammary epithelium.     

新辅助化疗对乳腺癌患者survivin、Ki-67、ER、C-erbB-2、p53和肿瘤组织学分级的影响及其疗效预测意义

目的探讨新辅助化疗对乳腺癌survivin、Ki-67、ER、C-erbB-2、p53和肿瘤组织学分级的影响,同时研究这些指标对新辅助化疗的疗效预测作用。方法通过免疫组织化学S-P法检测和HE染色对化疗前空芯针穿刺标本和化疗后手术切除的30例乳腺癌组织的survivin、Ki-67、ER、C-erbB-2、p53和肿瘤组织学分级的表达情况。化疗方案为CAF（CTX 600 mg/m^2,THP 50 mg/m2,5-FU500 mg/m^2）和TA（艾素75 mg/m^2,THP 30 mg/m^2）,每3周1疗程,用药2～3个疗程。化疗疗效通过采用临床体检、乳腺彩超检测及术后病理分析综合判断。结果 30例患者中70.0%（21/30）获PR,SD为30.0%（9/30）,全组无恶化病例,总有效率为70.0%（21/30）。通过对化疗前后的指标比较发现：新辅助化疗能降低Ki-67的表达（P〈0.01）和肿瘤分级（P〈0.05）。化疗前后survivin、ER、C-erbB-2和p53表达无明显变化（P〉0.05）。Ki-67高表达（≥20%）、肿瘤分级高的患者和Ki-67低表达（〈20%）、肿瘤分级较低的患者相比,化疗疗效更明显（P〈0.05）。结论新辅助化疗能显著降低乳腺癌组织Ki-67的表达和肿瘤分级,而对survivin、ER、C-erbB-2和p53表达均无显著影响,Ki-67高表达（≥20%）、肿瘤分级高的患者对化疗更敏感、短期疗效更显著。     

Steroid-hormone production and receptors in relation to ki-67, p53, s-phase fraction and ploidy in epithelial ovarian-tumors

In this investigation, the in vitro production of progesterone and estradiol in ovarian tissues was studied for the first time in relation to the immunohistochemical expression of steroid hormone receptors, Ki-67, p53, DNA ploidy and S-phase fraction. Ovarian tissue from 44 women was examined. Steroid receptors were found more frequently in normal than in tumor ovaries. A substantial focal staining heterogeneity was demonstrated. Mucinous tumors were always progesterone receptor negative. Furthermore, the Ki-67 index was negatively correlated to the progesterone production of the tumor ovaries. Among the malignant tumors, all the high producers of progesterone expressing PR were low proliferating, diploid and p53-negative.     

CD147和Ki-67在甲状腺乳头状癌中的表达及意义

目的:探讨甲状腺乳头状癌组织中CD147和Ki-67表达情况及临床意义。方法:应用免疫组化法检测甲状腺乳头状癌、滤泡性腺瘤和正常甲状腺组织（各50例）中CD147和Ki-67的表达。结果:甲状腺乳头状癌组织中CD147阳性表达率明显高于滤泡性腺瘤和正常甲状腺组织（68％ vs 20% vs 0）,三者比较差异有统计学意义（P<0.001）。CD147表达与淋巴结转移和TNM分期有关（P<0.05）。正常甲状腺组织中Ki-67未见阳性表达,甲状腺乳头状癌、滤泡性腺瘤中阳性表达率为（36％ vs 18%）,三者比较差异有统计学意义（P<0.05）。结论:CD147和Ki-67表达异常是甲状腺乳头状癌产生的机制之一,与甲状腺乳头状癌的发生及发展有关。CD147可能是甲状腺乳头状癌预后的一项重要预测指标。     

新辅助化疗对乳腺癌患者Ki-67、ER、Her-2和p53的影响及意义

目的探讨新辅助化疗(neoadjuvant chemotherapy,NAC)对乳腺癌Ki-67、ER、Her-2和p53的影响,同时研究上述指标对NAC疗效的预测作用。方法通过免疫组化S-P法检测化疗前经空芯针穿刺标本和化疗后手术切除的30例乳腺癌组织标本的Ki-67、ER、Her-2和p53的表达情况。具体化疗方案为:CAF(CTX600mg/m2,ADM50mg/m2,5-Fu500mg/m2)和TA(艾素75mg/m2,THP30mg/m2),每3周为1疗程,用药2～3个疗程。化疗疗效通过临床体检、乳腺彩超检测及术后病理分析综合判断。结果 30例患者中70%(21/30)获PR,30%(9/30)获SD,全组无恶化病例,总有效率为70%(21/30)。通过对化疗前后各指标的比较发现:NAC能降低Ki67的表达(P<0.01)。化疗前后ER、Her-2和p53表达无明显变化(P>0.05)。Ki67高表达(≥20%)、ER阴性表达及突变型p53阳性表达患者的化疗疗效更明显(P<0.05)。结论 NAC能显著降低乳腺癌组织Ki-67的表达,而对ER、Her-2和p53表达均无显著影响,Ki-67高表达(≥20%)、ER阴性及突变型p53阳性表达的患者对化疗更敏感、短期疗效更显著。     

Prognostic Significance of Circulating Tumor Cells and SerumCA15-3 Levels in Metastatic Breast Cancer,Single CenterExperience,Preliminary Results

Background: Breast cancer is the second leading cancer causing death in women. Circulating tumor cellsare among the prognostic factors while tumor markers are of diagnostic value and can be used for follow-up.The aim of this study was to investigate the correlation between the prognostic significance of the serum CA15-3levels, number of circulating tumor cells and histopathological tumor factors. Materials and Methods: Thirtypatients recently diagnosed with breast cancer were included in the study. Number of circulating tumor cells andserum CA15-3 level were assessed when metastasis was detected and diagnostic value was assessed. Presence ofassociations with estrogen and progesterone receptors, c-erbB2, Ki-67 proliferation index and histological gradewere also evaluated. Results: Median overall survival of the patients with serum CA15-3 levels of >108 ng/dlwas 19 months whereas for those with a low serum level it was 62 months. Median overall survival for CTC≥5vs CTCConclusions: Prognostic significance of the CTC count and CA15-3 levels in metastaticbreast cancer patients was demonstrated.     

Normal tissue response to low doses of radiotherapy assessed by molecular markers--a study of skin in patients treated for prostate cancer

The aim of this study was to evaluate normal tissue response by molecular markers to multifraction low doses of ionizing radiation, with the focus on changes in repopulation, estimated using Ki-67 as the proliferation marker, and on expressions of the p53 and p21 proteins, identified as key proteins in the DNA damage checkpoint. Repeated skin biopsies were taken from patients treated for prostate cancer with radiotherapy. The expressions of Ki-67, p53 and p21 of the keratinocytes in the basal cell layer of the epidermis were quantified immunohistochemically. The dose to the basal layer was 1.1 Gy per fraction, given five times per week for seven weeks. The indices of the three markers were determined over the whole period. A significant suppression of the Ki-67 index was observed during the first weeks, followed by a significant gradual increase in the Ki-67 index over the last weeks. The p53 and p21 protein levels were almost zero in the unirradiated skin. Upon irradiation, both the p53 and p21 index increased in a pattern very congruent to the Ki-67 index. In conclusion, daily fractions of about 1 Gy to the skin resulted in, for the keratinocytes in the basal layer, a cell growth arrest for a couple of weeks and a subsequent acceleration in repopulation during the following weeks of irradiation. The present findings also provided novel insights into the role of the p53/p21 pathway in the response of a normal epithelium to ionizing radiation as it is applied in radiotherapy.     

Activated Akt signaling pathway in invasive ductal carcinoma of the breast: correlation with HER2 overexpression

Akt/PKB is a serine/threonine kinase that plays a crucial role in cell survival and apoptosis. Aberrant activation of pAkt is associated with various malignant human cancers, including breast carcinoma. In vitro studies show that pAkt activation is mediated by estrogen and acts as a downstream effector of HER2 with implications in breast cancer progression and drug resistance. We investigated the incidence of Akt activation in invasive ductal carcinoma and its correlation with other clinicopathological variables. Using tissue microarray technology, immunohistochemical expression of phosphorylated Akt (pAkt) at Ser-473 was evaluated in 127 cases of invasive ductal carcinomas, together with hormone receptors, HER2, p53, Ki-67 and other clinicopathological variables. Both nuclear and cytoplasmic expression was noted for pAkt, with 46 cases (36.2%) showing high cytoplasmic pAkt expression and 37 cases (29.1%) showing high nuclear pAkt expression. There was a significant association between both high cytoplasmic and nuclear pAkt expression with HER2 overexpression (both p<0.0001). There was also a positive correlation between high nuclear pAkt expression with both estrogen receptor and progesterone receptor status (p=0.042 and p=0.015, respectively). High cytoplasmic pAkt expression was associated with high Ki-67 expression (p=0.052), however, there was no association between pAkt and p53 expression. In the present study, activation of the Akt pathway shows strong association with HER2 overexpression, which is consistent with many in vitro studies. Our study also showed a positive correlation between pAkt and hormone receptors, which suggested the possible mechanism of endocrine resistance in ER-positive breast cancer. These results also suggest the prognostic value of pAkt and its importance in the prediction of therapeutic response in invasive ductal carcinoma of the breast.     

Expression of cell cycle regulatory proteins in breast carcinomas before and after preoperative chemotherapy

Molecular markers predicting response to preoperative chemotherapy would be of major clinical relevance in breast cancer. Therefore, we studied the relationship between the expression of cell cycle regulatory proteins and clinical outcome in breast cancer patients receiving preoperative chemotherapy. Expression of p21^Waf1, p27^Kip1, p53, cyclin D3 and Ki-67 was determined in breast carcinomas by means of immunohistochemistry both prior and after preoperative chemotherapy. Expression data were compared with both clinical parameters and response to preoperative chemotherapy with either cyclophosphamide/methotrexate/5-fluorouracil (CMF, n = 29) or epirubicin/docetaxel (ED, n = 36). In paired samples before and after preoperative chemotherapy, the percentage of p21^Waf1, p27^Kip1, p53 and cyclin D3 positive nuclei of tumor cells in postchemotherapy specimens was significantly higher than the percentage in prechemotherapy samples but no change in Ki-67 expression was observed. High Ki-67 expression (p = 0.02), negative estrogen receptor status (p = 0.01) and negative progesterone receptor status (p = 0.04) were associated with complete pathologic response to chemotherapy, whereas the other markers did not predict response. In conclusion, expression levels of p21^Waf1, p27^Kip1, p53 and cyclin D3 significantly increased after preoperative chemotherapy in breast carcinomas but only high Ki-67 expression, negative estrogen receptor status and negative progesterone receptor status were associated with complete pathologic response to preoperative chemotherapy.