不同分子分型乳腺癌患者血清IGFBP-3、Angptl-2表达水平及其与骨转移、预后的相关性

摘要 目的：分析不同分子分型乳腺癌患者血清胰岛素样生长因子结合蛋白3（IGFBP-3）、生成素养蛋白2（Angptl-2）表达水平及其与骨转移、预后的相关性。方法：选取2018年3月-2021年3月东南大学附属中大医院收治的128例乳腺癌骨转移患者进行研究,其中包括Luminal A型50例、42例Luminal B型（HER-2阴性）42例、HER-2过表达型16例、三阴性乳腺癌（TNBC）20例,并分析4种分子分型乳腺癌的临床病理特征,同时采用酶联免疫吸附法检测其血清IGFBP-3、Angptl-2表达水平;随访24个月后记录两组患者的预后情况,并采用多因素Logistic模型分析影响4种分子分型乳腺癌骨转移患者预后的独立危险因素,以及血清IGFBP-3、Angptl-2与不同分子分型乳腺癌骨转移患者预后的相关性。结果：Luminal A型、Luminal B型、HER-2过表达型、TNBC型TNM分期、淋巴结转移比较,差异有统计学意义（P＜0.05）。与Luminal A型、Luminal B型、TNBC型乳腺癌骨转移患者相比,HER-2过表达型乳腺癌骨转移患者的血清IGFBP-3表达水平较低,Angptl-2表达水平较高（P＜0.05）。Luminal A型、Luminal B型、HER-2过表达型、TNBC型乳腺癌骨转移患者的死亡率分别为13.46%、38.46%、23.08%、25.00%。多因素Logistic结果显示,TNM分期、淋巴结转移、血清IGFBP-3、Angptl-2均是影响不同分子分型乳腺癌骨转移患者预后的独立危险因素（P＜0.05）。血清IGFBP-3异常高表达提示4种分子分型乳腺癌骨转移患者的不良预后,而Angptl-2表达水平与4种分子分型乳腺癌的预后呈正相关性（P＜0.05）。针对不同分子分型乳腺癌骨转移患者的预后预测中,血清IGFBP-3、Angptl-2、IGFBP-3+Angptl-2均呈现AUC＞0.75。结论：血清IGFBP-3、Angptl-2可作为HER-2过表达乳腺癌骨转移患者的潜在生物标志物;同时还可根据血清IGFBP-3、Angptl-2表达水平预测不同分子分型乳腺癌骨转移患者的预后。     

HIF1A-AS2 predicts poor prognosis and regulates cell migration and invasion in triple-negative breast cancer

The aberrant expression of hypoxia-inducible factor 1 alpha (HIF1A)-antisense RNA 2 (HIF1A-AS2) was found in various human cancers including breast cancer. The aim of this study was to present more evidence about the role HIF1A-AS2 on triple-negative breast cancer (TNBC). In our results, HIF1A-AS2 was also found to be upregulated in TNBC tissues compared with non-TNBC tissues or adjacent normal tissues. Besides, HIF1A-AS2 expression was also elevated in TNBC cell lines compared with the normal breast epithelial cell line. Moreover, high expression of HIF1A-AS2 was associated with lymph node metastasis, distant metastasis and unfavorable histological grade in TNBC patients. Survival analysis showed a TNBC patient with high HIF1A-AS2 expression had shorter overall survival than patients with low HIF1A-AS2 expression, and HIF1A-AS2 high expression acted as an independent poor prognostic factor for overall survival in TNBC patients. The cell migration and invasion assays suggested inhibition of HIF1A-AS2 obviously depressed TNBC cell migration and invasion. In conclusion, HIF1A-AS2 serves as a novel biomarker for predicting clinical progression and prognosis in TNBC.     

Clinical prognostic evaluation of immunocytes in different molecular subtypes of breast cancer

To retrospectively analyze the relationship between preoperative blood parameters and postoperative clinical outcomes in patients with different molecular subtypes of breast cancer (BC), a cohort of 601 patients with BC in the Third Affiliated Hospital, Sun Yat-sen University, was retrospectively reviewed. They were categorized into four subtypes according to the expression of ER, PR, HER-2, and KI-67%. White blood cell, neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet counts, the neutrophil-to-lymphocyte ratio (NLR), the neutrophil-to-monocyte ratio (NMR), the lymphocyte-to-monocyte ratio (LMR), and the platelet-to-lymphocyte ratio (PLR) were recorded. Univariate and multivariate analyses were performed to identify the relationship between parameters and ratios and disease-free survival (DFS) and overall survival (OS). Luminal subtypes of BC had smaller tumor volume, better differentiation degree of invasive ductal carcinoma, less lymph node metastasis, and better clinical outcome than the HER-2 overexpression and triple-negative BC (TNBC) subtypes. In multivariate analysis, age and LMR were the independent prognostic factors of DFS in patients with luminal A (age, p = 0.005; LMR, P = 0.026); PLR in patients with luminal B (DFS; p = 0.032; OS, p= 0.012); LMR in patients with HER-2 overexpression (DFS; p = 0.008; OS, p = 0.017); and NLR for DFS (p = 0.014); and WBC for OS (p = 0.008) in patients with TNBC. LMR was the benign predictor of luminal A and HER-2 overexpression. PLR was the adverse predictor of luminal B. WBC and NLR were the adverse predictors of TNBC. Therefore, these peripheral blood parameters can play an important role in the diagnosis and treatment of patients with different molecular subtypes of BC.     

miR‐655 suppresses epithelial‐to‐mesenchymal transition by targeting Prrx1 in triple‐negative breast cancer

Triple‐negative breast cancer (TNBC) is a highly aggressive breast cancer subtype that lacks effective targeted therapies. The epithelial‐to‐mesenchymal transition (EMT) is a key contributor in the metastatic process. In this study, we found that miR‐655 was down‐regulated in TNBC, and its expression levels were associated with molecular‐based classification and lymph node metastasis in breast cancer. These findings led us to hypothesize that miR‐655 overexpression may inhibit EMT and its associated traits of TNBC. Ectopic expression of miR‐655 not only induced the up‐regulation of cytokeratin and decreased vimentin expression but also suppressed migration and invasion of mesenchymal‐like cancer cells accompanied by a morphological shift towards the epithelial phenotype. In addition, we found that miR‐655 was negatively correlated with Prrx1 in cell lines and clinical samples. Overexpression of miR‐655 significantly suppressed Prrx1, as demonstrated by Prrx1 3′‐untranslated region luciferase report assay. Our study demonstrated that miR‐655 inhibits the acquisition of the EMT phenotype in TNBC by down‐regulating Prrx1, thereby inhibiting cell migration and invasion during cancer progression.     

乳腺癌细胞hMSH2 蛋白、CD4、CD8的表达及其与淋巴结转移的关系

目的:探讨乳腺癌细胞hMSH2蛋白、CD4和CD8表达与淋巴结转移的关系及临床意义.方法:采用免疫组织化学方法检测49例乳腺癌(淋巴结转移25例,无淋巴结转移24例)患者癌细胞hMSH2蛋白、CD4和CD8的表达,并分析其表达与淋巴结转移的关系.结果:hMSH2蛋白在乳腺癌细胞细胞核内表达,CD4和CD8在乳腺癌细胞细胞浆和细胞膜表达.淋巴结转移组与无淋巴结转移组hMSH2蛋白、CD4和CD8的表达率分别为29%和68%(P＜0.05)、58%和44%(P＞0.05)、29%和68%(P＜0.05).结论:在有淋巴结转移的乳腺癌细胞hMSH2蛋白、CD4、CD8表达的改变可能与乳腺癌淋巴结转移有关.     

Up-Regulation of RFC3 Promotes Triple Negative Breast Cancer Metastasis and is Associated With Poor Prognosis Via EMT

Triple-negative breast cancer (TNBC) was regarded as the most aggressive and mortal subtype of breast cancer (BC) since the molecular subtype system has been established. Abundant studies have revealed that epithelial-mesenchymal transition (EMT) played a pivotal role during breast cancer metastasis and progression, especially in TNBC. Herein, we showed that inhibition the expression of replication factor C subunit 3 (RFC3) significantly attenuated TNBC metastasis and progression, which was associated with EMT signal pathway. In TNBC cells, knockdown of RFC3 can down-regulate mesenchymal markers and up-regulate epithelial markers, significantly attenuated cell proliferation, migration and invasion. Additionally, silencing RFC3 expression can decrease nude mice tumor volume, weight and relieve lung metastasis in vivo. Furthermore, we also demonstrated that overexpression of RFC3 in TNBC showed increased metastasis, progression and poor prognosis. We confirmed all of these results by immunohistochemistry analysis in 127 human TNBC tissues and found that RFC3 expression was significantly associated with poor prognosis in TNBC. Taken all these findings into consideration, we can conclude that up-regulation of RFC3 promotes TNBC progression through EMT signal pathway. Therefore, RFC3 could be an independent prognostic factor and therapeutic target for TNBC.     

Molecular type and maximal metastasis diameter influence risk of axillary recurrence in breast cancer patients after positive sentinel lymph node biopsy

BackgroundBreast cancer patients with positive sentinel lymph node biopsy (SLNB) may be spared axillary lymph node dissection (ALND) in favour of irradiation. The aim of the study was to estimate local control probability in the axilla (axLCP).Materials and methodsWe identified 1832 invasive breast cancer patients who had undergone SLNB at our centre. We measured maximal metastasis diameter (SLDmax) in the sentinel lymph nodes and lymph node metastasis volume (VALN) from ALND in 246 patients with one or two positive SLNs. We calculated axLCP after irradiation and systemic treatment for different molecular types.ResultsVALN values are higher for high grade tumours and larger metastases in SLNs (> 5 mm). It is smaller in luminal A tumours. axLCP is high, nearly 100%, in all molecular types in radiation sensitive tumours (SF2 Gy = 0.45), except luminal B. Expected axLCP is relatively low (67%) in luminal B radiation sensitive tumours with no chemotherapy and nearly 100% with chemotherapy.ConclusionVALN values differ among molecular tumour types. They depend on SLNDmax and tumour grade. New prognostic factors are needed for selected luminal B breast cancer patients (i.e. high grade tumours, large metastases in SLNs) after positive SLNB intended to be spared ALND and chemotherapy.     

Clinicopathological Features and Prognosis of Metaplastic Breast Carcinoma: Experience of a Major Chinese Cancer Center

Metaplastic breast carcinoma (MBC) is a rare heterogeneous group of primary breast malignancies, with low hormone receptor expression and poor outcomes. To date, no prognostic markers for this tumor have been validated. The current study was undertaken to evaluate the clinicopathologic characteristics, the response to various therapeutic regimens and the prognosis of MBCs in a large cohort of patients from Tianjin Medical University Cancer Hospital in China. Ninety cases of MBCs diagnosed in our hospital between January 2000 and September 2014 were retrieved from the archives. In general, MBCs presented with larger size, a lower rate of lymph node metastasis, and demonstrated more frequent local recurrence/distant metastasis than 1,090 stage-matched cases of invasive carcinoma of no specific type (IDC-NST), independent of the status of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expressions. The five-year disease-free survival (DFS) of MBC was significantly worse than IDC-NST. Using univariate analysis, lymph node metastasis, advanced clinical stage at diagnosis, high tumor proliferation rate assessed by Ki-67 labeling, and epidermal growth factor receptor (EGFR) overexpression/gene amplification were associated significantly with reduced DFS, while decreased OS was associated significantly with lymph node metastasis and EGFR overexpression/gene amplification. With multivariate analysis, lymph node status was an independent predictor for DFS, and lymph node status and EGFR overexpression/gene amplification were independent predictors for OS. Histologic subtyping and molecular subgrouping of MBCs were not significant factors in prognosis. We also found that MBCs were insensitive to neoadjuvant chemotherapy, routine chemotherapy, and radiation therapy. This study indicates that MBC is an aggressive type of breast cancer with poor prognosis, and that identification and optimization of an effective comprehensive therapeutic regimen is needed.     

组织蛋白酶D和nm23基因蛋白在乳腺癌中的表达及与淋巴结转移的关系

采用免疫组织化学 ABC法检测了 43例乳腺癌中的组织蛋白酶 D和 nm 2 3基因蛋白的表达。结果显示组织蛋白酶D在乳腺癌组织中表达阳性率为 76 .7% (33/43)。 43例乳腺癌中 2 5例伴有淋巴结转移 ,18例无淋巴结转移 ,其组织蛋白酶D表达阳性率分别为 92 % (2 3/2 5 )及 5 5 .6 % (10 /18) ,两者之间具有显著性差异 (P<0 .0 1)。 nm 2 3基因蛋白在 43例乳腺癌中阳性率为 72 .1% (31/43)。在有淋巴结转移和无淋巴结转移的乳腺癌中 nm2 3基因蛋白阳性率分别为 6 0 % (15 /2 5 )及80 .9% (16 /18) ,nm2 3基因蛋白的表达与淋巴结转移呈显著负相关 (P<0 .0 5 )。结果提示对乳腺癌根治术后无淋巴结转移 ,但组织蛋白酶 D表达阳性 ,nm2 3基因蛋白表达阴性的患者 ,可能具有潜在的复发和转移倾向 ,应多加关注 ,并密切随访。     

Triple Negative Breast Tumors in African-American and Hispanic/Latina Women Are High in CD44+, Low in CD24+, and Have Loss of PTEN

Background

African-American women have higher mortality from breast cancer than other ethnic groups. The association between poor survival and differences with tumor phenotypes is not well understood. The purpose of this study is to assess the clinical significance of (1) Stem cell-like markers CD44 and CD24; (2) PI3K/Akt pathway associated targets PTEN, activation of Akt, and FOXO1; and (3) the Insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP3) in different breast cancer subtypes, and compare the differences between African-American and Hispanic/Latina women who have similar social-economic-status.

Methods

A total of N=318 African-American and Hispanic/Latina women, with clinically-annotated information within the inclusion criteria were included. Formalin fixed paraffin embedded tissues from these patients were tested for the different markers using immunohistochemistry techniques. Kaplan-Meier survival-curves and Cox-regression analyses were used to assess Relative Risk and Disease-Free-Survival (DFS).

Results

The triple-negative-breast-cancer (TNBC) receptor-subtype was more prevalent among premenopausal women, and the Hormonal Receptor (HR) positive subtype was most common overall. TNBC tumors were more likely to have loss of PTEN, express high Ki67, and have increased CD44+/CD24- expression. TNBC was also associated with higher plasma-IGF-I levels. HR-/HER2+ tumors showed high pAkt, decreased FOXO1, and high CD24+ expression. The loss of PTEN impacted DFS significantly in African Americans, but not in Hispanics/Latinas after adjusted for treatment and other tumor pathological factors. The CD44+/CD24- and CD24+/CD44- phenotypes decreased DFS, but were not independent predictors for DFS. HER2-positive and TNBC type of cancers continued to exhibit significant decrease in DFS after adjusting for the selected biomarkers and treatment.

Conclusions

TNBC incidence is high among African-American and Hispanic/Latino women residing in South Los Angeles. Our study also shows for the first time that TNBC was significantly associated with PTEN loss, high Ki67 and the CD44+/CD24- phenotype. The loss of PTEN impacts DFS significantly in African Americans.     

Fas 相关死亡结构域蛋白在乳腺癌中表达的临床病理研究

目的:探讨Fas相关死亡结构域蛋白(Fas-associated death domain protein,FADD)在乳腺癌中表达的临床病理学意义。方法:收集乳腺癌病例及相应的临床资料包括随访资料,应用免疫组织化学技术检测乳腺良性病变,有/无淋巴结转移的乳腺癌及配对淋巴结转移灶中FADD的表达,观察分析FADD表达与乳腺癌患者年龄、肿块大小、临床分期、组织学类型和分级、雌孕激素受体水平等临床病理指标间的关系。结果:免疫组化检测结果显示良性乳腺病变组中FADD的阳性表达率(85.1%,40/47)与无淋巴结转移的乳腺癌组(45.8%,38/83),伴有淋巴结转移的乳腺癌组(67.3%72/107)和淋巴结转移灶(45.8%,49/107)组织中FADD阳性表率均有显著性差异(P值分别0.001,=0.022和0.001);此外,伴有淋巴结转移的乳腺癌组中FADD阳性表达率也均与其它三组中FADD阳性表达率之间具有显著性差异(P值分别为0.003,0.001和0.022)。FADD与患者的确诊年龄(P=0.049)和淋巴结转移有显著性相关(P=0.003),与肿瘤大小、临床分期、组织学类型、组织学分级、雌孕激素受体及cerb B-2的表达情况和月经史无明显相关性(P0.05)。生存分析显示FADD阳性表达的患者较FADD阴性患者的生存期更短。结论:FADD与乳腺癌淋巴结转移和预后有关。     

LIPH promotes metastasis by enriching stem‐like cells in triple‐negative breast cancer

Lipase member H (LIPH), a novel member of the triglyceride lipase family. The clinical implications of its expression in breast cancer are still unclear. Therefore, in this study, we investigated the associations between LIPH and the tumorigenic behaviours of 144 triple‐negative breast cancer (TNBC) patients. The ratio and mammosphere‐forming ability of CD44+/CD24? stem‐like cells were tested. The role of LIPH in breast cancer cell migration and invasion was also evaluated. In addition, the effect of LIPH silencing on mitochondrial respiration was determined using the Seahorse assay. Finally, the effect of LIPH silencing on protein expression was determined via tandem mass tag‐based spectrometry and Western blotting. We found that LIPH expression was associated with metastasis in lymph nodes and distant organs (P = 0.025), resulting in poor survival among breast cancer patients (P = 0.027). LIPH knockdown significantly decreased both the ratio of CD44⁺/CD24^? stem‐like cells and their mammosphere‐forming ability. LIPH silencing promoted apoptosis, arrested cell cycle in the G2/M phase, mitigated the oxidation‐related oxygen consumption rate in the mitochondria, and reduced metabolism. LIPH inhibited adhesion between tumour cells and enhanced the epithelial‐mesenchymal transition. Tandem mass spectrometric analysis presented 68 proteins were differentially expressed in LIPH‐silenced cells and LIPH‐mediated modulation of tumour cell adhesion depended on integrin‐related CAPN2 and paxillin signalling. Overall, our findings provided strong evidence that LIPH up‐regulation promoted metastasis and the stemness of TNBC cells. Therefore, targeting LIPH is a potentially viable strategy for preventing metastasis in TNBC.     

Beyond Axillary Lymph Node Metastasis,BMI and Menopausal Status Are Prognostic Determinants for Triple-Negative Breast Cancer Treated by Neoadjuvant Chemotherapy

BackgroundTriple-negative breast cancers (TNBC) are a specific subtype of breast cancers with a particularly poor prognosis. However, it is a very heterogeneous subgroup in terms of clinical behavior and sensitivity to systemic treatments. Thus, the identification of risk factors specifically associated with those tumors still represents a major challenge. A therapeutic strategy increasingly used for TNBC patients is neoadjuvant chemotherapy (NAC). Only a subset of patients achieves a pathologic complete response (pCR) after NAC and have a better outcome than patients with residual disease.PurposeThe aim of this study is to identify clinical factors associated with the metastatic-free survival in TNBC patients who received NAC.MethodsWe analyzed 326 cT1-3N1-3M0 patients with ductal infiltrating TNBC treated by NAC. The survival analysis was performed using a Cox proportional hazard model to determine clinical features associated with prognosis on the whole TNBC dataset. In addition, we built a recursive partitioning tree in order to identify additional clinical features associated with prognosis in specific subgroups of TNBC patients.ResultsWe identified the lymph node involvement after NAC as the only clinical feature significantly associated with a poor prognosis using a Cox multivariate model (HR = 3.89 [2.42–6.25], p<0.0001). Using our recursive partitioning tree, we were able to distinguish 5 subgroups of TNBC patients with different prognosis. For patients without lymph node involvement after NAC, obesity was significantly associated with a poor prognosis (HR = 2.64 [1.28–5.55]). As for patients with lymph node involvement after NAC, the pre-menopausal status in grade III tumors was associated with poor prognosis (HR = 9.68 [5.71–18.31]).ConclusionThis study demonstrates that axillary lymph node status after NAC is the major prognostic factor for triple-negative breast cancers. Moreover, we identified body mass index and menopausal status as two other promising prognostic factors in this breast cancer subgroup. Using these clinical factors, we were able to classify TNBC patients in 5 subgroups, for which pre-menopausal patients with grade III tumors and lymph node involvement after NAC have the worse prognosis.     

In Situ Identification of CD44+/CD24? Cancer Cells in Primary Human Breast Carcinomas

Breast cancer cells with the CD44+/CD24− phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24− cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24− population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24− cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%–21.23%) of the tumour. A strong correlation was found between the percentage of CD44+/CD24− cells in primary tumours and distant metastasis development (p = 0.0001); in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively). No relationship was evident with tumour size (T) and regional lymph node (N) status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24− cancer cells was an independent factor related to metastasis development (p = 0.004). Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24− tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24− cell percentage.     

YAP蛋白核过表达与卵巢癌腹膜及淋巴结转移的相关性分析

目的:探讨Yes相关蛋白(YAP)与卵巢癌腹膜及淋巴结转移的相关性。方法:选择148例原发性卵巢癌和30例正常卵巢石蜡切片标本,采用Western blot、免疫组化分析YAP蛋白在正常卵巢组织、非转移性卵巢癌组织及转移性卵巢癌组织中的表达,分析YAP蛋白在卵巢癌组织中的表达与临床病理特征的关系,并应用单因素及多因素logistics分析卵巢癌腹膜和淋巴结转移的独立危险因素。结果:YAP蛋白在正常卵巢组织、非转移性卵巢癌组织及转移性卵巢癌组织中的表达量依次增高,两两比较差异均有统计学差异(P0.05)。YAP蛋白核过表达与组织学分化、残余病灶、复发、腹膜转移以及淋巴结转移均显著相关(P0.05)。YAP蛋白核过表达是独立的影响卵巢癌腹膜(OR:5.443;95%CI:2.287-12.950;P0.001)和淋巴结转移(OR:4.477;95%CI:2.059-9.735;P0.001)的独立危险因素。结论:YAP基因核过表达与卵巢癌腹膜转移及淋巴结转移密切相关,有可能作为临床上预测卵巢癌腹膜及淋巴结转移的新的分子标记物。     

SYK expression in human breast cancer

BACKGROUND: Syk (Splenic Tyrosine Kinase) is an intracellular receptor protein kinase involved in cell proliferation, differentiation and phagocytosis. It has been studied in T and B lymphocytes, NK cells and platelets. The strong expression of Syk in mammary gland prompted research into its potential role in mammary carcinogenesis. There have been very few studies about its role in breast cancer with conflicting results. This study aims to investigate the hypothesis that Syk expression is down-regulated in breast cancer compared with ANCT and the association between its expression and clinicopathological parameters. MATERIALS AND METHODS: mRNA was extracted from 48 breast cancer specimens. Relative Syk to ribosomal RNA expression was determined by RT-PCR and Taqman methodology. Mann-Whitney U test was used to examine the association between Syk expression in cancer and ANCT. Spearman's rank correlation test was used to examine the association between Syk expression in tumours and patients' age, tumour size, tumour grade, estrogen and progesterone receptor status, lymph node metastasis, vascular invasion and clinical outcome. RESULTS: The median for the relative value of Syk expression was 0.17 and 0.18 (range: 0.12 - 0.56 and 0.0 - 1.77) for tumours and ANCT respectively. There was no significant association between Syk expression in cancers and ANCT (p= 0.598) nor between Syk expression in tumours and patients' age, tumour size, tumour grade, estrogen and progesterone receptor status, lymph node metastasis, vascular invasion or prognosis. CONCLUSION: This study shows that Syk mRNA expression does not seem to vary between breast tumours and ANCT. Furthermore, we observed no significant association between Syk expression and clinicopathological parameters.