C-C chemokine receptor 4 (CCR4)-positive regulatory T cells interact with tumor-associated macrophages to facilitate metastatic potential after radiation.

PURPOSE: Our previous study revealed that elevated C-C motif chemokine ligand 2 (CCL2) secretion by irradiated cancer cells recruited C-C motif chemokine receptor 2 (CCR2)-positive myeloid cells and polarized M2-type tumor-associated macrophages (TAMs), promoting lung metastasis in an established mouse model. This study investigated the impact of CCL2 and TAMs on adaptive immunity. METHODS: We assessed the influence of CCL2 and TAMs on adaptive immunity through two ectopic allograft mouse models constructed with MB49 bladder cancer cells and Lewis lung carcinoma cells. Both models exhibited delayed primary tumor growth following radiation therapy (RT), but RT promoted the development of pulmonary metastases in C57BL/6 mice. Additionally, we employed a direct coculture system to investigate the interaction between macrophages and target cells in the context of adaptive immunity. RESULTS: C-C motif chemokine receptor 4 (CCR4)-positive regulatory T cells (Tregs) were recruited to the postirradiated tumor microenvironment (TME). Utilizing a CCR4 antagonist to inhibit CCL2-CCR4 activation reversed the infiltration of CCR4 + Tregs and reduced the incidence of pulmonary metastases. In addition, a positive feedback loop between M2-type TAMs and Tregs was observed. The combined blockade of the CCL2-CCR4 and CCL2-CCR2 signaling pathways further decreased the risk of RT-promoted lung metastasis. CONCLUSION: The recruitment of CCR4 + Tregs to the postirradiated TME increases the metastatic potential of tumor cells through increased interactions with M2-type TAMs. A significant reduction in post-RT lung metastases in ectopic mouse models was achieved by disrupting the recruitment of both CCR4 + Tregs and CCR2 + myeloid cells, which are TAM precursors.

Tumor-Derived C-C Motif Ligand 2 Induces the Recruitment and Polarization of Tumor-Associated Macrophages and Increases the Metastatic Potential of Bladder Cancer Cells in the Postirradiated Microenvironment.

PURPOSE: Radiation therapy (RT) is mainly used for bladder preservation in patients with muscle-invasive bladder cancer. The response of urothelial tumors to RT remains unsatisfactory. We investigated the interaction of RT and tumor-associated macrophages (TAMs) in the context of bladder cancer radioresistance. METHODS AND MATERIALS: We evaluated the therapeutic effects of RT and TAM distribution by establishing an ectopic allograft mouse model. A Transwell coculture system was used to simulate the interaction between TAMs and MB49 bladder cancer cells in the tumor microenvironment. Cytokines and chemokines were analyzed in irradiated MB49 cells. Colony formation and Boyden chamber assays were used to assess the cytotoxic effects and the effects of TAMs on MB49 cell invasion, respectively. RESULTS: Local RT delayed primary tumor growth but promoted pulmonary metastases in C57BL/6 mice. Increased secretion of C-C motif chemokine ligand (CCL2) by irradiated MB49 cells, especially in the presence of M1-type TAMs, contributed to the infiltration of bone marrow-derived C-C motif chemokine receptor 2 (CCR2)-positive myeloid cells and the polarization of M1-type TAMs toward the M2 type to promote MB49 cell invasion. Blockade of CCL2-CCR2 activation by a CCR2 antagonist reversed the phenotypic TAM transformation and suppressed pulmonary metastases. CONCLUSIONS: Bladder cancer cells responded to RT by producing CCL2, which recruited TAM precursors from bone marrow and polarized M1-type TAMs toward the M2 type. This phenotypic TAM transformation promoted the pulmonary metastasis of bladder cancer cells after RT. Disrupting the CCL2-CCR2 signaling axis in combination with RT holds promise for improving RT efficacy in bladder cancer.

Acrolein contributes to urothelial carcinomas in patients with chronic kidney disease.

BACKGROUND: Urothelial carcinomas (UCs) are highly prevalent in patients with end-stage renal disease. Chronic kidney disease (CKD) is the predecessor of end-stage renal disease, and it is also associated with UC. However, the interplay between CKD and UC lacks solid evidence. Acrolein is produced by polyamines and has been suggested to be the uremic "toxin." The level of acrolein correlates well with chronic renal failure. We recently found that acrolein-induced DNA damage and inhibited DNA repair in urothelial cells, which contribute to bladder cancer. Therefore, we hypothesize that acrolein is involved in the formation of UC in patients with CKD. MATERIALS AND METHODS: A total of 62 UC patients and 43 healthy control subjects were recruited. Acrolein-DNA (Acr-dG) adducts and p53 gene mutations in UC tissues, plasma acrolein-protein conjugates (Acr-PC) and S-(3-hydroxypropyl)-N-acetylcysteine levels, and urinary Acr metabolites were analyzed in these patients. RESULTS: Acr-dG levels were statistically correlated with CKD stages in UC patients (P < 0.01). Most p53 mutations were G to A and G to T mutations in these patients, and 50% of mutations at G:C pairs occurred in CpG sites, which is similar to the mutational spectra induced by Acr-dG adducts. Acr-PC levels in the plasma of UC patients with CKD were significantly higher than those of control subjects (P < 0.001). Altered urinary S-(3-hydroxypropyl)-N-acetylcysteine was also found in UC patients with CKD compared to control subjects (P < 0.005). CONCLUSION: These results indicate that acrolein acts as an endogenous uremic toxin and contributes to UC formation in patients with CKD.

Nuclear Factor-κB Overexpression is Correlated with Poor Outcomes after Multimodality Bladder-Preserving Therapy in Patients with Muscle-Invasive Bladder Cancer.

The aim of this study was to investigate prognostic molecular targets for selecting patients with muscle-invasive bladder cancer undergoing bladder-preserving therapy. Pretreatment biopsy samples from patients with muscle-invasive bladder cancer receiving trimodality bladder-preserving therapy were analyzed for expression levels of p53, p16, human epidermal growth factor receptor-2 (Her-2), epidermal growth factor receptor (EGFR), nuclear factor-kappa B (NFκB; p65), E-cadherin, matrix metalloproteinase-9 (MMP9), meiotic recombination 11 homolog (MRE11), programmed death-1 ligand (PD-L1), and mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemical (IHC) staining. The correlations between these molecular markers with local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and overall survival (OS) were explored. Biopsy samples from 41 out of 60 patients were evaluated using IHC. Univariate analysis revealed that the high expression of NFκB is associated with significantly worse LPFS, DMFS, and OS, and low expression of p16 is associated with significantly lower LPFS. Upon further multivariate analysis including sex, age, stage, and selected unfavorable factors in the model, NFκB and p16 independently remained significant. The investigational in vitro study demonstrated that irradiation induces up-regulation of NFκB signaling. Irradiated bladder cancer cells showed increased invasion capability and clonogenic survival; inhibition of NFκB signaling by an NFκB inhibitor, SC75741, or RNA interference reversed the observed increases. NFκB expression (p65) is associated with prognostic significance for both LPFS and DMFS in patients treated with bladder-preserving therapy, with consistent impact on cell viability of bladder cancer cells. NFκB may be a putative molecular target to help with outcome stratification.

Biological significance of GATA3, cytokeratin 20, cytokeratin 5/6 and p53 expression in muscle-invasive bladder cancer.

Genetic profiling studies on muscle-invasive bladder cancers (MIBCs) have discovered molecular subtypes with different biological characteristics. Immunohistochemical (IHC) markers such as GATA3, cytokeratin (CK) 20, CK5/6, and p53 are associated with these subtypes. In this study, we investigated the biological and prognostic significance of these IHC markers in MIBCs from 91 patients who underwent radical cystectomy. High Ki-67 indices were associated with negative CK20 (p = 0.002) and diffuse CK5/6 (p = 0.001) staining. By contrast, tumors with diffuse GATA3 expression had low Ki-67 index (p = 0.006). Regarding p53, three staining patterns were associated with a high Ki-67 index: (1) complete absence, (2) diffusely strong nuclear reactivity, and (3) diffusely strong cytoplasmic staining (p < 0.001 compared with other patterns). CK5/6 and CK20 expression was typically present in a reciprocal fashion; however, diffuse GATA3 and CK5/6 coexpression was observed in 13 (14.29%) cases. Among 78 chemotherapy-naïve patients, low GATA3 staining was associated with worse recurrence-free survival in both univariate (p = 0.008) and multivariate analyses (p = 0.002). CK20, CK5/6, or p53 expression was not associated with clinical outcome. Based on our results, IHC staining for GATA3 may help risk stratification in patients with MIBC receiving radical cystectomy. In addition, the differences in Ki-67 indices suggested that aberrant p53 expression was better defined by the three aforementioned patterns, rather than percentage of nuclear staining alone.

Biological significance of TERT promoter mutation in papillary urothelial neoplasm of low malignant potential.

AIMS: Mutations in FGFR3 and the promoter region of the telomerase reverse transcriptase (TERT) gene have been found frequently in urothelial carcinoma of the urinary bladder. However, related data for papillary urothelial neoplasm of low malignant potential (PUNLMP) are limited. In this study, we investigated the mutation status of the TERT promoter, FGFR3 and HRAS in low-grade papillary urothelial neoplasms and evaluated their prognostic significance. METHODS AND RESULTS: The cases included in this study comprised 21 inverted papillomas, 30 PUNLMPs and 34 low-grade non-invasive papillary urothelial carcinomas (NIPUCs). TERT promoter mutations were observed in 10 (33%) PUNLMPs and 17 (50%) low-grade NIPUCs, but not in any inverted papilloma. FGFR3 mutations were observed more frequently in PUNLMP and low-grade NIPUC than in inverted papillomas (P = 0.009), whereas the opposite trend was noted for HRAS mutations (P < 0.001). Regarding the clinical outcome, TERT promoter mutation was associated with a higher recurrence rate in PUNLMP (P = 0.024) but not in low-grade NIPUC (P = 0.530). Notably, PUNLMP cases with TERT promoter mutations had a similar recurrence rate to that in low-grade NIPUC cases (P = 0.487). CONCLUSIONS: Our results suggest that the status of the TERT promoter mutation may serve as a biomarker of prognostic stratification in patients with PUNLMP.

TP53 Mutational Analysis Enhances the Prognostic Accuracy of IHC4 and PAM50 Assays.

IHC4 and PAM50 assays have been shown to provide additional prognostic information for patients with early breast cancer. We evaluated whether incorporating TP53 mutation analysis can further enhance their prognostic accuracy. We examined TP53 mutation and the IHC4 score in tumors of 605 patients diagnosed with stage I-III breast cancer at National Taiwan University Hospital (the NTUH cohort). We obtained information regarding TP53 mutation and PAM50 subtypes in 699 tumors from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort. We found that TP53 mutation was significantly associated with high-risk IHC4 group and with luminal B, HER2-enriched, and basal-like subtypes. Despite the strong associations, TP53 mutation independently predicted shorter relapse-free survival (hazard ratio [HR] = 1.63, P = 0.007) in the NTUH cohort and shorter breast cancer-specific survival (HR = 2.35, P = <0.001) in the METABRIC cohort. TP53 mutational analysis added significant prognostic information in addition to the IHC4 score (∆ LR-χ(2) = 8.61, P = 0.002) in the NTUH cohort and the PAM50 subtypes (∆ LR-χ(2) = 18.9, P = <0.001) in the METABRIC cohort. We conclude that incorporating TP53 mutation analysis can enhance the prognostic accuracy of the IHC4 and PAM50 assays.

Overlap of CD44 expression between prostatic small cell carcinoma and acinar adenocarcinoma.

Small cell carcinoma (SmCC) of the prostate is a rare and aggressive histologic subtype of the prostate cancer. It can sometimes mimic acinar adenocarcinoma with a high Gleason score (GS). A previous study showed that immunohistochemical staining for CD44 could help in the differential diagnosis of these 2 entities. In this study, we used 2 tissue microarrays including 63 cases of prostate cancer (18 pure SmCC, 37 pure acinar adenocarcinoma, and 8 mixed acinar adenocarcinoma and SmCC) to validate the value of CD44. When analyzed as a continuous variable, CD44 positivity was significantly higher in acinar adenocarcinoma with GS 8 than GS 9 to 10 (P = .027). However, the difference of CD44 expression between SmCC and acinar adenocarcinoma was insignificant. The current study fails to confirm the value of CD44 in differential diagnosis between prostatic SmCC and acinar adenocarcinoma.

Rosai-Dorfman disease of the genito-urinary tract: analysis of six cases from the testis and kidney.

AIMS: Rosai-Dorfman disease (RDD) commonly occurs in lymph nodes, but it can also affect the genitourinary (GU) system. In a search of GU RDD, we identified three cases involving the testis and three the kidney. METHODS AND RESULTS: The mean age was 52.4 (35-76) years. Tumour sizes were 3.6 cm on average (1.5-4.3) for testicular cases and 15.5 cm for the renal case treated by nephrectomy. All renal cases showed typical morphology similar to nodal RDD with scattered foci of lymphocytic aggregation. In contrast, all three testicular cases had an evenly distributed lymphocyte and plasma cell infiltration with entrapment of Sertoli-only seminiferous tubules. In all six cases, immunohistochemistry (IHC) for S100 showed strong reactivity in the lesional histiocytes and highlighted the hallmark emperipolesis. One testicular case had pleural and pericardial effusions but resolved after removal of the RDD lesion. Another renal case subsequently involved bone and then lung over a 3-year period. CONCLUSIONS: RDD involving the GU system is rare with it most commonly involving the kidney followed by testis. Our three renal cases were similar in morphology to typical nodal RDD. The testicular cases had a somewhat different histological picture and needed IHC for S100 to verify the diagnosis.

Value of transition zone biopsy in active surveillance of prostate cancer.

PURPOSE: For patients on active surveillance there are limited data on transition zone sampling upon followup biopsy. We verified the value of transition zone biopsy in the active surveillance setting. MATERIALS AND METHODS: Our study included 1,059 sets of prostate biopsies from a total of 534 patients on active surveillance at the Johns Hopkins Hospital. Each set comprised at least 14 cores with 2 or more from the transition zone. Of these men 53 underwent radical prostatectomy. RESULTS: Patients with tumors in the peripheral zone as well as the transition zone had a higher maximum Gleason score and an increased maximum percent of cancer per core than men with tumor in the peripheral or transition zone only. In 12 of the 534 patients (2.2%) the tumor on active surveillance biopsy was limited to transition zone core(s). Of the 534 patients 11 (2.1%) had tumor with a high Gleason score (greater than 6) or extensive involvement (greater than 50%) of any core exclusively on transition zone biopsy. However, in 10 of 15 radical prostatectomy cases (66.7%) with prior positive transition zone biopsies the tumors had little or no transition zone component. In addition, transition zone status on biopsy had no significant relationship with Gleason score, extraprostatic extension or seminal vesicle involvement at radical prostatectomy. CONCLUSIONS: Our data suggest that the additional yield is sufficiently low to argue against routine transition zone sampling in men undergoing followup biopsy on active surveillance. However, further study is needed to make definitive recommendations.

Clear cell carcinoma of female urethral diverticulum--a case report.

Primary malignancies of female urethral diverticulum are rare. A well-documented female patient with primary clear cell carcinoma of the urethral diverticulum is presented here. A 65-year-old woman presented with frequency and voiding difficulty for 2 months. Physical examination showed a 4-cm mass protruding from anterior vaginal wall. Intravenous urography, magnetic resonance imaging, and cystoscopy showed a polypoid mass in urethral diverticulum. She then underwent anterior exenteration with ileal conduit diversion and urethrectomy. Pathology confirmed the diagnosis of clear cell adenocarcinoma with bladder neck invasion. She had no disease recurrence at 2-year follow-up. Careful clinical examination and image studies are helpful in making the preoperative diagnosis for the rare disease. Early radical surgery can achieve better survival.

Differential expression of ubiquitin carboxy-terminal hydrolase L1 in breast carcinoma and its biological significance.

Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that hydrolyzes ubiquitin. Previous reports have shown both tumorigenic and antitumorigenic roles for UCHL1. However, the expression patterns of UCHL1 protein, an area that is critical for validating its clinicopathologic roles among subtypes of breast cancer, is still lacking. Here we examined the expression of UCHL1 by immunohistochemistry in 243 breast carcinomas of various subtypes. We found expression of UCHL1 in 8.3% of invasive ductal carcinomas but not in other carcinoma subtypes, except for metaplastic carcinomas of the breast, which showed UCHL1 staining in 61.9% of cases, with the sarcomatous components being more intensely stained. UCHL1 expression in invasive ductal carcinomas significantly correlated with a high histologic grade (P = .001), the triple-negative phenotype (P = .02), and the basal-like phenotype (P <.001); furthermore, it was associated with poorer overall survival by univariate and multivariate analyses. Knockdown of UCHL1 in an invasive Snail variant-transfected MCF7 cells with high endogenous UCHL1 protein level significantly reduced invasion and anchorage-independent growth. Conclusively, our results demonstrate a role for UCHL1 in aggressive phenotypes in breast carcinoma. The high expression of UCHL1 in metaplastic carcinomas of the breast, which is pathogenically related to epithelial-mesenchymal transition, may implicate an association between UCHL1 expression and the epithelial-mesenchymal transition in breast cancer.

Ubiquitin carboxy-terminal hydrolase L1 may be involved in the development of mammary phyllodes tumors.

Phyllodes tumors (PTs) are characterized by co-proliferation of the stroma and epithelium, with the stroma being the neoplastic element. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that was originally considered to be a neuronal-specific marker, but later reports have shown both tumorigenic and antitumorigenic roles for UCHL1. Although a role for UCHL1 has been explored in many cancers, a study on PTs has never been reported. We assessed UCHL1 expression in 49 cases of PTs and 16 fibroadenomas using immunohistochemistry and examined associations with clinicopathological features. In normal breast, strong staining for UCHL1 was consistently observed in the nerve bundles, if present, in breast stroma. Scattered stromal cells showed negative to weak staining. The ductal and lobular units, in contrast, showed no staining. In contrast to the 16 fibroadenomas, of which only 3 showed mild staining, UCHL1 expression was consistently observed in all 49 PTs. There was a significantly increasing trend of UCHL1 expression with increasing PT grade (P < 0.001); strong staining was observed in 24 % of benign PTs, but was present in 56 and 90 % of borderline and malignant PTs, respectively. Consistently, UCHL1 was focally positive in regions of benign to borderline malignancy, but strongly and diffusely immunoreactive in regions of malignancy in cases of malignant PTs. In addition to PT grade, UCHL1 expression correlated with increasing stromal atypia (P = 0.01), but not with other clinicopathological parameters. In conclusion, the consistent expression of UCHL1 in PTs and an increasing trend of UCHL1 expression with an increasing PT grade suggest a role for UCHL1 in the pathogenesis and malignant progression of PTs.

Clinical significance of ESR1 gene copy number changes in breast cancer as measured by fluorescence in situ hybridisation.

AIMS: The ESR1 gene encodes for oestrogen receptor (ER) α, which plays a crucial role in mammary carcinogenesis and clinical outcome in patients with breast cancer. However, the clinical significance of the ESR1 gene copy number change for breast cancer has not been clarified. METHODS: ESR1 gene copy number was determined by fluorescence in situ hybridisation (FISH) on tissue sections. A minimum of 20 tumour cells were counted per section, and a FISH ratio of ESR1 gene to CEP6 ≥ 2.0 was considered ESR1 amplification. A ratio >1.2 but <2.0 was considered ESR1 gain. The ESR1 copy number was further measured by quantitative real-time PCR (Q-PCR) with ASXL2 as a reference. RESULTS: FISH revealed ESR1 amplification in six cases (4.0%) and ESR1 gain in 13 cases (8.7%) from a total of 150 cases. ESR1 gain and amplification were more common in older patients (p<0.001), and correlated well with ER protein expression (p=0.03) measured by immunohistochemistry, and ESR1 copy number (p<0.001) measured by Q-PCR. Furthermore, the multivariate analysis revealed that ESR1 amplification was associated with a shorter disease-free survival (HR=5.56, p=0.03) and a shorter overall survival (HR=5.11, p=0.04). CONCLUSIONS: In general, the frequency of ESR1 amplification in breast cancer is low when measured by FISH in large sections. ESR1 gain and amplification in breast cancer may be associated with older age and poorer outcomes.

Underexpression of hepatocyte nuclear factor-1ß in chromophobe renal cell carcinoma.

AIMS: Chromophobe renal cell carcinoma (ChRCC) is an uncommon malignant renal neoplasm with a generally indolent clinical behaviour. Previous studies revealed biallelic inactivation of the hepatocyte nuclear factor-1ß (HNF1ß) gene in several patients with ChRCC. The aims of this study were to determine HNF1ß expression in renal neoplasms and the potential of HNF1ß as a diagnostic marker for ChRCC. METHODS AND RESULTS: We performed immunohistochemical staining of 79 samples taken from patients with primary renal neoplasm [19 renal oncocytomas, 18 ChRCCs, 24 clear cell renal cell carcinomas (CCRCCs), and 18 papillary renal cell carcinomas]. HNF1ß was underexpressed in 16 of 18 cases of ChRCC (88.9%). By contrast, HNF1ß expression was preserved in the majority of renal oncocytoma (94.7%, 18/19) and CCRCC (95.8%, 23/24) cases. The combined use of HNF1ß and cytokeratin 7 (CK7) further increased the diagnostic sensitivity and specificity; the profile of HNF1ß positivity and CK7 negativity was not visible in any ChRCC sample, but was common in both renal oncocytoma (94.7%, 18/19) and CCRCC (91.7%, 22/24) samples. CONCLUSIONS: The results suggest that a lack of HNF1ß expression might play an important role in the pathogenesis of ChRCC, and may serve as a good diagnostic marker for this neoplasm.

Primary gastric synovial sarcoma.

Synovial sarcoma is a malignant soft tissue neoplasm that may arise from a variety of sites in the human body. It is typically characterized by its biphasic histological pattern, but a monophasic type composed entirely of spindle cells also exists. The diagnosis of monophasic synovial sarcoma can be very challenging and often requires molecular diagnostic techniques, especially for tumors arising in rare locations such as the gastrointestinal tract. We report here the case of a 38-year-old woman with a primary gastric monophasic synovial sarcoma confirmed by reverse transcriptase polymerase chain reaction that revealed t(X;18) (SYT-SSX1) translocation. To our knowledge, only 11 synovial sarcomas arising in the stomach have previously been reported. The pathologic features, differential diagnoses, and clinical manifestations are discussed.

Aqueous Extract of Paeonia suffruticosa Inhibits Migration and Metastasis of Renal Cell Carcinoma Cells via Suppressing VEGFR-3 Pathway.

Renal cell carcinoma (RCC) cells are characterized by strong drug resistance and high metastatic incidence. In this study, the effects of ten kinds of Chinese herbs on RCC cell migration and proliferation were examined. Aqueous extract of Paeonia suffruticosa (PS-A) exerted strong inhibitory effects on cancer cell migration, mobility, and invasion. The results of mouse xenograft experiments showed that the treatment of PS-A significantly suppressed tumor growth and pulmonary metastasis. We further found that PS-A markedly decreased expression of VEGF receptor-3 (VEGFR-3) and phosphorylation of FAK in RCC cells. Moreover, the activation of Rac-1, a modulator of cytoskeletal dynamics, was remarkably reduced by PS-A. Additionally, PS-A suppressed polymerization of actin filament as demonstrated by confocal microscopy analysis and decreased the ratio of F-actin to G-actin in RCC cells, suggesting that PS-A inhibits RCC cell migration through modulating VEGFR-3/FAK/Rac-1 pathway to disrupt actin filament polymerization. In conclusion, this research elucidates the effects and molecular mechanism for antimigration of PS-A on RCC cells and suggests PS-A to be a therapeutic or adjuvant strategy for the patients with aggressive RCC.

Differential expression of moesin in breast cancers and its implication in epithelial-mesenchymal transition.

AIMS: Moesin belongs to the ERM (ezrin, radixin and moesin) family. Recent in-vitro studies have shown the possible involvement of moesin in epithelial-mesenchymal transition (EMT), but correlating in-vivo evidence is lacking. METHODS AND RESULTS: To study the biological significance of moesin, we used immunohistochemistry to investigate the in-situ expression profiles of moesin in 322 breast carcinomas of different subtypes, including 23 cases of metaplastic carcinoma (MCB) which is pathogenetically considered to involve EMT. Moesin was highly expressed in 95.7% of cases of MCB, and in 16% of cases of invasive ductal carcinoma (IDC), but was negative in all other subtypes of breast carcinomas. In IDCs, moesin expression correlated positively with a high histological grade (P < 0.001), basal-like phenotype (P < 0.001) and poor overall survival (P = 0.0263). Transfection of MCF7 cells with Snail, one of the key regulators of EMT, showed up-regulation of moesin at the transcriptional level. Finally, mRNA level of moesin correlated positively with Snail and EMT-related genes in a microarray data set using primary breast cancer samples. CONCLUSION: These results offer biological evidence of moesin as an EMT marker, support the association between moesin, Snail and EMT and suggest a role for moesin in breast cancer prognostication.