YWHAZ and TBP are potential reference gene candidates for qPCR analysis of response to radiation therapy in colorectal cancer.

The expression profiles of conventional reference genes (RGs), including ACTB and GAPDH, used in quantitative real-time PCR (qPCR), vary depending on tissue types and environmental conditions. We searched for suitable RGs for qPCR to determine the response to radiotherapy in colorectal cancer (CRC) cell lines, organoids, and patient-derived tissues. Ten CRC cell lines (Caco-2, COLO 205, DLD-1, HCT116, HCT-15, HT-29, RKO, SW1116, SW480, and SW620) and organoids were selected and irradiated with 2, 10 or 21 grays (Gy) based on the previous related studies conducted over the last decade. The expression stability of 14 housekeeping genes (HKGs; ACTB, B2M, G6PD, GAPDH, GUSB, HMBS, HPRT1, IPO8, PGK1, PPIA, TBP, TFRC, UBC, and YWHAZ) after irradiation was evaluated using RefFinder using raw quantification cycle (Cq) values obtained from samples before and after irradiation. The expression stability of HKGs were also evaluated for paired fresh frozen tissues or formalin-fixed, paraffin-embedded samples obtained from CRC patients before and after chemoradiotherapy. The expression of YWHAZ and TBP encoding 14-3-3-zeta protein and TATA-binding protein were more stable than the other 12 HKGs in CRC cell lines, organoids, and patient-derived tissues after irradiation. The findings suggest that YWHAZ and TBP are potential RG candidates for normalizing qPCR results in CRC radiotherapy experiments.

RPL27 contributes to colorectal cancer proliferation and stemness via PLK1 signaling.

Although expression of ribosomal protein L27 (RPL27) is upregulated in clinical colorectal cancer (CRC) tissue, to the best of our knowledge, the oncogenic role of RPL27 has not yet been defined. The present study aimed to investigate whether targeting RPL27 could alter CRC progression and determine whether RPL27 gains an extra­ribosomal function during CRC development. Human CRC cell lines HCT116 and HT29 were transfected with RPL27­specific small interfering RNA and proliferation was assessed in vitro and in vivo using proliferation assays, fluorescence­activated cell sorting (FACS) and a xenograft mouse model. Furthermore, RNA sequencing, bioinformatic analysis and western blotting were conducted to explore the underlying mechanisms responsible for RPL27 silencing­induced CRC phenotypical changes. Inhibiting RPL27 expression suppressed CRC cell proliferation and cell cycle progression and induced apoptotic cell death. Targeting RPL27 significantly inhibited growth of human CRC xenografts in nude mice. Notably, polo­like kinase 1 (PLK1), which serves an important role in mitotic cell cycle progression and stemness, was downregulated in both HCT116 and HT29 cells following RPL27 silencing. RPL27 silencing reduced the levels of PLK1 protein and G2/M­associated regulators such as phosphorylated cell division cycle 25C, CDK1 and cyclin B1. Silencing of RPL27 reduced the migration and invasion abilities and sphere­forming capacity of the parental CRC cell population. In terms of phenotypical changes in cancer stem cells (CSCs), RPL27 silencing suppressed the sphere­forming capacity of the isolated CD133+ CSC population, which was accompanied by decreased CD133 and PLK1 levels. Taken together, these findings indicated that RPL27 contributed to the promotion of CRC proliferation and stemness via PLK1 signaling and RPL27 may be a useful target in a next­generation therapeutic strategy for both primary CRC treatment and metastasis prevention.

Unexpected hyperechoic lesions of the breast and their correlations with pathology: a pictorial essay.

Hyperechoic lesions of the breast encompass a wide range of conditions that are occasionally encountered during breast ultrasonography. Although typical hyperechoic lesions with a distinct fat component on imaging are well known, some hyperechoic lesions are diagnosed as unexpected pathology, making the radiology-pathology correlation difficult. Therefore, understanding the pathology of these lesions and how it correlates with imaging findings can help radiologists accurately diagnose and properly manage a range of related conditions. This article presents a pictorial review of unexpected hyperechoic benign and malignant breast lesions, with a focus on the pathological conditions that give rise to the hyperechoic pattern.

High-throughput SNP markers for authentication of Korean wheat cultivars based on seven complete plastomes and the nuclear genome.

Wheat (Triticum aestivum) has diverse uses in the food industry, and different cultivars have unique properties; therefore, it is important to select the optimal cultivar for the intended end use. Here, to establish an identification system for Korean wheat cultivars, we obtained the complete plastome sequences of seven major Korean cultivars. Additionally, the open access database CerealsDB was queried to discover single-copy genomic single-nucleotide polymorphisms (SNPs) in the hexaploid wheat genome. Ten SNPs were developed into allele-specific PCR (ASP) markers, and eight of the SNPs used for ASP markers were converted into TaqMan high-throughput genotyping markers. Phylogenetic analysis using SNP genotypes revealed the genetic diversity and relationships among 137 wheat lines from around the world, including 35 Korean cultivars. This research thus presents a high-throughput authentication system for Korean wheat cultivars that may promote food industry uses of Korean wheat. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01043-w.

Evaluation of a Direct Reverse Transcription Loop-Mediated Isothermal Amplification Method without RNA Extraction (Direct RT-LAMP) for the Detection of Lymph Node Metastasis in Early Breast Cancer.

PURPOSE: Assessing lymph node metastasis, tumor-derived DNA, or tumor-derived RNA has previously been studied in place of immunohistochemical assay. Because a direct reverse transcription loop-mediated isothermal amplification method (direct RT-LAMP) has been previously developed in order to rapidly identify viruses in place of RNA extraction, our team hypothesized that a direct RT-LAMP assay can be employed as a substitute in order to detect tumor involvement of lymph nodes within breast cancer patients. MATERIALS AND METHODS: A total amount of 92 lymph nodes removed across 40 patients possessing breast cancer were collected at Kyungpook National University Chilgok Hospital between the months of November 2015 and February 2016. All samples were then evaluated and contrasted via both a direct RT-LAMP assay and routine histopathologic examination. RESULTS: The sensitivity and specificity of the direct RT-LAMP assay were 85.7% and 100%, respectively. The positive predictive value and negative predictive value were 100% and 94.4%, respectively. CONCLUSION: Direct RT-LAMP assay is capable of facilitating the detection of sentinel lymph node metastasis within breast cancer patients intraoperatively possessing an excellent sensitivity via a cost-effective and time-saving manner.

Ssu72-HNF4α signaling axis classify the transition from steatohepatitis to hepatocellular carcinoma.

Growing evidence suggests a mechanistic link between steatohepatitis and hepatocellular carcinoma (HCC). However, the lack of representative animal models hampers efforts to understand pathophysiological mechanisms underlying steatohepatitis-related HCC. We found that liver-specific deletion of Ssu72 phosphatase in mice, leads to a high incidence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, but not HCC. However, loss of Ssu72 drastically increased the probability of HCC developing, as well as the population of hepatic progenitors, in various chemical and metabolic syndrome-induced HCC models. Importantly, hepatic Ssu72 loss resulted in the induction of mature hepatocyte-to-progenitor cell conversion, by dedifferentiation orchestrated by Ssu72-mediated hypo-phosphorylation of hepatocyte nuclear factor 4α (HNF4α), a master regulator of hepatocyte function. Our findings suggest that Ssu72-mediated HNF4α transcription contributes to the progression of steatohepatitis-associated HCC by regulating the dedifferentiation potential of hepatocytes. Thus, targeting the Ssu72-mediated HNF4α signaling that underlies the pathogenesis of steatohepatitis-associated HCC development could be a novel therapeutic intervention for steatohepatitis-associated HCC.

Value of accurate diagnosis for metastatic supraclavicular lymph nodes in breast cancer: assessment with neck US, CT, and 18F-FDG PET/CT.

PURPOSE: Neck ultrasonography (US), computed tomography (CT), and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) are all known to be useful imaging modalities for detecting supraclavicular lymph node (SCN) metastasis in breast cancer. The authors compared the diagnostic values of neck US, CT, and PET/CT in the detection of SCN metastasis in breast cancer. METHODS: SCN metastases identified in neck US, CT, or PET/CT during follow-up visits of patients with breast cancer were pathologically confirmed with the use of US-guided fine-needle aspiration cytology. The clinicopathological factors of the patients were analyzed, and the statistical parameters including sensitivity, specificity, positive and negative predictive values, false-positive and false-negative rates, and accuracy of neck US, CT, and PET/CT were compared. RESULTS: Among 32 cases of suspicious SCNs, 24 were pathologically confirmed as metastasis of breast cancer. The sensitivity of US + CT was 91.7%, which was the same as that of PET/CT, while the sensitivity rates of US alone and CT alone were 87.5% and 83.3%, respectively. Accuracy was 99.8% in PET/CT alone and 98.1% in US + CT. The false-negative rate was 0.1% in US + PET/CT, while it was 0.2% in PET/CT and US + CT, 0.3% in US alone and 0.4% in CT alone. CONCLUSION: PET/CT can be the first choice for detecting SCN metastases in breast cancer. However, if PET/CT is unavailable for any reason, US + CT could be a good second option to avoid false-negative results.

Neo-Fs Index: A Novel Immunohistochemical Biomarker Panel Predicts Survival and Response to Anti-Angiogenetic Agents in Clear Cell Renal Cell Carcinoma.

Background: Frameshift indels have emerged as a predictor of immunotherapy response but were not evaluated yet to predict anti-angiogenetic agent (AAA) response or prognosis in clear cell renal cell carcinoma (ccRCC). Methods: Here, to develop biomarkers that predict survival and response to AAA, we evaluated the immunohistochemical expression of proteins whose genes frequently harbor frameshift indels in 638 ccRCC patients and correlated the individual and integrated markers with prognosis and AAA response. The mutational landscape was evaluated using targeted next-generation sequencing in 12 patients concerning protein markers. Immune gene signatures were retrieved from TCGA RNA seq data. Results: Five proteins (APC, NOTCH1, ARID1A, EYS, and filamin A) were independent adverse prognosticators and were incorporated into the Neo-fs index. Better overall, disease-specific and recurrence-free survival were observed with high Neo-fs index in univariate and multivariate survival analyses. Better AAA responses were observed with a high Neo-fs index, which reflected increased MHC class I, CD8+ T cell, cytolytic activity, and plasmacytoid dendritic cell signatures and decreased type II-IFN response signatures, as well as greater single-nucleotide variant (SNV) and indel counts. Conclusions: Neo-fs index, reflecting antitumor immune signature and more SNVs. and indels, is a powerful predictor of survival and AAA response in ccRCC.

Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer.

BACKGROUND: Neoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC. METHODS: We analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets. RESULTS: Gene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature. CONCLUSIONS: Taken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.

Standardized Pathology Report for Breast Cancer.

Given the recent advances in management and understanding of breast cancer, a standardized pathology report reflecting these changes is critical. To meet this need, the Breast Pathology Study Group of the Korean Society of Pathologists has developed a standardized pathology reporting format for breast cancer, consisting of 'standard data elements,' 'conditional data elements,' and a biomarker report form. The 'standard data elements' consist of the basic pathologic features used for prognostication, while other factors related to prognosis or diagnosis are described in the 'conditional data elements.' In addition to standard data elements, all recommended issues are also presented. We expect that this standardized pathology report for breast cancer will improve diagnostic concordance and communication between pathologists and clinicians, as well as between pathologists inter-institutionally.

Standardized pathology report for breast cancer.

Given the recent advances in management and understanding of breast cancer, a standardized pathology report reflecting these changes is critical. To meet this need, the Breast Pathology Study Group of the Korean Society of Pathologists has developed a standardized pathology reporting format for breast cancer, consisting of 'standard data elements,' 'conditional data elements,' and a biomarker report form. The 'standard data elements' consist of the basic pathologic features used for prognostication, while other factors related to prognosis or diagnosis are described in the 'conditional data elements.' In addition to standard data elements, all recommended issues are also presented. We expect that this standardized pathology report for breast cancer will improve diagnostic concordance and communication between pathologists and clinicians, as well as between pathologists inter-institutionally.

The Therapeutic Effect of Cyclin-Dependent Kinase 4/6 Inhibitor on Relapsed Ectopic Male Breast Cancer.

Ectopic male breast cancer is very rare. Consequently, there is a lack of prospective clinical trials, and most recommendations for treatment are based on the experiences of clinicians and data from female breast cancer patients. The United States Food and Drug Administration has recently approved palbociclib combined with endocrine therapy for advanced male breast cancer because of the positive results of its use in metastatic female breast cancer. Therefore, it is worth considering cyclin-dependent kinase 4/6 inhibitors as alternatives to conventional chemotherapies for advanced male breast cancer patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative cancers. The present case report introduces the use of palbociclib plus letrozole as first-line therapy for an elderly male patient with relapsed ectopic breast cancer, notwithstanding the limitations of the current national health insurance policy.

Tumor budding in cervical cancer as a prognostic factor and its possible role as an additional intermediate-risk factor.

OBJECTIVE: To evaluate the prognostic value and its possible role as an additional intermediate-risk factor of tumor budding (TB) in cervical cancer following radical hysterectomy. METHODS: In total, 136 patients with cervical cancer who underwent radical hysterectomy with pelvic and/or paraaortic lymphadenectomy were included. We assessed the status of TB in available hematoxylin and eosin-stained specimens. Univariate and multivariate analyses for predicting tumor recurrence and death were performed using TB and other clinicopathologic parameters. To evaluate additional intermediate-risk factors of TB, patients who had at least one high-risk factor were excluded, and a total of 81 patients were included. We added TB to three conventional intermediate-risk models and compared their performance with new and conventional models using the log-rank test and receiver operating characteristic analysis. RESULTS: High TB was defined as ≥5 per high-power field for disease-free survival and ≥ 8 per high-power field for overall survival. Multivariate analysis revealed that high TB was an independent prognostic factor for predicting overall survival (hazard ratio, 4.96; 95% confidence intervals, 1.06-23.29; p = .0423). The addition of TB to the conventional intermediate-risk models improved the accuracy of recurrence prediction. Among the risk models, the new model using at least two risk factors, including tumor size (≥ 4 cm), deep stromal invasion (outer one-third of entire cervical thickness), lymphovascular invasion, and high TB, was the most accurate for predicting tumor recurrence (area under the curve, 0.708, hazard ratio, 4.25; p = .0231). CONCLUSION: High TB may be a prognostic biomarker of cervical cancer. Moreover, the addition of TB to the conventional intermediate-risk models improves the stratification of tumor recurrence.

CytoPAN-Portable cellular analyses for rapid point-of-care cancer diagnosis.

Rapid, automated, point-of-care cellular diagnosis of cancer remains difficult in remote settings due to lack of specialists and medical infrastructure. To address the need for same-day diagnosis, we developed an automated image cytometry system (CytoPAN) that allows rapid breast cancer diagnosis of scant cellular specimens obtained by fine needle aspiration (FNA) of palpable mass lesions. The system is devoid of moving parts for stable operations, harnesses optimized antibody kits for multiplexed analysis, and offers a user-friendly interface with automated analysis for rapid diagnoses. Through extensive optimization and validation using cell lines and mouse models, we established breast cancer diagnosis and receptor subtyping in 1 hour using as few as 50 harvested cells. In a prospective patient cohort study (n = 68), we showed that the diagnostic accuracy was 100% for cancer detection and the receptor subtyping accuracy was 96% for human epidermal growth factor receptor 2 and 93% for hormonal receptors (ER/PR), two key biomarkers associated with breast cancer. A combination of FNA and CytoPAN offers faster, less invasive cancer diagnoses than the current standard (core biopsy and histopathology). This approach should enable the ability to more rapidly diagnose breast cancer in global and remote settings.

FGFR1 is associated with c-MYC and proangiogenic molecules in metastatic renal cell carcinoma under anti-angiogenic therapy.

AIMS: This study aimed to investigate the clinicopathological significance of FGFR1 and c-MYC expression, particularly in relation to angiogenesis in clear cell renal cell carcinoma (CCRCC). METHODS AND RESULTS: Immunohistochemistry and fluorescence in-situ hybridisation were conducted with tissue microarrays from 91 metastatic CCRCC patients who received VEGF receptor tyrosine kinase inhibitors (VEGFR-TKIs). The expression of angiogenic molecules, FGFR1 and c-MYC, and tumoral vascular density (TVD) and mRNA expression and TVD of 533 CCRCCs in The Cancer Genome Atlas (TCGA) were analysed. FGFR1, pFGFR1 and c-MYC expression was observed in 29.1, 74.4 and 30.8% of tumours, respectively. FGFR1high was an independent worse prognostic factor for overall (HR = 1.871, P = 0.032) and progression-free (HR = 1.976, P = 0.016) survival. FGFR1high was significantly related to VEGFR-TKI responsiveness (P = 0.011). The presence of FGFR1high /c-MYChigh showed a positive correlation with proangiogenic markers, including VEGF (P = 0.018) and HIF-1α (P < 0.0001). FGFR1high /c-MYChigh tumours showed higher TVDs together with higher VEGFR2 and PDGFR-ß expression (both P < 0.0001). FGFR1 and c-MYC expression was also positively correlated with the expression of hypoxia-related and proangiogenic-related genes in the TCGA data. CONCLUSIONS: FGFR1 and c-MYC may be involved in tumour angiogenesis and FGFR1 may represent a promising therapeutic target in metastatic CCRCC.

Comparison of clinical features and oncologic outcomes between familial non-hereditary and hereditary breast cancer in Korean female patients.

BACKGROUND: The authors compared the clinical features between familial (non-hereditary) and hereditary breast cancer. And we also analyzed their oncologic outcomes to establish appropriate surveillance protocol for familial (non-hereditary) and hereditary breast cancer. METHODS: Among 232 patients with breast cancer who were performed BRCA gene evaluation, twenty-eight patients were diagnosed as hereditary breast cancer with BRCA gene mutation and one-hundred and seventy-six patients were familial (non-hereditary) breast cancer. The clinical characteristics and oncologic outcomes were compared between two groups. RESULTS: While the incidence of multifocality was higher in familial (non-hereditary) breast cancer group (p < 0.001), the bilaterality was higher in hereditary breast cancer group (p < 0.001). And the rate of pathologic complete remission was also significantly higher in hereditary breast cancer group (p = 0.030). The characteristics of tumor were different between familial (non-hereditary) breast cancer and hereditary breast cancer. The oncologic outcome was better in familial (non-hereditary) breast cancer group than hereditary breast cancer group except death. CONCLUSION: The clinical characteristics of familial (non-hereditary) breast cancer were different from those of hereditary breast cancer but similar to those of sporadic breast cancer. The prognosis of the familial (non-hereditary) breast cancer was significantly better than hereditary breast cancer.

Absence of estrogen receptor is associated with worse oncologic outcome in patients who were received neoadjuvant chemotherapy for breast cancer.

BACKGROUND/OBJECTIVE: Neoadjuvant chemotherapy (NAC) is a standard treatment for locally advanced breast cancer, especially for HER2-positive or triple negative breast cancer which shows good response to chemotherapy. However, because a result of biomarkers is, occasionally, changed after NAC, the treatment strategy should be differently applied for patients with locally advanced breast cancer. We compared the results of biomarkers before and after NAC to evaluate the association with disease prognosis and oncologic results. METHODS: Fifty-seven patients with locally advanced breast cancer underwent NAC and the immunohistochemical (IHC) staining results were compared between before and after NAC. And the association between oncologic outcomes and biomarkers was analyzed. RESULTS: Negative status of estrogen receptor (ER) was associated with locoregional recurrence and distant metastasis both before and after NAC (p = 0.021, 0.019; p = 0.018, 0.036). And the negative status of progesterone receptor (PR) and triple negative status before neoadjuvant chemotherapy were also associated with death and distant metastasis, respectively. However, the changes of biomarkers after NAC in breast cancer were not directly associated with any oncologic outcomes. CONCLUSION: The absence of ER in breast cancer before and after NAC would be a significant prognostic factor for local recurrence and distant metastasis. Therefore, the absence of ER should be considered as important factor in determining the treatment strategy.

A rare pericytic tumor of the kidney: The first case in Korea.

INTRODUCTION: A pericytic tumor is a group of mesenchymal neoplasm found in superficial tissues and only rarely described in viscera. The family of pericytic tumors includes glomus tumors and variants, myopericytoma including myofibroma, and angioleiomyoma etc. The renal pericytic tumor is extremely rare, and only few comprehensive discussions about this entity have been done. PRESENTATION OF CASE: A 58-year-old man was transferred to our institute with suspicions of renal cell carcinoma. The kidney dynamic computed tomography scan showed a 3 cm sized solid mass in the upper pole of the right kidney. Laparoscopic radical nephrectomy was performed due to the deep-seated mass. Pathological result confirmed that the kidney mass was renal pericytic tumor. DISCUSSION: Although general biological behavior of published renal pericytic tumors is likely to be benign, the clinicopathologic experiences are very limited. Therefore, we should evaluate the malignant potential of the entity according to the parameters proposed for soft tissue tumors, including tumor location, tumor size, growth pattern, cellularity, cytological atypia, and mitotic figures with atypical forms. The current case shows several worrisome features, including an extremely rare tumor location, partially infiltrative growth, and a mildly increased proliferating index, which resulted in it being classified as an uncertain malignant potential. CONCLUSION: We described the first case of renal pericytic tumor, addressing uncertain malignant potential, in a Korean male, which would be a distinct mesenchymal neoplasm differentiating from other groups of perivascular tumor families based on histological and immunohistochemical features.

Clinical Validation of BCT Scores With Prognostic Factors in Hormone Receptor-positive, HER2-negative Early Breast Cancer.

BACKGROUND/AIM: Multigene profiling assays provide strong evidence for predicting the prognosis of breast cancer. In this study, we aimed to evaluate the clinical validation of the BCT score with various prognostic factors. MATERIALS AND METHODS: A total of 133 cases of hormone receptor-positive, cT1N0 breast cancers were analyzed. Risk stratification using the BCT score (Low, n=105; High, n=28) was analyzed with Ki67 index, p53 mutation, Immunohistochemistry 4 (IHC4) score, Nottingham Prognostic Index (NPI) and online PREDICT. RESULTS: Ki67 index and NPI showed strong correlations with risk stratification based on BCT scores. Although the IHC4 score and online PREDICT were not associated with BCT score, there was a significant tendency of association with the online PREDICT results as the time of overall survival was increasing. CONCLUSION: Risk classification based on BCT scores might have a clinical significance as a prognostic marker in hormone receptor-positive, HER2-negative, early breast cancer.

Overcoming Tamoxifen Resistance by Regulation of Del-1 in Breast Cancer.

BACKGROUND: Hormone receptor-positive breast cancer accounts for nearly two-thirds of breast cancer cases; it ultimately acquires resistance during endocrine treatment and becomes more aggressive. This study evaluated the role of developmental endothelial locus (Del)-1 in tamoxifen-resistant (TAM-R) breast cancer. METHODS: Del-1 expression in recurrent TAM-R breast cancer tissue was evaluated and compared to that in the original tumor tissue from the same patients. Del-1 expression was also evaluated in TAM-R cells by quantitative real-time PCR, western blotting, and enzyme-linked immunosorbent assay. The effects of Del-1 knockdown on the proliferation, migration, and invasion of TAM-R cells was assessed with wound-healing and Matrigel transwell assays. RESULTS: Del-1 was more highly expressed in recurrent breast cancer as compared to the original tumor tissues before initiation of endocrine treatment. Del-1 mRNA was upregulated in TAM-R and small interfering RNA-mediated knockdown of Del-1 suppressed the migration and proliferation of TAM-R cells while partly restoring TAM sensitivity. And the TAM resistance was recovered by knockdown of Del-1. CONCLUSIONS: TAM-R breast cancer is characterized by Del-1 overexpression and tumor progression can be inhibited by Del-1 depletion, which restores TAM sensitivity. Thus, therapeutic strategies that target Del-1 may be effective for the treatment of hormone-resistant breast cancer.