Novel lncRNAs Co-Expression Networks Identifies LINC00504 with Oncogenic Role in Luminal A Breast Cancer Cells.

Long non-coding RNAs (lncRNAs) are functional transcripts with more than 200 nucleotides. These molecules exhibit great regulatory capacity and may act at different levels of gene expression regulation. Despite this regulatory versatility, the biology of these molecules is still poorly understood. Computational approaches are being increasingly used to elucidate biological mechanisms in which these lncRNAs may be involved. Co-expression networks can serve as great allies in elucidating the possible regulatory contexts in which these molecules are involved. Herein, we propose the use of the pipeline deposited in the RTN package to build lncRNAs co-expression networks using TCGA breast cancer (BC) cohort data. Worldwide, BC is the most common cancer in women and has great molecular heterogeneity. We identified an enriched co-expression network for the validation of relevant cell processes in the context of BC, including LINC00504. This lncRNA has increased expression in luminal subtype A samples, and is associated with prognosis in basal-like subtype. Silencing this lncRNA in luminal A cell lines resulted in decreased cell viability and colony formation. These results highlight the relevance of the proposed method for the identification of lncRNAs in specific biological contexts.

Association between SNP rs527616 in lncRNA AQP4-AS1 and susceptibility to breast cancer in a southern Brazilian population.

Breast cancer (BC) is the leading cause of death by this disease in women worldwide. Among the factors involved in tumorigenesis, long non-coding RNAs (lncRNAs) and their differential expression have been associated. Differences in gene expression may be triggered by variations in DNA sequence, including single nucleotide polymorphisms (SNPs). In the present study, we analyzed the rs527616 (C>G), located in the lncRNA AQP4-AS1, using PCR-SSP in 306 BC patients and 312 controls, from a Brazilian population. In the BC group, the frequency found for CG heterozygotes was above the expected and the overdominant model is the best one to explain our results (OR: 1.70, IC 95%: 1.23-2.34, P<0.001). Furthermore, the SNP were associated with age at BC diagnosis and the risk genotype more frequent in the older age group. According to TCGA data, AQP4-AS1 is down-regulated in BC tissue, and the overexpression is associated with better prognoses, including Luminal A, HER2-, stage 1 of disease and smaller tumor. In conclusion, the CG genotype is associated with increased susceptibility in the southern Brazilian population. This SNP is mapped in the lncRNA AQP4-AS1, showing differential expression in BC samples. Based on these results, we emphasize the potential of the role of AQP4-AS1 in cancer.

Integrated analysis of label-free quantitative proteomics and bioinformatics reveal insights into signaling pathways in male breast cancer.

Male breast cancer (MBC) is a rare malignancy that accounts for about 1.8% of all breast cancer cases. In contrast to the high number of the "omics" studies in breast cancer in women, only recently molecular approaches have been performed in MBC research. High-throughput proteomics based methodologies are promisor strategies to characterize the MBC proteomic signatures and their association with clinico-pathological parameters. In this study, the label-free quantification-mass spectrometry and bioinformatics approaches were applied to analyze the proteomic profiling of a MBC case using the primary breast tumor and the corresponding axillary metastatic lymph nodes and adjacent non-tumor breast tissues. The differentially expressed proteins were identified in the signaling pathways of granzyme B, sirtuins, eIF2, actin cytoskeleton, eNOS, acute phase response and calcium and were connected to the upstream regulators MYC, PI3K SMARCA4 and cancer-related chemical drugs. An additional proteomic comparative analysis was performed with a primary breast tumor of a female patient and revealed an interesting set of proteins, which were mainly involved in cancer biology. Together, our data provide a relevant data source for the MBC research that can help the therapeutic strategies for its management.

Marking axillary nodes with 4% carbon microparticle suspension before neoadjuvant chemotherapy improves sentinel node identification rate and axillary staging.

BACKGROUND AND OBJECTIVES: Marking positive lymph nodes (LNs) before neoadjuvant chemotherapy (NAC) may improve the accuracy of sentinel lymph node biopsy (SLNB). The aim of this study was to determine the feasibility of marking LNs with 4% carbon microparticle suspension (CMS) before NAC and to evaluate if this technique would improve the SLNB identification rate. METHODS: A prospective study of patients with cT1-T4, cN1-N2 breast cancer who underwent US-guided fine-needle aspiration biopsy (FNAB) of suspected LNs and concomitant marking with 4% CMS was performed. After NAC, LNs marked with 4% CMS and those marked with Patent Blue V dye (PBV) were identified and resected. RESULTS: Of the 123 patients included, 74 (60.1%) had positive LNs at FNAB. During axillary surgery, 4% CMS was identified in 121 of 123 patients (98.3%) and blue sentinel LNs in 91% (112 of 123 patients) (P = .0103). Comparing isolated results of PBV and 4%CMS + PBV, the association was better in identifying positive LNs (72.2% vs 97.7%) (P = .02). CONCLUSION: The association of 4% CMS and PBV is feasible and significantly increased the identification rate of positive LNs. 4% CMS may play an important role as a complementary technique in patients submitted to NAC.

A genetic variant in microRNA-146a is associated with sporadic breast cancer in a Southern Brazilian Population.

MicroRNAs (miRNAs) play an essential role in gene expression and affect the development of tumours, including breast cancer (BC). Polymorphisms in miRNA genes can affect the interaction of miRNAs with their target messenger RNA by interfering, creating or disrupting target sites. The single nucleotide polymorphism (SNP) rs2910164, located in the seed region of miR146a, was shown to be associated with BC among different populations. In the present study, we investigated whether rs2910164 is associated with BC in 326 patients and 411 controls from a Brazilian population of predominantly European ancestry. The presence of the allele rs2910164*C was associated with an increased risk of BC (OR=1.4, 95% CI=1.03-1.85, p = 0.03). We also analysed publicly available RNA-seq data to evaluate if miR146a is differentially expressed in different subtypes of BC. Genotyping was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP). By leveraging public data from TCGA database, we analysed 461 patients and found that miR146a is significantly more expressed in BC than in non-tumor tissue (1.47 fold, p = 0.02) and is expressed to a greater degree in aggressive BC subtypes.

Association of FOSL1 copy number alteration and triple negative breast tumors.

Copy number alterations (CNAs) are a frequent feature in human breast cancer, and one of the hallmarks of genomic instability. The FOSL1, GSTP1 and CCND1 genes are located at 11q13, a cytoband commonly affected by CNA in breast cancer, with relevant function in progression and invasion. Our main goal was to analyze CNAs of these genes and determine their association with breast cancer subtypes. Seventy-three cases of invasive breast tumors [52 Luminal, 7 HER2+ and 14 triple negative (TNBC) subtypes] were analyzed by TaqMan assays. CNAs were observed for all genes, with gains more frequently observed. Gains of the FOSL1 gene were observed in 71% of the cases. This gene was the only one with a statistically significant difference (p<0.001) among tumor subtypes, with increased copy number in TNBC compared to luminal and HER2+. No significant association of CNA and clinical and histopathological parameters from the patients was observed. Additional studies in larger breast cancer patient cohorts based on more refined molecular subtypes are necessary to confirm the observed association of FOSL1 gain with aggressive breast tumors phenotypes.

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

PURPOSE: Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. METHODS: The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. RESULTS: Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. CONCLUSIONS: In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.

Trends in breast cancer surgery at Brazil's public health system.

BACKGROUND AND OBJECTIVES: To analyze time trend patterns in Breast Cancer (BC) surgeries performed at Brazil's Public Health System, known as SUS from 2008 to 2014. METHODS: Ecological study of time series, based on the database system from SUS. Information on surgical procedures performed for BC treatment was collected. Analysis of the absolute number of surgeries was performed using Poisson Regression through Jointpoint Regression, and the trends were calculated through the annual percentage change (APC), with a confidence interval (CI) of 95%, and statistical significance when P < 0.05. RESULTS: Data analysis from 193.596 breast surgeries revealed a reduced number of simple mastectomies (APC -4.4%; CI -7.4 to -1.4; P < 0.05); stable trends in radical mastectomy with lymphadenectomy (APC -1.0%; CI -2.4 to 0.5; P = 0.1) and breast conserving surgery (APC 0.4%; CI -1.6 to 2.4; P = 0.6). Also, we observed a reduced number of axillary lymphadenectomy dissection (APC -16.8%; CI -26.8 to -5.4; P < 0.05); increased trends in breast reconstruction with implants after 2011 (APC 9.1%; CI 0.1-18.8; P < 0.05) and with flaps after 2012 (APC 61.3%; CI 41.3-84.0; P < 0.05). The overall rate of patients with breast reconstruction increased from 15% in 2008 to 29.2% in 2014. CONCLUSIONS: We found a significant increase in breast reconstruction in public health system in Brazil, and also a reduction in simple mastectomy and axillary lymphadenectomy.

Long-Term Comparison of Aesthetical Outcomes After Oncoplastic Surgery and Lumpectomy in Breast Cancer Patients.

BACKGROUND: Lumpectomy may result in major deformities and asymmetries in approximately one-third of patients. Although oncoplastic surgery (OP) could be a useful alternative to avoid them, lack of strong data is causing some debate. The purpose of this study was to compare aesthetic outcomes in patients undergoing OP versus lumpectomy using three different assessment methods. METHODS: A total of 122 patients were included in this cross-sectional multicentric study; 57 underwent OP (46.7 %), and 65 underwent lumpectomy (53.3 %). Two breast surgeons and two plastic surgeons from different institutions using the Garbay scale independently evaluated aesthetic outcomes. BCCT.core software was applied in both groups, and the patients evaluated their aesthetic outcomes answering a questionnaire about their satisfaction rate. RESULTS: OP group had a higher proportion of excellent aesthetic results according to the BCCT.core software analysis (p = 0.028) and the specialists (p = 0.002). Multifactorial analyses showed that age ≥70 years (RP = 6.02; 95 % confidence interval [CI] 1.73-21.0; p = 0.005), tumors in the medial, inferior, and central quadrants (RP = 4.21; 95 % CI 1.88-9.44; p < 0.001), and large breasts (RP = 7.55; 95 % CI 2.48-23.0; p < 0.001) were significant risk factors for poor aesthetic outcomes after lumpectomy. The patients classified their results as better than those by the specialists and by the software, with no statistical difference between the groups. CONCLUSIONS: Excellent aesthetic results were more frequent in the OP group according to BCCT.core software analysis and specialists. In addition, some clinical conditions and tumor locations in the breast can be considered risky factors for poor aesthetic outcomes in lumpectomy.

Nonprocessed adipose tissue graft in the treatment of peri-implant osseous defects in the rabbit's tibiae: a pilot study.

We hypothesized that a new technique using nonprocessed adipose tissue could regenerate bone around dental implants. Eighteen rabbits received 1 implant per tibia surrounded by a surgically created osseous defect. The defects were assigned for treatment into 3 groups: C, AT, and AB. The percentages of bone-to-implant contact were 17.64% ± 16.22% (AB), 3.54% ± 7.08% (AT), and 12.71% ± 10.11% (C) (ρ = 0.25). The use of adipose tissue around surgically created peri-implant osseous defects interferes with bone formation.

Training in oncoplastic surgery for mastologists.

OBJECTIVE: The radical change in the treatment of breast cancer has promoted the necessity for more comprehensive training of the professionals involved, ensuring the preservation of oncological safety while also allowing for cosmetic interventions to benefit breast cancer survivors. The aim of this study was to present the methods employed in the training of breast surgeons, highlighting the importance of oncoplasty and breast reconstruction. METHODS: A literature review was conducted in two databases, identifying articles related to medical education in the context of oncoplastic surgery and breast reconstruction. We also assessed the Brazilian experience in oncoplastic centers. RESULTS: The basis for educational discussions was derived from 16 articles. We observed approaches that included hands-on courses utilizing simulator models, porcine models, cadaver labs, and fellowship programs. Positive outcomes were observed in Brazil, a fact based on seven oncoplasty training centers for senior mastologists and five training centers for junior mastologists. From 2009 to 2023, an estimated 452 seniors and 42 juniors received training, representing approximately 30% of mastologists in Brazil who have acquired training and experience in oncoplasty. CONCLUSION: Despite the limited number of publications on training methods, oncoplastic centers have made significant progress in Brazil, establishing a successful model that can be replicated in other countries.

Three-dimensional Simulation on Patient-reported Outcomes Following Oncoplastic and Reconstructive Surgery of the Breast: A Randomized Trial.

Background: Three-dimensional (3D) imaging using computer simulations is an evolving technology. There is a lack of strong data on the use of this technology for oncoplastic (OP) and reconstructive surgery. Methods: A prospective, randomized, single-center trial including breast cancer patients undergoing OP or mastectomy with immediate breast reconstruction with implant (IBR) enrolled from November 2019 to October 2021 at the Hospital Nossa Senhora das Graças, Breast Unit in Curitiba, Brazil. Both patients undergoing OP and those in the IBR group were randomized to undergo 3D imaging and simulation of postoperative results (intervention group) or 3D imaging without simulation (control group). All patients were invited to complete a patient-reported outcome (BREAST-Q) expectations module and breast reconstruction or reduction/mastopexy module before and 6 months after surgery. Results: A total of 96 patients were enrolled. Sixty-nine patients (45 OP and 24 IBR) completed the pre- and postoperative questionnaires and were randomized for the simulation. Women in the OP group had higher expectations for breast appearance when clothed than those in the IBR implant group (93.4 ± 16.3 versus 82.9 ± 26.5; P = 0.03). The intervention group was more satisfied with information than the control group (P = 0.021). Both patients who underwent OP and IBR believed that the 3D simulation helped them understand the surgical process (86.6% and 75%, respectively). Conclusions: Preoperative 3D simulation significantly improved patient's satisfaction with information and did not decrease postoperative satisfaction with the outcomes. The incorporation of preoperative 3D simulation may be a valuable tool in breast reconstruction.

Amplification and deletion of the RAPH1 gene in breast cancer patients.

Lamellipodin protein (Lpd), encoded by the RAPH1 gene, modulates the assembly of actin cytoskeleton through its binding to the Ena/VASPs proteins, and acts in cellular motility and lamelipodial protrusion. The region where RAPH1 gene is located (2q33) is deleted in various types of cancer and the gene expression changes in tumors when compared to normal tissues. Amplifications and deletions of the RAPH1 gene were investigated in breast carcinoma samples, in order to determine the possible relationship of the gene with breast cancer tumorigenesis and lymph node metastasis. RAPH1 gene alterations were determined by relative quantification, standard curve method using Real-time PCR technique in samples of tumor and peripheral blood from 52 patients. Regression and correlation analyses were conducted using gene alterations and clinicopathological data. All samples analyzed were altered, with 63.5 % deletion cases and 36.5 % amplification cases. The logistic regression and correlation analysis with clinicopathological data did not show significant results. The results suggest that although the RAPH1 gene was deleted or amplified in all samples, the Lpd does not seem to play a major role in tumorigenesis of mammary carcinomas and probably other proteins, also involved in the process of cellular motility and metastasis, are acting more effectively for or against the migration of breast tumor cells.

Fragmented adipose tissue transplanted to craniofacial deformities induces bone repair associated with immunoexpression of adiponectin and parathyroid hormone 1-receptor.

Objective : This study analyzed the influence of autogenous white adipose tissue on bone matrix development in critical-size defects created in rabbit calvaria. Materials and methods : A 15-mm-diameter defect was created in the calvaria of 42 rabbits. Twenty-one rabbits were treated with 86 mm(3) of immediate transplant of fragmented white subcutaneous adipose tissue (WSAT); the others constituted the control group (sham). The animals were euthanized at 7, 15, and 40 days postsurgery (n = 7), and the histological data were analyzed by histomorphometry and immunohistochemistry using the anti-adiponectin and parathyroid hormone 1-receptor (PTH1R) antibodies. Results : The calvariae treated with fragmented WSAT demonstrated significant bone formation. These results coincided with the significant presence of immunopositivity to adiponectin and PTH1R in loci, which in turn coincided with the increase in bonelike matrix deposited both in fat tissue stroma and adipocytes' cytoplasm. In contrast, the control group revealed a small amount of bone-matrix deposition and presented scarce PTH1R expression and a lack of immunostain for adiponectin. Conclusion : These results indicate that transplant of fragmented white subcutaneous adipose tissue may be an alternative to treatment of craniofacial bone deformities because adipose tissue suffers from osseous metaplasia and exhibits immunoexpression of the adiponectin and PTH1R, which are proteins associated with bone metabolism.

Fragmented adipose tissue graft for bone healing: histological and histometric study in rabbits' calvaria.

OBJECTIVE: The adipose tissue represents an important reservoir of stem cells. There are few studies in the literature with which to histologically evaluate whether or not the adipose tissue graft is really a safe option to achieve bone repair. This study histologically analyzed the effect of fragmented autogenous adipose tissue grafts on bone healing in surgically created, critical-size defects (CSD) in a rabbit's calvaria. STUDY DESIGN: Forty-two New Zealand rabbits were used in this study. CSD that were 15 mm in diameter were created in the calvarium of each animal. The defects were randomly divided into two groups: in Group C (control), the defect was filled only by a blood clot and, in Group FAT (i.e., fragmented adipose tissue), the defect was filled with fragmented autogenous adipose tissue grafts. The groups were divided into subgroups (n = 7) for euthanasia at 7, 15, and 40 days after the procedure had been conducted. Histologic and histometric analyses were performed. Data were statistically analysed with ANOVA and Tukey's tests (p < 0.05). RESULTS: The amount of bone formation did not show statistically significant differences seven days after the operation, which indicates that the groups had similar amounts of mineral deposition in the earlier period of the repair. Conversely, a significant of amount of bone matrix deposition was identified in the FAT group at 15 and 40 days following the operation, both on the border and in the body of the defect. Such an outcome was not found in the control group. CONCLUSION: In this study, an autologous adipose tissue graft may be considered as likely biomaterial for bone regeneration, since it positively affected the amount of bone formation in surgically created CSD in the rabbits' calvaria 40 days after the procedure had been performed. Further investigations with a longer time evaluation are warranted to determine the effectiveness of autologous adipose tissue graft in the bone healing.

Oncological safety of nipple-sparing mastectomy after neoadjuvant chemotherapy: a systematic review.

BACKGROUND: the use of nipple-sparing mastectomy (NSM) in local advanced breast cancer after neoadjuvant chemotherapy (NQT) is increasing, despite few studies on the subject. The aim of this systematic review was to determine the safety of NSM after neoadjuvant chemotherapy. METHODS: for this systematic review we searched MEDLINE; Cochrane; Scientific Electronic Library Online (SciELO); Embase and Scopus. A literature search of all original studies including randomized controlled trials, cohort studies and case-control studies comparing women undergoing NSM after neoadjuvant chemotherapy for breast cancer was undertaken. Outcomes were locoregional recurrence (LRR), nipple recurrence and distant recurrence (DR). Data analysis was undertaken to explore the safety of NSM after NQT. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on PROSPERO, number CRD42021276778. FINDINGS: a total of 437 articles were identified. Four articles were included with 1466 patients all of which had a high to serious risk of overall bias. Local recurrence in the NSM after the NQT group ranged from zero to 9.8%. Nippleareolar complex (NAC) recurrence ranged from zero to 2.1%. The distant recurrence rate ranged from 6.5% to 16%. Due to the lack of pattern among the control groups, it was not possible to perform a meta-analysis. INTERPRETATION: this review provides information for decision making in performing NSM after NQT. Despite the low rates of local recurrence and patients should be counseled about limited oncological information.

Prospective study: Impact of breast magnetic resonance imaging on oncoplastic surgery and on indications of mastectomy in patients who were previously candidates to breast conserving surgery.

Background: Routine use of magnetic resonance imaging (MRI) in the staging of patients with early breast cancer is still controversial. Oncoplastic surgery (OP) allows for wider resections without compromising the aesthetic results. This study aimed to assess the impact of preoperative MRI on surgical planning and on indications of mastectomy. Methods: Prospective study including T1-T2 breast cancer patients treated between January 2019 and December 2020 in the Breast Unit of the Hospital Nossa Senhora das Graças in Curitiba, Brazil. All patients had indication for breast conserving surgery (BCS) with OP and did a breast MRI after conventional imaging. Results: 131 patients were selected. Indication for BCS was based on clinical examination and conventional imaging (mammography and ultrasound) findings. After undergoing breast MRI, 110 patients (84.0%) underwent BCS with OP and 21 (16.0%) had their surgical procedure changed to mastectomy. Breast MRI revealed additional findings in 52 of 131 patients (38%). Of these additional findings, 47 (90.4%) were confirmed as invasive carcinoma. Of the 21 patients who underwent mastectomies, the mean tumor size was 2.9 cm (± 1,7cm), with all having additional findings on breast MRI (100% of the mastectomies group vs 28.2% of the OP, p<0.01). Of the 110 patients submitted to OP, the mean tumor size was 1,6cm (± 0,8cm), with only 6 (5.4%) presenting positive margins at the final pathology assessment. Conclusion: Preoperative breast MRI has an impact on the OP scenario, bringing additional information that may help surgical planning. It allowed selecting the group with additional tumor foci or greater extension to convert to mastectomy, with a consequent low reoperation rate of 5.4% in the BCS group. This is the first study to assess the impact of breast MRI in the preoperative planning of patients undergoing OP for the treatment of breast cancer.

Uncertainties and controversies in axillary management of patients with breast cancer.

The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register.

Bone healing in critical-size defects treated with immediate transplant of fragmented autogenous white adipose tissue.

This study analyzed the influence of fragmented autogenous white subcutaneous adipose tissue (WSAT) on bone healing in critical-size defects created in rabbit calvaria. A 15-mm diameter defect was created in the calvaria of 42 rabbits, which were treated with 86 mm3 WSAT grafts or filled only with blood clots (control). Animals were euthanized at 7, 15, and 40 days postsurgery (n = 7), and the data were analyzed using histomorphometry and immunohistochemistry using the anti-CD34 and bone morphogenetic protein-2 (BMP2) antibodies. The calvaria treated with only blood clots demonstrated positivity to CD34 concentrated in endothelial cells, whereas the BMP2 were restricted to the borders of the defects. In contrast, the group treated with WSAT revealed fatty cells exhibiting positivity to BMP2 both in membrane and cytoplasm and intense quantities of stromal spindle cells that exhibited positivity to CD34 simultaneously to BMP2; these results together coincided with a larger bone matrix deposited in all postsurgery periods analyzed. These results revealed that the WSAT may be an alternative to craniofacial bone reconstruction because the adipose tissue exhibited prominent immunoexpression of BMP2, which was coexpressed with stromal CD34+ cells, indicating the plasticity of CD34+ stem cells into osteoblasts, and in the adipocytes, facts that suggest bone tissue development through cellular transdifferentiation from adipocytes.