Explore the vast range of titles available.

Tumor-associated myeloid-derived cells (MDCs) significantly impact cancer prognosis and treatment responses due to their remarkable plasticity and tumorigenic behaviors. Here, we integrate single-cell RNA-sequencing data from different cancer types, identifying 29 MDC subpopulations within the tumor microenvironment. Our analysis reveals abnormally expanded MDC subpopulations across various tumors and distinguishes cell states that have often been grouped together, such as TREM2+ and FOLR2+ subpopulations. Using deconvolution approaches, we identify five subpopulations as independent prognostic markers, including states co-expressing TREM2 and PD-1, and FOLR2 and PDL-2. Additionally, TREM2 alone does not reliably predict cancer prognosis, as other TREM2+ macrophages show varied associations with prognosis depending on local cues. Validation in independent cohorts confirms that FOLR2-expressing macrophages correlate with poor clinical outcomes in ovarian and triple-negative breast cancers. This comprehensive MDC atlas offers valuable insights and a foundation for futher analyses, advancing strategies for treating solid cancers. Tumour-associated myeloid cells have been linked to patient outcome and treatment response in multiple cancer types. Here, the authors use deconvolution of single cell RNA-sequencing data to identify myeloid populations which are prognostic across cancer types.

Uterine Carcinosarcomas (UCS) are a rare type of cancer composed of an admixture of high-grade carcinomatous and sarcomatous elements. Clinicopathological prognostic factors in UCS are well established, but studies that approach the impact of biomarkers in this unusual disease are scarce. The study objective was to evaluate the prevalence and prognostic impact of a panel of prominent biomarkers in uterine carcinosarcoma (UCS) using an immunohistochemical characterization with four biomarkers. The internal database of a single Brazilian institution was carefully explored to select women diagnosed with UCS who were submitted to surgery and postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing UCS samples were evaluated by immunohistochemistry for L1CAM, CDX2, p53 and microsatellite instability markers. A total of 57 cases were included. The mean age was 65.3 years (standard deviation, SD 7.0). L1CAM was negative (score 0, no staining) in 27 (47.4%) patients. Of L1CAM-positive, 10 (17.5%) showed weak (score 1, <10%), 6 (10.5%) showed moderate (score 2, between 10-50%), and 14 (24.6%) showed strong L1CAM staining (score 3, ≧50%). dMMR occurred in 3 (5.3%) cases. The p53 was aberrantly expressed in 15 (26.3%) tumors. CDX2 was positive in 3 (5.3%) patients. The three-year progression-free survival (PFS) rate in the general population of the study was 21.2% (95% CI: 11.7-38.1) and the three-year overall survival (OS) rate was 29.4% (95% CI: 18.1-47.6). By multivariate analysis, the presence of metastases and CDX2-positive were significantly associated with poorer PFS (p < 0.001 and p = 0.002, respectively) and OS (p < 0.001 and p = 0.009, respectively). The strong influence of CDX2 on prognosis requires further investigation. Biological or molecular variability may have impaired the assessment of the impact of the other markers on survival.

Breast cancer (BC) is a prevalent form of cancer affecting women worldwide. However, the effectiveness of current BC drugs is limited by issues such as systemic toxicity, drug resistance, and severe side effects. Consequently, there is an urgent need for new therapeutic targets and improved tumor tracking methods. This study aims to address these challenges by proposing a strategy for identifying membrane proteins in tumors that can be targeted for specific BC therapy and diagnosis. The strategy involves the analyses of gene expressions in breast tumor and non-tumor tissues and other healthy tissues by using comprehensive bioinformatics analysis from The Cancer Genome Atlas (TCGA), UALCAN, TNM Plot, and LinkedOmics. By employing this strategy, we identified four transcripts (LRRC15, EFNA3, TSPAN13, and CA12) that encoded membrane proteins with an increased expression in BC tissue compared to healthy tissue. These four transcripts also demonstrated high accuracy, specificity, and accuracy in identifying tumor samples, as confirmed by the ROC curve. Additionally, tissue microarray (TMA) analysis revealed increased expressions of the four proteins in tumor tissues across all molecular subtypes compared to the adjacent breast tissue. Moreover, the analysis of human interactome data demonstrated the important roles of these proteins in various cancer-related pathways. Taken together, these findings suggest that LRRC15, EFNA3, TSPAN13, and CA12 can serve as potential biomarkers for improving cancer diagnosis screening and as suitable targets for therapy with reduced side effects and enhanced efficacy.

Objective To examine the prevalence and prognostic role of tumor microenvironment (TME) markers in uterine carcinosarcoma (UCS) through immunohistochemical characterization. Methods The internal database of our institution was queried out for women with UCS who underwent surgery and thereafter postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing surgical samples of UCS from 57 women were assessed by immunohistochemistry for CD3, CD4, CD8, FOXP3, PD-1, PD-L1, and PD-L2. Results The mean age was 65.3 years (range, 49 to 79 years). For the epithelial component (E), CD3_E and CD4_E were highly expressed in 38 (66.7%) and in 40 (70.1%) patients, respectively, and were significantly associated with more advanced stages ( p  = 0.038 and p  = 0.025, respectively). CD8_E was highly expressed in 42 (73.7%) patients, FOXP3_E 16 (28.1%), PD-1_E 35 (61.4%), PD-L1_E 27 (47.4%) and PD-L2_E 39 (68.4%). For the sarcomatous component (S), the prevalence of high expression was: CD3_S 6 (10.5%), CD4_S 20 (35.1%), CD8_S 44 (77.2%), FOXP3_S 8 (14%), PD-1_S 14 (24.6%), PD-L1_S 14 (24.6%) and PD-L2_S 8 (14%). By multivariate analysis, the CD8/FOXP3_S ratio ( p  = 0.026), CD4_E ( p  = 0.010), PD-L1_E ( p  = 0.013) and PD-L1_S ( p  = 0.008) markers significantly influenced progression-free survival. CD4/FOXP3_S ratio ( p  = 0.043), PD-1_E ( p  = 0.011), PD-L1_E ( p  = 0.036) and PD-L1_S ( p  = 0.028) had a significant association with overall survival. Conclusion Some differences in UCS clinical outcomes may be due to the subtype of TILs and PD-1/PD-L1 axis immune checkpoint signaling.

Background NKX2.5 is a transcription factor transiently expressed during thyroid organogenesis. Recently, several works have pointed out the oncogenic role of NKX2.5 in a variety of tumors. We therefore hypothesized that NKX2.5 could also play a role in thyroid cancer. Methods The validation of NKX2.5 expression was assessed by immunohistochemistry analysis in a Brazilian case series of 10 papillary thyroid carcinoma (PTC) patients. Then, the long-term prognostic value of NKX2.5 and its correlation with clinicopathologic features of 51 PTC patients was evaluated in a cohort with 10-years follow-up (1990–1999). Besides, the effect of NKX2.5 overexpression on thyroid differentiation markers and function was also investigated in a non-tumor thyroid cell line (PCCL3). Results NKX2.5 was shown to be expressed in most PTC samples (8/10, case series; 27/51, cohort). Patients who had tumors expressing NKX2.5 showed lower rates of persistence/recurrence ( p  = 0.013). Overexpression of NKX2.5 in PCCL3 cells led to: 1) downregulation of thyroid differentiation markers (thyrotropin receptor, thyroperoxidase and sodium-iodide symporter); 2) reduced iodide uptake; 3) increased extracellular H 2 O 2 generation, dual oxidase 1 mRNA levels and activity of DuOx1 promoter. Conclusions In summary, NKX2.5 is expressed in most PTC samples analyzed and its presence correlates to better prognosis of PTC. In vitro, NKX2.5 overexpression reduces the expression of thyroid differentiation markers and increases ROS production. Thus, our data suggests that NKX2.5 could play a role in thyroid carcinogenesis.

This study aimed to investigate the influence of immunohistochemical (IHC) biomarkers in the response to neoadjuvant chemotherapy (NACT) and survival outcomes in the subset of locally advanced triple-negative breast cancer (TNBC). The epidermal growth factor receptor (EGFR), androgen receptor (AR), cytokeratins (CK5/6, CK14 and CK17), Ki67 and p53 immunohistochemistry were evaluated on 171 cases of TNBC submitted to NACT and subsequently to surgery. Intensity and percentage of the expression of these biomarkers were combined to formulate a specific score, that was correlated with prognostic features and assessed for survival outcomes. Most patients had advanced clinical-stage tumors (stage III: 83.6%; cT3/T4: 85.9%; cN1-3: 71.3%). The predominant histological subtype was high-grade (67.3%) and invasive ductal carcinoma (93.6%). The residual cancer burden (RCB) 0-1 corresponded to 28.7% of cases and low-risk lymph node ratio (LNR) represented 77.2%. High Ki67 expression only showed a significant correlation with grade 3 tumors (p = 0.0157). CK5/6 was observed in 16% (27/169), CK14 was positive in 10.1% (17/169), CK17 in 91.1% (153/168), p53 in 52.6% (70/133), EGFR in 92.9% (157/169 cases), AR in 13% (22/169) and Ki67 index was scored ≥40% in 57.9% (95/165). No IHC biomarker significantly impacted response or survival. Regarding the analysis of the outcomes of event-free survival (EFS) and overall survival (OS), clinical stage (p = 0.014 and p = 0.042, respectively), RCB (p < 0.0001 and p <0.0001, respectively) and LNR (p <0.0001 and p <0.0001, respectively) showed significant association. No IHC biomarker evaluated showed a significant association with a response or survival outcomes in TNBC patients. Clinical stage, LNR and RCB stood out for strongly influencing survival.

We report two rare cases of breast cancer in men treated with modified radical mastectomy. The patients were aged 67 and 45 years at the time of diagnosis. Tumor sizes were 2 cm and 8 cm in the older and younger patient, respectively. The histopathologic diagnosis was infiltrating ductal carcinoma in the first patient and infiltrating papillary carcinoma in the second patient. Immunohistochemical tests demonstrated estrogen and progesterone receptor positivity and HER2/c-erbB-2 negativity in both cases. The rarity of these cases is noted, in view of their uncommon occurrence at an early age in men and their immunophenotypic positivity, similar to breast cancer in women.

Background Uterine carcinosarcomas (UCS) are rare and aggressive gynecological tumors and the description of biomarkers that can help guide targeted treatments in this disease is a critical gap in current medical research. This study aims to measure the prevalence of trophoblast cell-surface antigen 2 (Trop-2) and folate receptor alpha (FRα) in UCS and evaluate their prognostic significance. Methods This retrospective analysis examined data from female patients diagnosed with UCS who underwent surgery followed by carboplatin and paclitaxel chemotherapy between January 2012 and December 2020. Tissue microarrays from 89 samples were assessed for Trop-2 and FRα expression by IHC. High positivity was defined as a score of ≥ 50% of tumor cells with strong staining intensity for Trop-2 and ≥ 75% with medium or strong staining intensity for FRα. Sociodemographic and clinical features were analyzed alongside progression-free survival (PFS) and overall survival (OS) outcomes. Results The mean age at diagnosis was 66.2 years (Standard Deviation, SD: 7) and the mean body mass index was 28.7 kg/m² (SD: 6.2). Non-white women accounted for 71.6% of cases. Heterologous subtype corresponded to 63.0% of cases, and lymphovascular invasion was observed in 59.2%. Complete resection (R0) was achieved in 66.3% of cases. High expression of Trop-2 and FRα was found in 49.4% and 17.4% of epithelial components, respectively, with no high positivity in sarcomatous components. Negative margins were more common in stage I/II disease ( p  = 0.001), and FRα overexpression correlated with Trop-2 overexpression ( p  = 0.007). On multivariate analysis, advanced stage ( p  = 0.015) and incomplete resection ( p  < 0.001) predicted shorter PFS, while both factors also independently worsened OS ( p  = 0.013 and p  = 0.001, respectively). Lymphadenectomy was associated with improved OS ( p  = 0.025). Conclusion Complete resection and advanced stage were suggested as prognostic factors in UCS. FRα and Trop-2 are increasingly recognized as therapeutic targets and their elevated expression levels in the epithelial component of UCS are promising, although not associated with prognosis in this cohort.

This study aimed to compare the clinical behavior, clinicopathological and sociodemographic characteristics of patients with early-stage triple-negative breast cancer (TNBC) who belong to the HER2-low and HER2-zero subgroups. This study involved a thorough search in the internal database of a single Brazilian institution to identify women with TNBC who underwent neoadjuvant chemotherapy (NACT) followed by curative surgery within the period from January 2010 to December 2014. HER2 analysis through immunohistochemistry (IHC) and, if required, amplification by in situ hybridization, was conducted using core biopsy samples. The study assesses outcomes of residual cancer burden (RCB), event-free survival (EFS), and overall survival (OS). A total of 170 cases were analyzed, with a mean age of 51.4 years (standard deviation, SD 11.2). The HER2 status was categorized as IHC 0, 1+, or 2+ in 80 (47.1%), 73 (42.9%), and 17 (10%) patients, respectively. No significant differences were observed in the prevalence of clinical pathological characteristics among the subgroups. The absence of significant results for clinicopathological and demographic features hindered the multivariate analysis of HER2 subgroups. Similarly, no significant differences were found in the RCB, EFS, and OS outcomes between HER2 subgroups. The findings of this study suggest that, in early-stage TNBC, the clinical behavior and survival outcomes of the HER2-low subgroup may not differ significantly from those of the HER2-zero subgroup.

This study aimed to assess the frequency and prognostic significance of programmed cell death ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) subtypes in advanced triple-negative breast cancer (TNBC). A database search was conducted to identify women with previously untreated locally recurrent inoperable or metastatic TNBC treated between January 2018 and December 2022. The inclusion criteria required formalin-fixed paraffin-embedded samples aged less than four years. PD-L1 expression was evaluated using the PD-L1 IHC 22C3 pharmDx assay, and the combined positive score (CPS) was calculated. TIL subtypes were assessed using immunohistochemical staining. The study included 150 patients, with a median age of 51.5 years. The majority of patients were younger than 65 years, postmenopausal, non-white, and had metastatic TNBC. CPS≥10 was observed in 20.9% of cases, mainly in postmenopausal women. No significant differences were found in demographic characteristics and clinicopathological variables across PD-L1 subgroups. Tumors with PD-L1 CPS≥10 had higher expression of CD3+, CD4+, and CD8+ TIL subtypes. Most patients received first-line chemotherapy, with smaller proportions undergoing second, third, and fourth-line treatments. No statistically significant differences were observed in median progression-free survival (PFS) or overall survival (OS) across PD-L1 subgroups in this cohort of chemotherapy-treated patients. This study provides insights into the expression profiles of PD-L1 and TIL subtypes in advanced TNBC. The PD-L1 CPS status did not significantly affect survival outcomes, but variations in TIL subtype composition were observed based on PD-L1 CPS status.