CD47 functions as a dominant anti-engulfment signal on tumour cells and is overexpressed in various malignant tumours. However, the expression and functional significance of CD47 in triple-negative breast cancer (TNBC) is not completely understood. In the present study, CD47 was demonstrated to be overexpressed in TNBC solid tumours. Moreover, increased CD47 expression was significantly associated with an advanced tumour-node-metastasis stage, lymph node involvement and recurrence. Moreover, CD47 was an unfavourable and independent prognostic factor for 5-year disease-free survival in patients with TNBC. In addition, the expression of CD47 was associated with several markers of epithelial-mesenchymal transition (EMT). The present study was the first to demonstrate an association between increased expression of CD47 with EMT and poor prognosis of TNBC. Thus, CD47 may be a potential prognostic biomarker and therapeutic target for TNBC.

Background Avoiding the phagocytosis by tumor-associated macrophages (TAMs) is necessary for the growth and metastasis of solid tumors. CD47 binds to the receptor signal-regulatory protein-α (SIRP-α) on the macrophages to avoid normal phagocytosis. In this study, we evaluated the expression and prognostic significance of CD47 and CD68-labeled TAMs in breast cancer solid tumors. Methods Two hundred seventeen cases of breast cancer tissues and 40 cases of benign breast lesions were collected for immunohistochemical staining of CD47 and CD68. Results Both of the CD47 and CD68 expression were significantly higher in breast cancer tissues (P < 0.001), and associated with multiple clinicopathological parameters in breast cancer (P < 0.05). However, CD47 or CD68 expression alone was not an independent predictor of poor DFS in multivariate survival analysis (P > 0.05). Interestingly, combined high expression of CD47 and CD68 (CD47highCD68high) not only had a significant association with advanced TNM stage, histological grade, LNM, ER status, PR status and recurrence (P < 0.05), but also displayed a poorer 5-DFS (P = 0.011). Strikingly, CD47highCD68high served as a novel independent prognostic factor for poor DFS compared to the expression of CD47 or CD68 alone (P = 0.045). Furthermore, our study also showed for the first time that the prognostic significance of CD47highCD68high not only in breast cancer in general, but also in hormone receptor-negative breast cancer in particular. Conclusions Combined detection of CD47 and CD68 may provide guidance for the prognosis of breast cancer, especially hormone receptor-negative breast cancer.

Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma presenting as a solitary colonic mass: two rare cases and a literature review Aims: Follicular dendritic cell (FDC) sarcoma is a rare neoplasm originating from follicular dendritic cells in germinal centres. It is classified as conventional and Epstein-Barr virus (EBV)-positive inflammatory FDC sarcoma according to the 2019 World Health Organization classification of digestive system tumours; the latter is rarer. So in view of the rarity and difficulty in diagnosis, the aim of the manuscript is to share our experience of diagnosing EBV-positive inflammatory FDC sarcoma. Methods and results: Here, we describe the clinicopathological features, gross description, histomorphology, immunophenotype, EBV-encoded mRNA (EBER) in-situ hybridisation, gene rearrangement and clinical follow-up of two patients with EBV-positive inflammatory FDC sarcoma in the colon, and review the relevant literature. The tumours were found in two males, aged 53 and 48 years, respectively, with a tumour diameter between 10 and 45 mm. Both cases occurred in the colon and presented as pedunculated colonic masses. Microscopically, scanty atypical ovoid to spindle neoplastic cells were mixed in a background of florid lymphoplasmacytic infiltration. The nuclei of these atypical cells showed vesicular chromatin and small, distinct nucleoli. Immunohistochemistry demonstrated that the atypical stromal cells were positive for CD21, CD23, CD35, and D2-40. EBER in-situ hybridisation also gave positive results in two cases. There was a mean follow-up of 9 months (range, 7-11 months). Conclusion: EBV-positive inflammatory FDC sarcoma is an extremely rare tumour with a distinct morphology and phenotype. Therefore, it is very important to recognise it particularly for correct diagnosis and prevention of misdiagnosis and mistreatment.

Background Definitive diagnosis of primary central nervous system lymphoma (PCNSL) requires invasive surgical brain biopsy, causing treatment delays. In this paper, we identified and validated tumor-specific markers that can distinguish PCNSL from other CNS tumors in tissues. In a pilot study, we tested these newly identified markers in plasma. Results The Methylation Outlier Detector program was used to identify markers in TCGA dataset of 48 diffuse large B-cell lymphoma (DLBCL) and 656 glioblastomas and lower-grade gliomas. Eight methylated markers clearly distinguished DLBCL from gliomas. Marker performance was verified (ROC-AUC of ≥ 0.989) in samples from several GEO datasets (95 PCNSL; 2112 other primary CNS tumors of 11 types). Next, we developed a novel, efficient assay called Tailed Amplicon Multiplexed-Methylation-Specific PCR (TAM-MSP), which uses two of the methylation markers, cg0504 and SCG3 triplexed with ACTB. FFPE tissue sections (25 cases each) of PCNSL and eight types of other primary CNS tumors were analyzed using TAM-MSP. TAM-MSP distinguished PCNSL from the other primary CNS tumors with 100% accuracy (AUC = 1.00, 95% CI 0.95–1.00, P < 0.001). The TAM-MSP assay also detected as few as 5 copies of fully methylated plasma DNA spiked into 0.5 ml of healthy plasma. In a pilot study of plasma from 15 PCNSL, 5 other CNS tumors and 6 healthy individuals, methylation in cg0504 and SCG3 was detectable in 3/15 PCNSL samples (20%). Conclusion The Methylation Outlier Detector program identified methylated markers that distinguish PCNSL from other CNS tumors with accuracy. The high level of accuracy achieved by these markers was validated in tissues by a novel method, TAM-MSP. These studies lay a strong foundation for a liquid biopsy-based test to detect PCNSL-specific circulating tumor DNA.

Background The tumour–stroma ratio (TSR) is identified as a promising prognostic parameter for breast cancer, but the cutoff TSR value is mostly assessed by visual assessment, which lacks objective measurement. The aims of this study were to optimize the cutoff TSR value, and evaluate its prognosis value in patients with breast cancer both as continuous and categorical variables. Methods Major clinicopathological and follow-up data were collected for a series of patients with breast cancer. Tissue microarray images stained with cytokeratin immunohistochemistry were evaluated by automated quantitative image analysis algorithms to assess TSR. The potential cutoff point for TSR was optimized using maximally selected rank statistics. The association between TSR and 5-year disease-free survival (5-DFS) was assessed by Cox regression analysis. Kaplan–Meier analysis and log-rank test were used to assess the significance in survival analysis. Results The optimal cut-off TSR value was 33.5%. Using this cut-off point, categorical variable analysis found that low TSR (i.e., high stroma, TSR ≤ 33.5%) predicts poor outcomes for 5-DFS (hazard ratio [HR] = 2.82, 95% confidence interval [CI] = 1.81–4.40, P = 0.000). When TSR was considered as a continuous parameter, results showed that increased stroma content was associated with worse 5-DFS (HR = 1.71, 95% CI = 1.34–2.18, P = 0.000). Similar results were also obtained in three molecular subtypes in continuous and categorical variable analyses. Moreover, in the Kaplan–Meier analysis, log-rank test showed that low TSR displayed a worse 5-DFS than high TSR (P = 0.000). Similar results were also obtained in patients with triple-negative breast cancer, human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and luminal–HER2-negative breast cancer. Conclusion TSR is an independent predictor for 5-DFS in breast cancer with worse survival outcomes in low TSR. The prognostic value of TSR was also observed in other three molecular subtypes.