BMC Cancer

The CYP19A1 gene, which encodes the enzyme responsible for androgen aromatization into estrogens, may play an important role in breast cancer aggressiveness. However, no study has evaluated CYP19A1 gene expression in the peripheral blood of women with relapsed breast cancer. In this cross-sectional study, CYP19A1 gene expression was quantified by RT-PCR in the peripheral blood of 146 women with breast cancer who were first divided into two groups according to the expression of CYP19A1 (low and high); each group had 73 patients. Subsequently, women were divided into two groups: those without recurrence (control, n = 85) and those with recurrence (study, n = 61). Statistical analysis of the data was performed using ANOVA, the Mann-Whitney, Chi-square or Fisher’s exact test (p <  0.05). There were no significant differences between the relative expression of CYP19A1 mRNA in the low expression group and the high expression group according to the variables studied. There were no significant differences in CYP19A1 gene expression in the study and control groups (p = 0.8461). In the relapse group, CYP19A1 gene expression was significantly higher in the hybrid luminal subtype than in the triple-negative subtype (p = 0.0321), whereas it was significantly lower in HER2-negative cases than in HER2-positive cases (p <  0.0376). Women with locoregional recurrence showed higher expression than women with distant recurrence (p <  0.0001). The present study found no significant differences between women with high and low expression of the CYP19A1 gene mRNA or between those in the study group and the control group. However, in women with recurrence, there was increased expression of CYP19A1 mRNA in those who had the luminal hybrid subtype and locoregional relapse and decreased expression in those negative for HER2.

Olaratumab is a platelet-derived growth factor receptor-α (PDGFRα)-targeting monoclonal antibody blocking PDGFRα signaling. PDGFRα expression is associated with a more aggressive phenotype and poor ovarian cancer outcomes. This randomized, open label phase II study evaluated olaratumab plus liposomal doxorubicin compared with liposomal doxorubicin alone in advanced ovarian cancer patients. Patients with platinum-refractory or platinum-resistant advanced ovarian cancer were randomized 1:1 to receive liposomal doxorubicin (40 mg/m2, intravenous infusion) administered every 4 weeks with or without olaratumab (20 mg/kg, IV infusion) every 2 weeks. Patients were stratified based on prior response to platinum therapy (refractory vs resistant). The primary efficacy endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, duration of response, and safety. A total of 123 patients were treated (62 olaratumab+liposomal doxorubicin; 61 liposomal doxorubicin). Median PFS was 4.2 months for olaratumab+liposomal doxorubicin and 4.0 months for liposomal doxorubicin (stratified hazard ratio [HR] = 1.043; 95% confidence interval [CI] 0.698–1.558; p = 0.837). Median OS was 16.6 months and 16.2 months in the olaratumab+liposomal doxorubicin and liposomal doxorubicin arms, respectively (HR = 1.098; 95% CI 0.71–1.71). In the platinum-refractory subgroup, median PFS was 5.5 months (95% CI 1.6–9.2) and 3.7 months (95% CI 1.9–9.2) in the olaratumab+liposomal doxorubicin (n = 15) and liposomal doxorubicin arms (n = 16), respectively (HR = 0.85; 95% CI 0.38–1.91). Overall, 59.7% (olaratumab+liposomal doxorubicin) and 65.6% (liposomal doxorubicin) of patients reported grade ≥ 3 adverse events regardless of causality. The most common treatment-emergent adverse events (all grades) regardless of causality were fatigue related (61%), nausea (57%), and constipation (52%) with olaratumab+liposomal doxorubicin and nausea (64%), fatigue related (62%), and mucositis (46%) with liposomal doxorubicin. The addition of olaratumab to liposomal doxorubicin did not result in significant prolongation of PFS or OS in platinum-resistant or platinum-refractory ovarian cancer. ClinicalTrials.gov identifier: NCT00913835 ; registered June 2, 2009.

Bladder leiomyosarcoma is the most frequent mesenchymal neoplasm of the bladder. However, the rarity of the disease and some morphological aspects could give serious problems to differential diagnosis. A 86-year-old male patient was referred to our institution to undergo endoscopic low-urinary-tract re-evaluation 2 months after the detection of a “low-grade urothelial neoplasia” in urinary cytology. A TURBT (transurethral resection of bladder tumor) was performed and revealed a tumor extending for 3.5 cm with thin stalk peduncle on the left lateral wall of the bladder, cephalad and lateral to the left ureteral orifice. The exophytic part of the tumor was resected with the underlying bladder wall. Histologically, the tumor showed a quite complex pattern, composed of spindle cells, with often invasion to the surrounding bladder muscular wall, and the presence of numerous multinucleated, osteoclast-like giant cells, scattered throughout the neoplasia. Here we report a unique case of urinary bladder leiomyosarcoma with osteoclast-like multinucleated giant cells (OGCs). These cells, confounding the morphological aspect, indeed showed an immunohistochemical phenotype of non-neoplastic origin (most likely a histiocyte/macrophage differentiation). We feel that the presence of the OGCs within this tumor is reactive. Nevertheless, more research is necessary to understand the role of OGCs in urinary bladder tumors and leiomyosarcoma, in paticular.

Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6–8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).

The differentiation of pancreatic ductal adenocarcinoma (PDAC) could be associated with prognosis and may influence the choices of clinical management. No applicable methods could reliably predict the tumor differentiation preoperatively. Thus, the aim of this study was to compare the metabonomic profiling of pancreatic ductal adenocarcinoma with different differentiations and assess the feasibility of predicting tumor differentiations through metabonomic strategy based on nuclear magnetic resonance spectroscopy. By implanting pancreatic cancer cell strains Panc-1, Bxpc-3 and SW1990 in nude mice in situ, we successfully established the orthotopic xenograft models of PDAC with different differentiations. The metabonomic profiling of serum from different PDAC was achieved and analyzed by using 1H nuclear magnetic resonance (NMR) spectroscopy combined with the multivariate statistical analysis. Then, the differential metabolites acquired were used for enrichment analysis of metabolic pathways to get a deep insight. An obvious metabonomic difference was demonstrated between all groups and the pattern recognition models were established successfully. The higher concentrations of amino acids, glycolytic and glutaminolytic participators in SW1990 and choline-contain metabolites in Panc-1 relative to other PDAC cells were demonstrated, which may be served as potential indicators for tumor differentiation. The metabolic pathways and differential metabolites identified in current study may be associated with specific pathways such as serine-glycine-one-carbon and glutaminolytic pathways, which can regulate tumorous proliferation and epigenetic regulation. The NMR-based metabonomic strategy may be served as a non-invasive detection method for predicting tumor differentiation preoperatively.

Invasive cervical cancer (ICC) is caused by high-risk human papillomavirus types (HR-HPVs) and is usually preceded by a long phase of intraepithelial neoplasia (CIN). Before invasion, (epi) genetic changes, potentially applicable as molecular markers within cervical screening, occur in HPV host cells. Epigenetic alterations, such as dysregulation of microRNA (miRNA) expression, are frequently observed in ICC. The mechanisms and role of miRNA dysregulation in cervical carcinogenesis are still largely unknown. We provide an overview of the studies investigating miRNA expression in relation to ICC progression, highlighting their common outcomes and their weaknesses/strengths. To achieve this, we systematically searched through Pubmed database all articles between January 2010 and December 2017. From the 24 studies retrieved, miR-29a and miR-21 are the most frequently down- and up-regulated in ICC progression, respectively. Microarray-based studies show a small overlap, with miR-10a, miR-20b, miR-9, miR-16 and miR-106 found repeatedly dysregulated. miR-34a, miR-125 and miR-375 were also found dysregulated in cervical exfoliated cells in relation to cancer progression. The pivotal role of miRNAs in ICC progression and initial development is becoming more and more relevant. Available studies are essentially based on convenience material, entailing possible selection bias, and frequently of small size: all these points still represent a limitation to a wide comprehension of miRNAs relevant for ICC. The targeted approach instead of a genome-wide investigation still precludes the identification of all the relevant miRNAs in the process. The implementation of deep sequencing on large scale population-based studies will help to discover and validate the relation between altered miRNA expression and CC progression for the identification of biomarkers. Optimally, once explored on a miRNome scale, small specific miRNA signatures maybe used in the context of screening.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/1471-2407-11-527.

The relapse rate in early stage non-small cell lung cancer (NSCLC) after surgical resection is high. Prognostic biomarkers may help identify patients who may benefit from additional therapy. The Helicase-like Transcription Factor (HLTF) is a tumor suppressor, altered in cancer either by gene hypermethylation or mRNA alternative splicing. This study assessed the expression and the clinical relevance of wild-type (WT) and variant forms of HLTF RNAs in NSCLC. We analyzed online databases (TCGA, COSMIC) for HLTF alterations in NSCLC and assessed WT and spliced HLTF mRNAs expression by RT-ddPCR in 39 lung cancer cell lines and 171 patients with resected stage I-II NSCLC. In silico analyses identified HLTF gene alterations more frequently in lung squamous cell carcinoma than in adenocarcinoma. In cell lines and in patients, WT and I21R HLTF mRNAs were detected, but the latter at lower level. The subgroup of 25 patients presenting a combined low WT HLTF expression and a high I21R HLTF expression had a significantly worse disease-free survival than the other 146 patients in univariate (HR 1.96, CI 1.17–3.30; p = 0.011) and multivariate analyses (HR 1.98, CI 1.15–3.40; p = 0.014). A low WT HLTF expression with a high I21R HLTF expression is associated with a poor DFS.