Malignant phyllodes tumor is a rare breast tumor, with distant metastases and heterologous differentiation in a few cases. We report a case of malignant phyllodes tumor with liposarcomatous differentiation in the primary tumor and osteosarcomatous differentiation in the lung metastatic tumor. A middle-aged female presented with a well-defined mass in the upper lobe of the right lung measuring 5.0 × 5.0 × 3.0 cm. The patient had a history of malignant phyllodes tumor in the breast. The patient underwent a right superior lobectomy. Histologically, the primary tumor was a typical malignant phyllodes tumor with pleomorphic liposarcomatous differentiation, while the lung metastasis showed osteosarcomatous differentiation without original biphasic features. The phyllodes tumor and heterologous components showed CD10 and p53 expression, and were negative for ER, PR, and CD34. Exome sequencing revealed TP53, TERT, EGFR, RARA, RB1, and GNAS mutations in all three components. Although the lung metastasis were morphologically different from the primary breast tumor, their common origin was demonstrated through immunohistochemical and molecular characterization. Cancer stem cells give rise to tumor heterogeneous cells, and heterologous components in malignant phyllodes tumors may indicate unfavorable prognosis and a greater risk of early recurrence and metastasis.

Cell adhesion to neighboring cells is a fundamental biological process in multicellular organisms that is required for tissue morphogenesis. A tight coordination between cell-cell adhesion, signaling, and gene expression is a characteristic feature of normal tissues. Changes, and often disruption of this coordination, are common during invasive and metastatic cancer development. The Wnt/β-catenin signaling pathway is an excellent model for studying the role of adhesion-mediated signaling in colorectal cancer (CRC) invasion and metastasis, because β-catenin has a dual role in the cell; it is a major adhesion linker of cadherin transmembrane receptors to the cytoskeleton and, in addition, it is also a key transducer of Wnt signaling to the nucleus, where it acts as a co-transcriptional activator of Wnt target genes. Hyperactivation of Wnt/β-catenin signaling is a common feature in the majority of CRC patients. We found that the neural cell adhesion receptor L1CAM (L1) is a target gene of β-catenin signaling and is induced in carcinoma cells of CRC patients, where it plays an important role in CRC metastasis. In this review, we will discuss studies on β-catenin target genes activated during CRC development (in particular, L1), the signaling pathways affected by L1, and the role of downstream target genes activated by L1 overexpression, especially those that are also part of the intestinal stem cell gene signature. As intestinal stem cells are highly regulated by Wnt signaling and are believed to also play major roles in CRC progression, unravelling the mechanisms underlying the regulation of these genes will shed light on both normal intestinal homeostasis and the development of invasive and metastatic CRC.

Molecular phenotype discordance between primary and metastatic tumors exists in a small proportion of breast cancer (BC) patients with accessible synchronous metastases. Reduced therapeutic effect and delays in treatment can occur when decisions on systemic therapy are determined by ignoring the differences in tumor type. Here we report a 54-year-old post-menopausal locally advanced BC patient, who showed no tumor response following routine treatment which included targeting anti-HER2, based on the phenotype of primary tumor (Luminal B, HER2-positive), during neoadjuvant therapy. However, following a secondary biopsy of the metastatic subclavian lymph node, a distinct pathological feature (Triple-negative) was revealed; chemotherapy was adjusted accordingly and resulted in a positive tumor response. Various subclones within primary and metastatic lesions were identified which might be attributed to tumor heterogeneity and in turn resulting in the phenotypic discordance in the receptor status. The patient died due to tumor progression related to triple-negative-featured lung metastasis, with overall survival time of 26.4 months. This study strengthens the value of concurrent biopsies of both primary and synchronous metastatic lesions in BC patients, and provides a reference for treating this kind of tumor when discordance in the molecular phenotype is observed.

Background: Inflammatory myofibroblast tumor (IMT) is a rare tumor with obscure etiopathogenesis in which different inflammatory cells and myofibroblastic spindle cells are seen histologically. Although the majority of these neoplasms have a benign clinical course, the malignant form has also been reported. The gold standard is surgical treatment for complete removal. Our report describes a 50-year-old woman who underwent surgery for IMT of the lung. The aim is to determine whether cancer stem cells may be present in IMT of the lung. Methods: In April 2018, the patient underwent surgery for tumor mass asportation through lateral thoracotomy. The histology of the tumor was consistent with IMT of the lung. The ALDEFLUOR assay, after tissue digestion, was used to identify and sort human lung cancer cells expressing high and low aldehyde dehydrogenase (ALDH) activity. SOX2, NANOG, OCT-4, and c-MYC positivity were additionally determined by immunohistochemistry. Results: The specimen contained 1.10% ALDHhigh cells among all viable lung cancer cells, which indicates the population of cancer stem cells is not negligible. Immunohistochemically assessed cell positivity for ALDH1A1, SOX2, NANOG, OCT-4, and c-MYC, which are considered as lung cancer stem-like cells markers. Conclusion: For the first time, we demonstrated the presence of cancer stem cells in a case of IMT of the lung. This finding may provide a base for considering new pathological and molecular aspects of this tumor. This perspective suggests further studies to understand the possibility of developing recurrence depending on the presence of cancer stem cells.

The design and the preparation of a small library of 1,4-diphenyl-1,2,3-triazole derivatives is reported, with the aim to obtain a new class of Hedgehog pathway inhibitors. The smoothened protein is part of the hedgehog signaling pathway that is inhibited by the lead compound Vismodegib. Based on molecular modeling simulations, seven triazole derivatives of Vismodegib are synthesized and their biological effect on different endothelial, cancer, and cancer stem cell lines is reported.

Stem cells are undifferentiated cells that have the unique ability to self-renew and differentiate into many different cell types. Their function is controlled by core gene networks whose misregulation can result in aberrant stem cell function and defects of regeneration or neoplasia. HOX genes are master regulators of cell identity and cell fate during embryonic development. They play a crucial role in embryonic stem cell differentiation into specific lineages and their expression is maintained in adult stem cells along differentiation hierarchies. Aberrant HOX gene expression is found in several cancers where they can function as either oncogenes by sustaining cell proliferation or tumor-suppressor genes by controlling cell differentiation. Emerging evidence shows that abnormal expression of HOX genes is involved in the transformation of adult stem cells into cancer stem cells. Cancer stem cells have been identified in most malignancies and proved to be responsible for cancer initiation, recurrence, and metastasis. In this review, we consider the role of HOX genes in normal and cancer stem cells and discuss how the modulation of HOX gene function could lead to the development of novel therapeutic strategies that target cancer stem cells to halt tumor initiation, progression, and resistance to treatment.

BACKGROUND: Malignant meningiomas are rare neoplasms of the central nervous system that occur de novo or rarely as a result of transformation. They have a higher rate of recurrence and metastasis accompanied by a significantly shorter survivorship compared with benign variants. Meningioma cancer stem cells (CSCs) have been previously shown to be associated with resistance and aggressiveness. However, the role they play in meningioma progression is still being investigated.
METHODS: We report a 29-year-old man who underwent a resection of a grade I meningioma in 2011. The patient had multiple local recurrences of the tumor that showed an aggressive change in behavior and transformation to grade III meningioma, and developed extracranial metastasis to the cervical spine. He underwent multiple operations and received radiotherapy. Analysis of the tissues indicated the presence of CSC markers before metastasis, and showed increased expressions of associated markers in the metastasized tissue. In addition, similar to the patient\'s profile, the pharmacological testing of a primary cell line retrieved from the metastasized tissues showed a high level of drug tolerance and a diminished ability to initiate apoptosis.
CONCLUSIONS: Malignant progression of grade I meningioma can occur, and its eventuality may be anticipated by detecting CSCs. We performed a comprehensive literature review of relevant cases and discussed the clinical, diagnostic, and management characteristics of the reported cases.

Putative cancer stem cell (CSC) markers have arisen from melanoma mouse and in vitro models, but their expression in paraffin embedded patient samples relative to clinical outcome remains largely unexplored. Rather than cells of the tumour bulk, conceivably, CSC drive tumour progression. Accordingly, complete eradication may prevent melanoma relapse. Because elevated tumour-cell proliferation is an established indicator of aggressive disease, this study aimed to investigate the correlation between melanoma recurrence and proliferation of putative CSC that express CD271, CD166, or CD20. Additionally, the expression of these markers was studied in naevi, melanomas, and their recurrence. In melanoma patients, 30 with relapse (cases) and 30 without (controls) were matched for tumour thickness, ulceration, Clark level, subtype, site, gender, and age. One paraffin-embedded section of the patients\' primary melanoma (n = 60), relapse (n = 21), and naevus (n = 17) were immunohistochemically double-stained for Ki-67/MART1 and single-stained for CD271, CD166, and CD20. Their whole slide images were aligned as virtual quadruple stains. Image analysis established proliferation indices of each putative stem cell marker and the tumour bulk in addition to the markers\' percentage level in tumour areas and the epidermis. In cases vs controls, median dermal proliferation indices (no./mm2) were 211 vs 103 (p = 0.04) for CD271, 512 vs 227 (p = 0.3) for CD166, 184 vs 97 (p = 0.3) for CD20, and 95 vs 103 (p = 0.6) for the tumour bulk. Of additional interest, epidermal CD271+ keratinocytes totalled 8.8% in naevi and 0.98% in melanomas (p = 0.0007). Even though differences between naevi and melanomas also were observed for CD166 in both the epidermis (p = 0.002) and dermis (p = 0.006), they were visually less apparent. CD20+MART1+ cells were absent in half of the melanomas, and all naevi and relapses. In conclusion, high levels of CD271+Ki-67+MART1+ cells were linked to melanoma relapse as opposed to common Ki-67 indices in this particular case-control study. With further investigation, such cells could be potential targets of therapy. Especially, loss of epidermal CD271+ keratinocytes seemed necessary for melanoma development; hence, identification may serve as a diagnostic tool with additional research.

Cancer stem cells in breast cancer migrating to the bone marrow may cause future metastasis, particularly during periods of decreased immunity. Natural killer (NK) cells have a role in immune surveillance and are able to target cancer stem cells. The present study reported a case in which NK cell-based autologous immune enhancement therapy was used combined with conventional treatments in a patient with stage IIIA breast cancer, yielding >28 months of disease-free survival. However, there was a gradual decline in the in vitro expansion of NK cells with subsequent chemotherapeutic treatments. As this NK cell decline following chemotherapy may contribute to cancer cell immune evasion and future metastasis; modifying current cancer therapies in order to avoid potentially compromising the immune system may lead to improved treatment outcomes.

Glioblastoma is the most common and aggressive adult brain tumour. Over the last 10 years it has emerged that the subventricular zone (SVZ), the largest adult neural stem cell niche, has an important role in the disease. Converging evidence has implicated transformation of adult neural stems in gliomagenesis and the permissive stem cell niche in disease recurrence. Concurrently, clinical studies have suggested that SVZ involvement is a negative prognostic marker. It would follow that irradiating the SVZ may improve outcomes in glioblastoma by directly targeting this putative sanctuary site. To investigate this potential strategy, 11 retrospective studies and 1 prospective study examined the relationship between dose to the SVZ and survival outcomes in glioblastoma patients. This review summarises the theoretical underpinning of this strategy, provides a critical evaluation of the existing evidence and discusses the rationale for a clinical trial.