SMARCB1-deficient malignant melanocytic uveal tumours: a new neural crest-derived tumour entity with SMARCB1-related germline predisposition.

Rhabdoid tumours (RT) are an aggressive malignancy affecting <2-year-old infants, characterised by biallelic loss-of-function alterations in SWI/SNF-related BAF chromatin remodelling complex subunit B1 (SMARCB1) in nearly all cases. Germline SMARCB1 alterations are found in ~30% of patients and define the RT Predisposition Syndrome type 1 (RTPS1). Uveal melanoma (UVM), the most common primary intraocular cancer in adults, does not harbour SMARCB1 alterations.

E-Cadherin Mutational Landscape and Outcomes in Breast Invasive Lobular Carcinoma.

Invasive lobular carcinomas (ILC) are characterized by the loss of E-cadherin expression and CDH1 gene inactivation. Diagnostic reproducibility for this tumor type is currently suboptimal and could be improved by a better understanding of its histomolecular and clinical heterogeneity. We have analyzed the relationship between the presence, type, or position of CDH1 mutations, E-cadherin expression, and clinicopathological features (including outcome) in a retrospective series of 251 primary ILC with a long follow-up (median: 9.

MDM4 amplification in atypical lipomatous tumors/well-differentiated liposarcoma: Private event or alternative oncogenic mechanism?

Adipocytic tumors are the most common mesenchymal tumors in soft tissues. Among them, a diagnostic challenge relies in the distinction between lipoma and atypical lipomatous tumor (ALT)/well differentiated liposarcoma (WDLPS), as both entities are often undistinguishable not only from a radiological point of view, but also at the microscopic level and particularly when dealing with small tumor specimen. Thus, detection of recurrent MDM2 amplifications may be the only criteria to discriminate malignant tumors from lipomas.

Breast carcinomas with osteoclast-like giant cells: a comprehensive clinico-pathological and molecular portrait and evidence of RANK-L expression.

Breast carcinomas (BC) with osteoclast-like giant cells (OGC) are rare. Despite their distinct stromal features, their molecular characteristics remain unknown. Here, we report comprehensive clinico-pathological and molecular findings for 27 patients diagnosed with BC-OGC at Institut Curie between 2000 and 2021.

Hemoglobin overexpression and splice signature as new features of inflammatory breast cancer?

Introduction: Inflammatory Breast Cancer (IBC) is the most aggressive form of breast carcinoma characterized by rapid onset of inflammatory signs and its molecular fingerprint has not yet been elucidated.

Objectives: The objective of this study was to detect both gene expression levels and alternate RNA splice variants specific for IBC.

Methods: W e performed splice-sensitive array profiling using Affymetrix Exon Array and quantitative RT-PCR analyses in 177 IBC compared to 183 non-IBC.

Disseminated Tumor Cells Predict Efficacy of Regional Nodal Irradiation in Early Stage Breast Cancer.

Purpose: Disseminated tumor cells (DTCs) collect in the bone marrow and indicate micrometastatic spread. We previously reported that DTCs could be a predictive factor for the efficacy of regional node irradiation (internal mammary nodes [IMNs]/supra- and infraclavicular nodes [SCNs]). In this article, we report the long-term results (>10 years) on the impact of DTC status in early stage breast cancer.

The iron chelator deferasirox synergises with chemotherapy to treat triple-negative breast cancers.

To ensure their high proliferation rate, tumor cells have an iron metabolic disorder causing them to have increased iron needs, making them more susceptible to iron deprivation. This vulnerability could be a therapeutic target. In breast cancers, the development of new therapeutic approaches is urgently needed for patients with triple-negative tumors, which frequently relapse after chemotherapy and suffer from a lack of targeted therapies.

[Internal quality control on HER2 status determination in breast cancers: Experience of a cancer center].

Introduction: The implementation of an internal quality control is mandatory to guarantee the accuracy of HER2 status in invasive breast cancers.

Objectives: To evaluate the impact of our quality control assurance on HER2 status results in invasive breast carcinomas from 2008 to 2014.

Methods: HER2 status was determined by immunohistochemistry as the first-line indication, completed by fluorescence in situ hybridization (FISH) for scores 2+ by immunohistochemistry.

Clinical value of R-spondins in triple-negative and metaplastic breast cancers.

Background: RSPO ligands, activators of the Wnt/β-catenin pathway, are overexpressed in different cancers. The objective of this study was to investigate the role of RSPOs in breast cancer (BC).

Methods: Expression of RSPO and markers of various cancer pathways were measured in breast tumours and cell lines by qRT-PCR.

Adult ocular medulloepithelioma diagnosed by transscleral fine needle aspiration: A case report.

Ocular medulloepithelioma (ME) is a rare congenital tumor which occurs usually during childhood but is also reported in adults. They have seen an intraocular tumor in an 89 years-old female with a history of small cell lung carcinoma. Transscleral fine needle aspiration was performed.

MED12 mutations in breast phyllodes tumors: evidence of temporal tumoral heterogeneity and identification of associated critical signaling pathways.

Exome sequencing has recently identified highly recurrent MED12 somatic mutations in fibroadenomas (FAs) and phyllodes tumors (PTs). In the present study, based on a large series, we confirmed the presence of MED12 exon 1 and 2 mutations in 49% (41/83) of PTs, 70% (7/10) of FAs and 9.1% (1/11) of fibromatoses.

Cytological features of NUT midline carcinoma arising in sino-nasal tract and parotid gland: Report of two new cases and review of the literature.

Nuclear Protein in Testis (NUT) Midline Carcinoma (NMC) represents a recently described, uncommon, high-grade and extremely lethal malignancy mainly occurring in children and young adults. Such tumors are genetically characterized by chromosomal rearrangements of the NUT gene. Cytological description of NUT carcinoma is limited and only seven cases were reported up to date.

Identification of new candidate therapeutic target genes in head and neck squamous cell carcinomas.

Background: We aimed at identifying druggable molecular alterations at the RNA level from untreated HNSCC patients, and assessing their prognostic significance.

Methods: We retrieved 96 HNSCC patients who underwent primary surgery. Real-time quantitative RT-PCR was used to analyze a panel of 42 genes coding for major druggable proteins.

Expression of ANRIL-Polycomb Complexes-CDKN2A/B/ARF Genes in Breast Tumors: Identification of a Two-Gene (EZH2/CBX7) Signature with Independent Prognostic Value.

Unlabelled: ANRIL, a long noncoding RNA (lncRNA), has recently been reported to have a direct role in recruiting polycomb repressive complexes PRC2 and PRC1 to regulate the expression of the p15/CDKN2B-p16/CDKN2A-p14/ARF gene cluster. Expression analysis of ANRIL, EZH2, SUZ12, EED, JARID2, CBX7, BMI1, p16, p15, and p14/ARF genes was evaluated in a large cohort of invasive breast carcinomas (IBC, n = 456) by qRT-PCR and immunohistochemistry (IHC) was performed on CBX7, EZH2, p14, p15, p16, H3K27me3, and H3K27ac. We observed significant overexpression in IBCs of ANRIL (19.

Estrogen-Receptor, Progesterone-Receptor and HER2 Status Determination in Invasive Breast Cancer. Concordance between Immuno-Histochemistry and MapQuant™ Microarray Based Assay.

Background: Hormone receptor status and HER2 status are of critical interest in determining the prognosis of breast cancer patients. Their status is routinely assessed by immunohistochemistry (IHC). However, it is subject to intra-laboratory and inter-laboratory variability.

Breast Cancer Cell-Derived GM-CSF Licenses Regulatory Th2 Induction by Plasmacytoid Predendritic Cells in Aggressive Disease Subtypes.

Reciprocal interactions between tumor cells and their microenvironment vitally impact tumor progression. In this study, we show that GM-CSF produced by primary breast tumor cells induced the activation of plasmacytoid predendritic cells (pDC), a cell type critical to anti-viral immunity. pDC that expressed the GM-CSF receptor were increased in breast tumors compared with noninvolved adjacent breast tissue.

Epigenomic alterations in breast carcinoma from primary tumor to locoregional recurrences.

Introduction: Epigenetic modifications such as aberrant DNA methylation has long been associated with tumorogenesis. Little is known, however, about how these modifications appear in cancer progression. Comparing the methylome of breast carcinomas and locoregional evolutions could shed light on this process.

Respective prognostic value of genomic grade and histological proliferation markers in early stage (pN0) breast carcinoma.

Background: Genomic grade (GG) is a 97-gene signature which improves the accuracy and prognostic value of histological grade (HG) in invasive breast carcinoma. Since most of the genes included in the GG are involved in cell proliferation, we performed a retrospective study to compare the prognostic value of GG, Mitotic Index and Ki67 score.

Methods: A series of 163 consecutive breast cancers was retained (pT1-2, pN0, pM0, 10-yr follow-up).

External validation of Adjuvant! Online breast cancer prognosis tool. Prioritising recommendations for improvement.

Background: Adjuvant! Online is a web-based application designed to provide 10 years survival probability of patients with breast cancer. Several predictors have not been assessed in the original Adjuvant! Online study. We provide the validation of Adjuvant! Online algorithm on two breast cancer datasets, and we determined whether the accuracy of Adjuvant! Online is improved with other well-known prognostic factors.

The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4.

HIPK2 is a eukaryotic Serine-Threonine kinase that controls cellular proliferation and survival in response to exogenous signals. Here, we show that the human transcription factor ZBTB4 is a new target of HIPK2. The two proteins interact in vitro, colocalize and associate in vivo, and HIPK2 phosphorylates several conserved residues of ZBTB4.

Lobular phenotype related to occult-metastatic spread in axillary sentinel node and/or bone marrow in breast carcinoma.

To determine whether any histological trait was associated with regional and/or systemic spread of occult tumour cells (OTCs) in small size invasive breast cancer, we compared tumour characteristics, axillary sentinel lymph node (SN) and bone marrow (BM) status in a series of 287 pT1T2 cases. Surgery was the first step of treatment, associated with SN procedure and with BM aspiration for the detection of OTC. SN was histologically classified as negative, metastatic (>2mm), micro-metastatic (>0.

Analysis of correlation between mitotic index, MIB1 score and S-phase fraction as proliferation markers in invasive breast carcinoma. Methodological aspects and prognostic value in a series of 257 cases.

Background: The study was designed in order to evaluate the degree of correlation of mitotic index (MI), Ki67 (MIB1) score and S-phase fraction (SPF) as markers of cell proliferation and prognosis in breast cancer.

Materials And Methods: The series analysed corresponded to 257 consecutive invasive breast carcinoma, treated at the Institut Curie, France, in 1995. Nottingham histological grade and MIB1 semiquantitative and quantitative score were assessed on histological sections, whereas SPF was calculated using flow cytometry analysis of fine-needle aspiration products.

HER2 status in patients with breast carcinoma is not modified selectively by preoperative chemotherapy and is stable during the metastatic process.

Background: The objective of this study was to determine whether HER2 expression levels in breast carcinomas were modified by chemotherapy or during the metastatic process.

Methods: HER2 expression was analyzed on sequential tissue specimens taken from the primary tumor before patients received preoperative chemotherapy (CT) and from post-CT residual breast tumor or at a metastatic site. The first group of patients included 59 women who presented with T2-T4,N1-N2 breast carcinoma and were treated by preoperative anthracycline-based CT and then underwent surgery.