Multiple myeloma (MM) is a still incurable adult's severe hematologic malignancy. It is characterized by deregulation of several cytokines and their receptors. Among these cytokines, Insulin growth factor 1 (IGF1) and its receptor (IGF1-R) are well documented as major factor of malignant plasma cells growth and survival in multiple myeloma. The objective of this study was to analyze the expression of IGF1-R in multiple myeloma at diagnosis in correlation with clinical and biological data. IGF1-R gene plasma cells expression was studied in 47 patients and 17 controls by Taqman technology RT-PCR. IGF1-R gene was down expressed in the malignant plasma cells of MM patients at diagnosis compared to normal plasma cells, isolated from healthy donors (p = 0.01). Expression decrease was accentuated in the disease advanced stage IIIB. A negative correlation was found between IGF1-R malignant plasma cells expression and the percentage of bone marrow invasion (p = 0.03). Bone marrow infiltration greater than 30% was significantly associated with a low level of IGF1-R gene expression (p = 0.04). Our results suggest that the decreased expression of IGF1-R by malignant plasma cells is a prognostic factor associated with severe disease. Understanding of mechanisms involved in IGF1-R expression negative regulation may contribute to the discovery of new targets therapy in myeloma. the discovery of new targets therapy in myeloma.

A 61-year-old man, with a tuberous sclerosis, experienced severe acute reactions during a concomitant chemoradiotherapy regimen after 22Gy and one cycle of 5-fluorouracil-cisplatinum. He was treated for a cervical squamous cell lymph node of unknown origin. Grade 3 mucitis and epitheliitis were observed only in the irradiated fields and required the end of the radiotherapy. Tuberous sclerosis is characterized by a loss of the TSC2 function, with a permanent activation of the mTOR pathway. Logically, some kind of "radioresistance" should be observed. Increased radiosensitivity is paradoxical. This case illustrates how radiosensitivity is a complex phenomenon and clinically unpredictable. Efficiency of the protocols associations of mTOR inhibitors and radiotherapy should be carefully scrutinized.

The occurrence of abnormally pigmented skin lesions is a common phenomenon and often associated with the influence of ultraviolet radiation (UV) and other sources of DNA damage. Pigmentary lesions induced by UV radiation and other sources of DNA damage occur in healthy individuals, but human diseases with defective DNA repair represent important models which allow the investigation of possible underlying molecular mechanisms leading to hypo- and hyperpigmentations. There are several hereditary diseases which are known to go along with genetic defects of DNA repair mechanisms comprising Xeroderma pigmentosum (XP), Cockayne syndrome (CS), Trichothiodystrophy (TTD), Werner syndrome (WS), Bloom syndrome (BS), Fanconi anemia (FA) and Ataxia telangiectasia (AT). These diseases share clinical characteristics including poikilodermatic skin changes such as hypo-and hyperpigmentation. Since UV radiation is the most common source of DNA damage which can cause pigmentary lesions both in healthy individuals and in patients with genetic deficiency in DNA repair, in the present article, we focus on pigmentary lesions in patients with XP as an example of a disease associated with genetic defects in DNA repair.

The choice of salvage therapy for patients presenting relapsed chronic lymphocytic leukemia (CLL) has to take into account some factors influencing tumor resistance and comorbidities. Since 2010, new drugs targeting the tumor cells' signaling have been proposed for CLL patients. Waiting the results of various clinical trials evaluating these treatments, there is a need to describe the state-of-the-art concerning approved treatments such as chemotherapy and monoclonal antibodies.

The broncopulmonary cancer is a major problem of public health whose diagnosis is most of the time unfavorable. For a long time, strategies of management of cancer have not taken into consideration much the histological type and few authors have studied the implication of histological type of cancer on the future of patients having cancer.

Some of the main applications of molecular techniques using cellular materials obtained from tumors by means of non-gynecological exfoliative cytology or fine-needle aspiration are briefly described in this review.

The search for biological and clinical significance of equivocal urinary cytology has emerged as the most promising application of fluorescence in situ hybridization (FISH). Using the multiprobe UroVysion(®) assay, a negative FISH result in the presence of atypical urothelial cells favors the presence of reactive, benign alterations and helps to avoid unnecessary invasive procedures. However, a negative FISH result in case of a negative or equivocal cytology does not exclude low-grade urothelial neoplasia. Equivocal findings are a notorious problem after conservative treatment, particularly after BCG immunotherapy of carcinoma in situ, where even benign reactive changes can appear worrisome. In this situation, a positive FISH result in spite of non-high grade cytology independently indicates persistent or recurrent urothelial carcinoma. However, chromosomal abnormalities are not restricted to malignancy but may also occur in benign cells. Tetraploidy with a balanced duplication of the whole genome, or polyploidy can occur in non-neoplastic conditions of the bladder such as Decoy cells, radiotherapy-induced changes and urolithiasis. Thus, a positive FISH result in a patient with a history of pelvic irradiation does not prove cancer unless there is unequivocal 9p21 deletion. Recent studies show that an aggressive workup of patients with a suspicious cytology+positive UroVysion(®) result and negative cystoscopy is not currently justified. However, multi-target UroVysion(®) FISH remains an excellent tool to improve diagnosis in urinary cytopathology, provided that FISH results are interpreted in the light of the clinical situation, and that one reminds that FISH adds no diagnostic value in case of clearly positive, high-grade cytology.

Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research.

The SWI/SNF complex is a multiprotein complex essential for chromatin remodelling. As such, it plays a key role in the epigenetic regulation of genome expression. This complex is composed of a dozen of proteins, some of which are constant and ubiquitous, especially SMARCB1 and SMARCA4. Mutations in these genes are now described in an increasing number of tumors. Mutations in SMARCB1 characterize the majority of rhabdoid tumors, an aggressive malignancy that exquisitely depends on this single genetic event. Rare rhabdoid tumors have mutation in SMARCA4, a genetic abnormality also found in some medulloblastomas. Many other tumor types, of variable aggressiveness, show an abnormal loss of expression of SMARCB1, but the genetic underlying cause most often remains elusive. The recent sequencings of whole exomes have described frequent mutations in other genes of the SWI/SNF complex: mutations in ARID1A in liver, gastric or bladder carcinomas, and PBRM1 mutations in renal cancers. These data establish the wide role of SWI/SNF complex in cancers and justify that major efforts should now be devoted to this common mechanism of human oncogenesis.

Cancer is a known risk factor for the development of venous thromboembolism (VTE) and in particular, adenocarcinoma of the lung is known to be associated with a higher risk of thromboembolic event. EGFR activating mutations are more frequently found in this histological subtype than in other lung cancers. We report three cases of VTE in patients with adenocarcinoma of the lung and EGFR activating mutation. Our reported case series is atypical because the VTE event occurred early in the adenocarcinoma history: either leading to the diagnosis of cancer, or appearing very early in the management of the neoplasm.

Angiokeratomas are papular telangiectasias having a common histology of ectasia of the superficial dermal vessels surmounted by a hyperkeratotic epidermis.

Ovarian cancer is the most lethal of the gynaecological malignancies because this «silent killer» is almost always diagnosed at an advanced stage. Precursor lesions have at least been discovered. This review will describe in details specific features of tubal and ovarian preinvasive lesions and the old and novel techniques that could be used for early detection of ovarian cancer.

In the last 10 years, a number of important European randomized published studies investigated the optimal management of rectal cancer. In order to define an evidence-based approach of the clinical practice based, an international consensus conference was organized in Italy under the endorsement of European Society of Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO) and European Society of Therapeutic Radiation Oncology (ESTRO). The aim of this article is to present highlights of multidisciplinary rectal cancer management and to compare the conclusions of the international conference on 'Multidisciplinary Rectal Cancer Treatment: looking for an European Consensus' (EURECA-CC2) with the new National Comprehensive Cancer Network (NCCN) guidelines.