To conduct genetic linkage analysis in order to localize predisposition genes for hereditary prostate cancer (CaP), as various epidemiological studies have demonstrated a family aggregation in 15 to 25% of cases, and the development of hereditary forms in 5 to 10% of cases of CaP.

(1) To determine the frequency of familial (at least 2 cases) and hereditary forms of prostate cancer (CaP), (2) to define the results according to the patient's age at diagnosis, as various epidemiological studies have demonstrated a possible familial aggregation of CaP in about 15 to 25% of cases. Carter's familial segregation study (P.N.A.S. 1992, 89, 3367-71) showed that a genetic predisposition, with autosomal dominant transmission, could be responsible for 9% of all cases of prostate cancer.

The renal medullary carcinoma is a rare tumor. We report a case in a black patient with sickle cell trait. The tumor was located in the lower pole of the left kidney. It had a tubular and microcystic architecture. It was composed of large eosinophilic cells with vesicular nuclei containing prominent nucleoli, in a desmoplastic and inflammatory stroma. By immunohistochemistry, the tumoral cells were positive for cytokeratin and Ulex europaeus lectin. Electron microscopy revealed small intracytoplasmic lumina with microvilli. The flow cytometric study showed DNA-multiploidy. The cytogenetic study revealed tetraploidy without structural abnormality. The renal medullary carcinoma is often reported in young black patients with sickle cell trait. Its microscopic, immunohistochemical and ultrastructural features favor its identification as a particular variety of Bellini duct carcinoma. Its link with sickle cell trait has to be defined.

In renal cell carcinoma, bone metastases remain a major medical challenge because they are refractory to the antiproliferative effects of immunotherapy. We critically review the biological and clinical data which implicate interleukin-6 in the tumor growth, the pathogenesis of the bone metastases and the response to immunotherapy.

The Muir-Torre syndrome is an autosomal dominant hereditary condition predisposing to cancer. It is characterized by skin tumors associated with adenocarcinoma of the colon or other neoplasias observed in the context of hereditary non-polyposis colorectal cancer (HNPCC). The Muir-Torre syndrome is also characterized by the frequent presence of multiple colonic polyps and the relatively moderate aggressivity of the tumors.

The Muir-Torre Syndrome is a rare genodermatosis, defined by the occurrence of cutaneous tumors (such as sebaceous adenomas, epitheliomas, or carcinomas, and/or keratoacanthomas), and internal malignancies. Recently, molecular analysis in hereditary non polyposis colorectal cancer demonstrated a common genetic basis, linking these two disorders, with the observation of germline mutations in the hMSH2 gene (one of the DNA mismatch repair system genes) in both syndromes. Such molecular demonstration of a single nosological entity should be clinically used to improve the indications of molecular testings in oncogenetics, still restricted to highly stringent criteria for hereditary non polyposis colorectal cancer.

Inflammatory response involves complex signalling pathways at cellular and molecular levels. During the cellular activation, intracellular substrates are subsequently phosphorylated for inducing transcription and synthesis of various inflammatory and/or anti-inflammatory mediators. This review focuses on the description of the main mechanisms involved in the activation signalling pathways that occur during inflammatory processes.

Anaplastic large-cell lymphomas were recognized by Stein in 1985. Less than fifteen years were necessary to confirm this entity, as well as her phenotype and to characterize the t(2;5) (p23;q35) chromosomal abnormality. This rare subgroup of non-Hodgkin's lymphomas (15% of peripheral T cell lymphomas and 8% of all diffuse aggressive lymphomas) is individualized in the Real classification. This disease, which had a bimodal age distribution, is clinically characterized by a diffuse nodal involvement and the frequency of extranodal involvement, especially skin and lungs. Primitive cutaneous anaplastic large cell lymphomas belong to the cutaneous CD30+ lymphoproliferative diseases spectrum. Among peripheral T cell and diffuse aggressive lymphomas, they have the better prognosis. We present in this paper a review of the recent advances in the knowledge, treatment and prognosis of this peculiar entity.

The normal hair development requires WNT signalling pathways. A constitutive activation of beta-catenin, one of the components of this cascade, induces an abnormal proliferation of hair matrix cells. This activation is observed in a human skin tumours called pilomatricoma. Mutations of the beta-catenin gene are detected in 75% of the tumours analysed.

Brooke-Spiegler syndrome is an association of multiple trichoepitheliomas and cylindromas, sometimes accompanied by other adnexal tumors.

The recent identification of the BRCA1 and BRCA2 genes allows to understand in an increasing number of cases the origin of a breast/ovarian cancer family history and thereby to propose genetic testing to at risk women. However to know to be carrier of a predisposing germline mutation is at the present to deal with the difficult choice of different supportive cares: close follow up or prophylactic surgery. Numerous studies still have to be done to determine the better management of women at risk. The other challenges are the understanding of the origin of each breast or ovarian cancer case; to identify the factors which modify the tumor risks in predisposed women; and finally to win the social acceptance of genetic testing avoiding any discrimination.

As part of a clinical research project, proliferative parameters were studied in primary breast cancer: standardization and technical validation of thymidine kinase (TK), thymidylate synthase (TS) and protein tyrosine kinase (PTK) are described. A total of 633 frozen tumor specimens, available in four institutions, was analyzed in three flow cytometry laboratories for DNA content and percentage of S-phase cells (%S) measurement. 1) The standardization step consisted in developing a common protocol for sample preparation; then, common cell suspensions were analyzed in order to perform an inter-laboratory control. Objective guidelines were elaborated to interpret DNA histograms in breast carcinoma. 2) DNA-aneuploidy was observed in 61% of cases of the retrospective series. Compared with DNA-aneuploid tumors, mean %S was significantly lower in case of DNA-diploidy (respectively: 6.4% and 2.2%, p < 0.001). When compared between the four institutions, %S distributions did not differ significantly. 3) %S is strongly correlated with TK, TS and PTK and high percentages were also observed in high grade tumors or tumor without hormone receptors. These results show that a standardization in using flow cytometers and DNA software allows multicenter studies.

Prostate cancer is an androgen-dependent tumor which presents an androgen-independent regrowth after clinical regression in response to antiandrogen treatment. Four hypotheses have been developed to understand how androgen signal transduction pathway mediate androgen-independent tumor progression: over expression of the wild-type androgen-receptor gene, androgen-receptor gene mutation, excessive recruitment of transcriptional co-activator ARA-70 and a cross-talk between the androgen-receptor and the growth factor receptor pathways. In this work, C. Sawyers's group elegantly demonstrates, in LAPC-4 androgen-independent prostate cancer sublines, that forced hyperexpression of HER-2/Neu receptor tyrosine kinase allowed androgen-independent growth, that HER-2/Neu activated the androgen-receptor pathway in the absence of androgens and synergized with low levels of androgen to superactivate the pathway. These important data could have therapeutic implications for the management of androgen-independent prostate cancer.