Hereditary persistence of alpha-fetoprotein is a rare disorder which exists with no simultaneous disease. The tenth case in the world (two brothers with seminoma and their father) is documented and a complete literature review was done.

To compare flow cytometric data (ploidy and proliferative activity or percentage SG2M-phase cells) to cytologic and histologic data of the bladder carcinomas.

Chromosomic aberrations play a major role in the initiation and the progression of benign as well as malignant tumors. In particular, trisomy 12 is frequently observed in female genitourinary tract tumors and constitutes a recurrent and often unique anomaly in stromal ovarian tumors such as fibrothecomas. Today, the genetic analysis of fresh or fixed solid tumors is enabled by the fluorescent in situ hybridization method (FISH). Using FISH and/or conventional cytogenetics, we analysed 12 ovarian stromal tumors (6 fibromas, 3 fibro thecomas and 3 thecomas). All of these tumors were benign and trisomy 12 was observed in all cases. Moreover, 3 cases presented trisomy and tetrasomy for chromosome 12 simultaneously. The high frequency of trisomy 12 in this tumor type suggests that this abnormality might be implicated in ovarian tumorigenesis.

We report 5 cases of infantile fibrosarcoma (4 boys and 1 girl) whose average age was 5, 7 months (range 0 days to 14 months). The tumor was congenital in 4 cases. All tumors presented in the extremities (forearm, hand, thigh: 1 case, lower leg: 2 cases). Treatment was based on surgery (3 cases: amputation, 2 cases: local excision) with a favorable course in all cases, even those with marginal excision (follow-up ranging from 5 to 21 years). The lesions were characterized by dense monotonous cells growing in a fascicular pattern, with small necrotic areas and scattered lymphocytes. The mitotic index was high (average 8/10 high-power fields). ETV6-NK3 chimeric RNA was detected by reverse transcriptase polymerase chain reaction in two cases out four cases from paraffin-embedded tissue blocks. The infantile fibrosarcoma is a good prognosis tumor characterized by particular histological features and ETV6-NK3 gene fusion.

Differenciated thyroid carcinomas are the most frequently encountered endocrine tumours. These hormono-dependent carcinomas have a good prognosis. Data derived from molecular biology allowed a better understanding of pathophysiological mechanisms involved in tumorigenesis of thyroid papillar and follicular carcinomas. The use of the works derived from molecular biology also allowed a better diagnostic and therapeutic management of the thyroid cancer patients, particularly using recombinant human TSH. Familial thyroid cancer disease must also be recognised to optimise the clinical managemet of patients and their family.

During the past two years, new molecular targets have been discovered which link cell cycle, cell proliferation and cellular growth. It has become more and more evident that whereas gain-of-function mutations in specific genes can lead to cancer, genomic instability plays also an important role in tumour progression. With examples taken from the recent literature, we describe in this short review crucial findings on the molecular mechanisms controlling cell cycle and proliferation. We illustrate how specific combinations of proto-oncogenes alterations can result in tissue-specific tumours. Finally, impairment of the interactions of a cancer cell with its surrounding neighbours is also shown to participate in the progression toward aggressive phenotypes.

The authors report the case of a ten-year-old girl, who had been treated for a malignant germinal tumour five years before, presenting with a leukaemia-like syndrome associating bone pain, liver and spleen nodules and bone marrow involvement. The cyto-pathological analysis showed undifferentiated cells and CD56 and protein S100 were found as the only positive markers. The child received several subsequent lines of chemotherapy and ultimately died of the disease.

Treating cancer by targeting its vasculature is a recent conceptual revolution. The use of newly discovered potent antiangiogenic factors has confirmed the anti-growth and anti-metastatic efficiency of anti-angiogenic therapy in a variety of experimental solid tumour models. Using gene transfer technique to deliver anti-angiogenic molecules in vivo is becoming a widely accepted new approach. This review summarizes the biological basis, current situation and development trends of this new therapy, as well as its promising perspectives in cancer treatment.

The twentieth century has witnessed the discovery of the various genetic alterations that drive a normal cell toward neoplasia. One the challenge of the near future concerns the diagnostic of these alterations and their correlation with clinical parameters such as response to therapy or survival. It will be important to define, for each patient, a specific profile of the various alterations in order to improve and personalize the therapy. It is also essential to understand the various mechanisms of these alterations in order to develop new diagnostic procedures. Furthermore, the relation between genotype and phenotype is not straightforward and can be influence by various parameters such as the localization of the mutation, alterations of other genes or the expression of modifiers genes.

The phenotype of malignant epithelial cells in nasopharyngeal carcinomas (NPC) results from latent infection by the Epstein-Barr virus (EBV) combined to cell gene alterations, especially those affecting the p16/Ink 4 gene. At the site of the primary tumor, NPC are strongly infiltrated by non-malignant EBV-negative T-lymphocytes. There are experimental clues suggesting that these lymphocytes are involved in tumor development, for example by providing anti-apoptotic signals to malignant epithelial cells. The amazing geographic distribution of NPC is accounted for by the conjunction of several risk factors in endemic regions. These risk factors are related to the diffusion of one or several susceptibility genes, the probable existence of viral strains with high oncogenic potential and non-viral environmental factors, especially dietary factors. The perspectives of immunotherapy in NPC are still unclear since viral proteins detected in tumors are poorly immunogenic (EBNA1, LMP1). Targeted molecules designed to interfere with viral and cellular oncoprotein signals will probably have interesting applications for the treatment of NPC.

Cowden disease is an autosomal dominant inherited cancer syndrome characterized by the occurrence of multiple hamartomas, tumors or hyperplastic lesions that may develop in any organ. The disease is related to germline mutation of the PTEN gene, a recently cloned tumor suppressor gene involved in the pathogenesis of sporadic glioblastoma and endometrial carcinoma. It has been shown that the PTEN gene product was a phosphatase able for dephosphorylating a lipid substrate: the phosphatidylinositol (3,4,5)-triphosphate (PIP3). So PTEN appears to negatively control the PI3K-AKT signaling pathway implicated in regulation of cell growth and survival.

The INK4a-ARF locus, localized on 9p21, encodes two tumor suppressor proteins, p16INK4a and p14ARF, acting respectively through the CDK4-pRb and the p53 pathways. Familial melanoma (comprising between 8 and 12% of all melanoma cases) is a genodermatosis transmitted as an autosomal dominant trait, often associated with clinically atypical moles (AN). Germline mutations of p16INK4a are found in up to 20-30% of melanoma prone families. Mutated families often contain more than three family members affected and/or comprise at least one relative with multiple melanomas. Most of these mutations have been shown to affect p16INK4a protein function (i.e. CDK4 binding or pRB phosphorylation). Germline mutations of p16INK4a are also found in a lesser extend in sporadic multiple melanoma and in familial pancreatic cancer. The INK4a-ARF locus plays also an important role in skin carcinogenesis. P16INK4a UV induced mutations (CC:GG > TT:AA tandem transition or C:G > T:A transition at dipyrimidic site) are found in 12% of sporadic skin carcinomas, mainly in epidermoid tumors, and seem to occur independently of p53 mutations. Xeroderma pigmentosum (XP) is characterized by an inheritable DNA repair defect (involving the nucleotid excision repair (NER) system) predisposing to skin carcinomas. In skin tumors from (XP) patients, p16INK4a UV induced mutations occur more frequently, are often multiple, and significantly associated with the presence of p53 mutations. Such data, which could be related to the XP genetic instability and indicates a possible cooperative effect of inactivation of these pathways in the tumoral process of XP skin tumors.