Gene expression profiling identifies molecular subgroups among nodal peripheral T-cell lymphomas.

The classification of peripheral T-cell lymphomas (PTCL) is still a matter of debate. To establish a molecular classification of PTCL, we analysed 59 primary nodal T-cell lymphomas using cDNA microarrays, including 56 PTCL and three T-lymphoblastic lymphoma (T-LBL). The expression profiles could discriminate angioimmunoblastic lymphoma, anaplastic large-cell lymphoma and T-LBL. In contrast, cases belonging to the broad category of 'PTCL, unspecified' (PTCL-U) did not share a single molecular profile. Using a multiclass predictor, we could separate PTCL-U into three molecular subgroups called U1, U2 and U3. The U1 gene expression signature included genes known to be associated with poor outcome in other tumors, such as CCND2. The U2 subgroup was associated with overexpression of genes involved in T-cell activation and apoptosis, including NFKB1 and BCL-2. The U3 subgroup was mainly defined by overexpression of genes involved in the IFN/JAK/STAT pathway. It comprised a majority of histiocyte-rich PTCL samples. Gene Ontology annotations revealed different functional profile for each subgroup. These results suggest the existence of distinct subtypes of PTCL-U with specific molecular profiles, and thus provide a basis to improve their classification and to develop new therapeutic targets.

Prediction of metastasis risk (11 year follow-up) using VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 expression in breast cancer (n=905).

Neoangiogenesis in tumours contributes to the development of blood-borne metastases, and can be evaluated by markers of activated endothelial cells in preference to panendothelial markers. Our purpose was to document the prognostic significance of VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 immunoexpression in breast carcinoma frozen samples (n=905, follow-up=11.7 years). We observed that: (i). CD105 (P=0.001) and Tie-2/Tek (P=0.025) (but not VEGF-R1 and VEGF-R2) overexpression correlated with a shorter survival, and were (Cox's model) independent histoprognostic indicators; (ii). only CD105 marked expression correlated (P=0.035) with a shorter survival of node-negative patients; (iii). three markers - CD105 (P=0.001), Tie-2/Tek (P=0.01), VEGF-R1 (P=0.001), but not VEGF-R2 - correlated with metastatic risk in node-negative patients in univariate analysis; and (iv). VEGF-R1 (P=0.01) expression correlated with high local recurrence risk. It is concluded that CD105 and to a lesser extent Tie-2/Tek and VEGF-R1, but not VEGF-R2 are endowed with prognostic significance that may be useful for patient monitoring, particularly CD105 expression for selecting node-negative patients for more aggressive postsurgery therapy.

[Late effects of radiations on the liver]. / Effets tardifs des radiations sur le foie.

Until recently, the liver was classified as a radioresistant organ, although it is in fact highly radiosensitive. The realization that the whole liver could be treated safely only with low doses of radiation led to the conclusion that radiation therapy had an extremely limited role in the treatment of intrahepatic malignancies. A resurgence of interest has been observed with the advent of conformal radiotherapy and the introduction of bone marrow transplantation with total body irradiation. The radiation-induced liver disease, often called radiation hepatitis, is a syndrome characterized by the development of anicteric ascites, approximately 2 weeks to 4 months after hepatic irradiation. Immediate tolerance is generally surprisingly good, and the subacute radiation injury is followed by a complete asymptomatic healing, although the late lesions may be associated with signs of chronic radiation hepatitis. Radiation hepatitis must be distinguished from chemoradiation-induced-hepatitis occurring in patients undergoing bone marrow transplantation and total body irradiation. Both syndromes demonstrate the same pathological lesion: veno-occlusive disease. The main treatment for radiation hepatitis is diuretics, although soma advocate steroids for severe cases.

[Late effects of radiations on mature and growing bone]. / Effets tardifs des radiations sur l'os mature et en croissance.

The physiopathology of radiation-induced bone damage is no completely elucidated. Ionizing radiation may induce an inhibition or an impairment of growing bone. This fact is of particular importance in children, and represents one of the most important dose-limiting factors in the radiotherapeutic management of children with malignant diseases. Scoliosis, epiphyseal slippage, avascular necrosis, abnormalities of craniofacial growth may be observed after radiation. Child's age at the time of treatment, location of irradiated bone and irradiation characteristics may influence the radiation-related observed effects. In adults, pathological analysis of mature bone after ionizing radiation exposure are rare, suggesting that it is difficult to draw a clear feature of the action of radiation on the bone. Osteoporosis, medullary fibrosis and cytotoxicity on bone cells lead to fracture or necrosis. Various factors can influence bone tolerance to radiation such as bone involvement by tumor cells or infection, which is frequent is mandibulary osteoradionecrosis. Technical improvements in radiation techniques have also decreased radio-induced bone complications: the volume, fractionation and total dose are essential to consider. The absence of a consistent radiation-induced late effects evaluation scale has hampered efforts to analyze the influence of various therapeutic maneuvers and the comparison of results from different reported series. The currently proposed evaluation scale may help harmonizing the classification of radiation-induced bone late effects.