Because of their raised prevalence and mortality, association of secondary tumors and inefficiency of therapeutic conventional (surgery, radio- and chemotherapy), head and neck and lung cancers represent true public health problems. The knowledge of the process of carcinogenesis allowed development of approaches of chemoprevention. The vitamin A and its derivatives showed initially a certain efficacy, but an important toxicity and large trials remained negative. For lung cancers, in the event of continuation of the tobacco, beta-carotene and the vitamin A seem even deleterious. Progress in the biology of cancer should allow innovating new approaches of chemoprevention. Today the most effective strategy stays the stop of the tobacco.

Lung and head and neck cancers result from a multistep process involving activation of oncogenes and inactivation of tumor-suppressor genes. These two processes share common features and molecular players, while their corresponding clinical entities are both triggered by the tobacco carcinogens. In many cases, the molecular abnormalities associated with these multi-step and multi-focal processes can be found in pre-malignant lesions and normal tissue. The growing knowledge of the molecular basis of lung and head and neck carcinogenesis allows to better selecting molecular alterations that can be modulated by molecular targeted agents either in a curative or in a chemopreventive approach.

The family of NF-kappaB transcription factors plays a key role in diverse biological processes, such as inflammatory and immune responses, cell survival and tumor development. A new NF-kappaB activation pathway has been recently uncovered, the so-called alternative NF-kappaB activation pathway. It has been shown that this pathway mainly controls the activity of RelB, a member of the NF-kappaB family, and its activation requires IKKalpha, one of the two catalytic subunits of the IKK complex. Recent studies suggest that constitutive activation of the alternative pathway may be involved in tumor development, but most surprisingly it is also reported that IKKalpha exerts a protective function against uncontrolled cell proliferation and cancer development. This review discusses recent progresses in the understanding on how the alternative pathway may participate in cancer development, focusing more specifically on RelB and IKKalpha.

microRNAs constitute one of the most important discovery in the past few years in the field of gene expression regulation. They can precisely regulate the expression of a specific protein by inhibiting its translation and/or promoting the degradation of its mRNA. In several cancers, the expression of some microRNAs is misregulated, pointing toward the existence of microRNAs with oncogenic or tumour suppressor properties. The miR-17-92 miRNA cluster has been reported to have a pro-oncogenic role in a mouse model system of Myc-induced B cell lymphoma. Some of its targets mRNAs code for proteins with pro-apoptotic or anti-proliferative functions, which shed some light on the mechanism of action of this cluster. On the other hand, a tumour suppressor miRNA like let-7 targets mRNAs coding for oncogenes and is frequently down-regulated in cancers. The finding that c-Myc controls the expression of several of these microRNAs reveals new information on how misregulation of this proto-oncogene can promote tumorigenesis.

The occurrence of metastasis is probably the least characterised process in tumour progression. It is difficult to study, due to the limited access to metastatic tissues, to the multiple steps involved and the long time required to observe metastasis growth, even in model systems. Our understanding of metastatic processes has been changed in recent years by a number of observations and the development of new concepts.

Juxtaglomerular-cell tumor (JGCT), first described in 1967, is a rare tumor of the kidney that derives from specialized smooth-muscle cells of the wall of the glomerular afferent arteriole. Less than 100 cases have been published, mainly as single-case reports or small series. JGCTs are considered benign, but the clinical follow-up has been short in most reported cases. Only one metastatic case has been reported to date, raising the question of tumors of uncertain malignant potential rather than clearly benign neoplasms. Genomic features have been studied in only two cases that showed gains on chromosome 10 as well as deletions on chromosomes 9, 11q and X. The present work studied the genomic characteristics of two additional cases of JGCT by CGH. Similarly to the two previously reported cases, these two tumors showed losses on chromosomes 9 and 11, suggesting recurrent chromosomal imbalances. In addition, one case showed gains and losses of entire chromosomes similar to a previous case studied by karyotyping. Such an aneuploid karyotype may reflect a potential for malignancy as previously reported. Thus, JGCT might be better considered as a tumor of uncertain malignant potential consequently requiring a prolonged follow-up. Future clinicopathologic and genomic studies of large retrospective and prospective series may help to better understand the biology of this fascinating entity.

Prostate cancer with 60,000 new cases a year is a public health problem which requires adapted and effective responses. The era of PSA screening dramatically increased the number of prostate biopsies that pathologists have to screen and consequently the number of difficult cases requiring analysis. Immunohistochemistry with anti-AMACR/p504s is useful for detecting prostate cancer in the full range of prostate specimens encountered in needle biopsies. In particular, studies to date with AMACR/p504s clearly demonstrate the ability of this marker to support a diagnosis of malignancy in prostate needle biopsies, combined with negative staining for a basal cell marker, such as p63. This study conducted by the Prostate Committee of the French Association of quality assurance in pathological anatomy and cytology (AFAQAP), reports the evaluation of the current practices with available anti-p63 and -p504s antibodies. The results of this investigation show a correct evaluation of the immunostaining procedure. Overall, from the 39/56 structures tested, the value of the test was positive in 85%. The best results were obtained after antigenic restoration with TRIS-EDTA pH 9, p504s (13H4, 1/200) and p63 (A4A, 1/100).

Most adrenocortical tumors are benign; adrenocortical carcinomas are rare but their prognosis is poor and few therapeutic options are available. In most adrenocortical tumors, the morphological approach provides enough elements to establish the differential diagnosis between a benign and a malignant tumor but in few cases, it is insufficient. Moreover, morphology is limited for predicting prognosis of adrenocortical carcinomas. These observations led to development of other approaches, in particular immunohistochemical and genetic approaches. The comprehension of the genetic syndromes associated with adrenocortical tumors led to progress in the identification of genetic abnormalities involved in sporadic adrenocortical tumorigenesis. Thus, in sporadic adrenocortical tumorigenesis, IGF-II overexpression and cyclin E overproduction have been associated with 11p15 alterations which are observed in Bethwith-Wiedemann syndrome and TP53 inactivating mutations and 17p13 locus abnormalities which are observed in Li-Fraumeni syndrome. Activation of the Wnt/ss-catenin signaling pathway which is observed in familial adenomatous polyposis has been found in adrenocortical adenomas and carcinomas associated to mutations of CTNNB1, the gene coding ss-catenin, suggesting a central role for this pathway in adrenocortical tumorigenesis. These genetics findings already have had repercussions for patients via the development of molecular markers for diagnosis and prognosis; in the future they should be helpful in the development of new therapeutics.

Classification of adult renal-cell tumors, based for years on histological criteria only, has been recently updated by taking into account characteristic chromosome rearrangements and genome and transcriptome profiles identified by cytogenetic techniques, detection of fusion transcripts and by genomic analyses on DNA microarrays. Papillary carcinomas are divided into two types. Type 1 is characterized by trisomies 7 and 17, and 12, 16, and 20. Type 2 is a heterogeneous group, including a low-grade subtype corresponding to genetically evolved type 1 tumors, and a high-grade subtype, identified by its expression profile which remains to be well characterized at the genomic level. Mucinous tubular carcinoma exhibits a recurrent genomic profile with whole chromosome losses involving 1, 4, 6, 8, 9, 13, 14, 15, and 22, consequently without relationship with type 1 papillary tumors. The profile of chromophobe-cell carcinoma corresponds to the same genomic mechanism, with losses of chromosomes 1, 2, 6, 10, 13, 17, and 21, without relationship with that of oncocytoma. Juvenile carcinoma, that can occur also in adults, shows translocations involving genes of the MiTF/TFE family, TFE3, in Xp11.2, and TFEB, in 6p21. So, molecular diagnosis, either by identification of specific translocations, or by genomic profiling, can be of valuable help for typing renal tumors when histological classification is difficult.