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B Franc

Publications and source records attributed to B Franc.

At least 19 recordsLinked to original sources
PubMed2006

Prognosis of stage II colon cancer by non-neoplastic mucosa gene expression profiling.

We have assessed the possibility to build a prognosis predictor (PP), based on non-neoplastic mucosa microarray gene expression measures, for stage II colon cancer patients. Non-neoplastic colonic mucosa mRNA samples from 24 patients (10 with a metachronous metastasis, 14 with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. Patients were repeatedly and randomly divided into 1000 training sets (TSs) of size 16 and validation sets (VS) of size 8. For each TS/VS split, a 70-gene PP, identified on the TS by selecting the 70 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Mean prognosis prediction performances of the 70-gene PP were 81.8% for accuracy, 73.0% for sensitivity and 87.1% for specificity. Informative genes suggested branching signal-transduction pathways with possible extensive networks between individual pathways. They also included genes coding for proteins involved in immune surveillance. In conclusion, our study suggests that one can build an accurate PP for stage II colon cancer patients, based on non-neoplastic mucosa microarray gene expression measures.

Adenocarcinoma↗
PubMed2005

Absence of a specific radiation signature in post-Chernobyl thyroid cancers.

Thyroid cancers have been the main medical consequence of the Chernobyl accident. On the basis of their pathological features and of the fact that a large proportion of them demonstrate RET-PTC translocations, these cancers are considered as similar to classical sporadic papillary carcinomas, although molecular alterations differ between both tumours. We analysed gene expression in post-Chernobyl cancers, sporadic papillary carcinomas and compared to autonomous adenomas used as controls. Unsupervised clustering of these data did not distinguish between the cancers, but separates both cancers from adenomas. No gene signature separating sporadic from post-Chernobyl PTC (chPTC) could be found using supervised and unsupervised classification methods although such a signature is demonstrated for cancers and adenomas. Furthermore, we demonstrate that pooled RNA from sporadic and chPTC are as strongly correlated as two independent sporadic PTC pools, one from Europe, one from the US involving patients not exposed to Chernobyl radiations. This result relies on cDNA and Affymetrix microarrays. Thus, platform-specific artifacts are controlled for. Our findings suggest the absence of a radiation fingerprint in the chPTC and support the concept that post-Chernobyl cancer data, for which the cancer-causing event and its date are known, are a unique source of information to study naturally occurring papillary carcinomas.

Adenoma↗
PubMed2004

Loss of heterozygosity on 10q and mutational status of PTEN and BMPR1A in colorectal primary tumours and metastases.

We investigated the possible role of chromosome 10q losses in colorectal cancer metastasis by carrying out an allelic imbalance study on a series of microsatellite instability-negative (MSI-) primary tumours (n=32) and metastases (n=36) from 49 patients. Our results demonstrate that 10q allelic losses are associated with a significant proportion (25%) of MSI- colorectal tumours, but are not involved in the metastatic process. PTEN and BMPR1A, two genes located in the common deleted region, were screened for mutations in samples with loss of heterozygosity. The absence or low frequency of mutations indicates that the inactivation of these genes by deletion of one allele and mutation of the other one plays only a minor role in MSI- tumours.

Base Sequence↗
PubMed2004

[The cost of Mohs micrographic surgery for basal cell carcinoma. The Ambroise Paré hospital's experience (Boulogne, France)].

OBJECTIVE: Mohs'micrographic surgery is generally considered as the best procedure for the treatment of difficult basal cell carcinomas. It is supposed to be costly, but an economic evaluation, with a cost-outcome analysis, is necessary to estimate the actual contribution of this procedure in skin cancer treatment, in comparison with the reference procedure, i.e. traditional surgical excision. Our aim was to evaluate the actual cost of Mohs'surgery applied on basal cell carcinoma treatment in France. METHODS: The charts of 97 patients treated by Mohs'surgery between january 1997 and july 2001 in a teaching hospital near Paris (Ambroise Paré hospital, Boulogne), where Mohs'surgery is exclusively performed in France, were reviewed. Direct costs were derived from resource utilization of staff and material required for Mohs'surgery, estimated by a micro-costing method. Indirect costs and total costs were then calculated. RESULTS: When adding surgery and pathology facility costs, mean direct and total costs per basal cell carcinoma were 776.0 (range: 538.4-1273.9), and 1014.6 Euros (range: 777-1512.4), respectively. When including costs of diagnosis, the average total cost per procedure was 1084.3 Euros. DISCUSSION: These costs appear higher than those obtained with other methods of valuation of hospital costs used in France, but they are slightly lower than those found in the literature. The next stage will be to estimate, in the same way, the cost of traditional surgical excision for the same type of lesions, and to calculate the incremental cost-effectiveness ratio between the two procedures, with rate of recurrence at five years as the effectiveness outcome.

Adult↗
PubMed2004

[Treatment of dermatofibroma protuberans with fixed Mohs' micrographic surgery].

INTRODUCTION: Dermatofibrosarcoma protuberans is a tumor of intermediate malignancy characterized by its aggressive local growth due to pseudopodium-like outgrowths and marked propensity to recur after surgical excision. To achieve complete cure with conventional surgery, surgical margins up to 5 cm are required, leading to wide scars. Mohs' micrographic surgery is used for the removal of certain malignant tumors, both ensuring complete excision by examination of all margins as well as minimizing normal tissue loss. However, differentiating minimal residual tumor from normal skin can be difficult on the frozen sections used in Mohs' micrographic surgery. Our aim was to develop a procedure of Mohs' micrographic surgery in conjunction with rush formalin-fixed, paraffin-embedded tangential sections. PATIENTS AND METHODS: Ten consecutive cases have been prospectively treated since 1998. Under local anesthesia, the tumor was first excised including lateral margin of 1 cm and a deep margin including the underlying muscle aponevrosis. A 2 to 3 mm thick horizontal section of the surgical bed was then removed, rush formalin-fixed, paraffin-embedded, tangentially sectioned, hematin-eosin stained, and eventually stained with an anti-CD34 monoclonal antibody. While waiting for pathology results, the surgical bed was not definitively closed. If excision was incomplete, an oriented complementary excision was performed. RESULTS: Excision was complete after the first stage in 7 patients and incomplete only deeply in 3. Lateral surgical margins were reduced to 1.3 cm in all patients, facilitating wound closure: direct suture (5 patients), controlled wound healing (3 patients) or flap coverage (2 patients). No recurrence has been observed after a mean follow-up of 26 months. DISCUSSION: The use of Mohs' micrographic surgery in conjunction with rush formalin-fixed, paraffin-embedded tangential sections reduce surgical margins in dermatofibrosarcoma protuberans. This procedure would be interesting in difficult sites, such as the genitalia, the breast, or the periarticular regions. Other cases, and longer follow-up are however necessary to validate this promising technique.

Adult↗
PubMed2004

[Mohs' micrographic surgery: history, principles, critical analysis of its efficacy and indications].

OBJECTIVES: To systematically review the literature for studies reporting on the role of Mohs' micrographic (MMS) surgery in the treatment of skin tumors. To show how it is performed in France. DESIGN: We reviewed with a quality grid all studies indexed in MEDLINE before 2003/01/01 and published in English or French. Data were extracted by two independent reviewers. MAIN OUTCOME MEASURES: Quality of clinical studies, recurrence rates, number of patients lost to follow-up. RESULTS: No randomized study was found among the 493 references found. Studies of lower quality, on procedures similar to MMS, or previous systematic reviews were therefore selected. In tumors such as basal (BCC) or spinous (SCC) cell carcinoma, microcystic adnexal carcinoma, dermatofibrosarcoma protuberans, and Merkel cell carcinoma, MMS commonly induced lower recurrence rates than figures reported for conventional treatments and/or reduced surgical margins. Studies on melanoma were of low quality. CONCLUSIONS: Although no evidence-based guidelines could be developed, MMS should be used mainly for larger, morphea, micronodular or infiltrative-type, or recurrent BCCs located in danger zones, but also (sometimes with a slightly modified procedure) in microcystic adnexal carcinomas, dermatofibrosarcoma protuberans, Merkel cell carcinoma, and in aggressive forms of SCC. Randomized, controlled studies should be performed.

Humans↗
PubMed2003

Histological validation of diagnoses of thyroid cancer among adults in the registries of Belarus and the Ukraine.

In order to evaluate the diagnostic reliability of the thyroid cancers listed in adult registries from the Ukraine and Belarus, a histological review was organised of 327 randomly selected thyroid carcinoma cases diagnosed between 1980 and 1999. A final diagnosis was reached at a 5-day consensus conference by six pathologists who met around a multiheaded microscope. The study concluded with a comparison between the final diagnosis and the initial diagnosis. The pathologists agreed with the initial diagnosis of malignancy in 286 cases (88%). A final diagnosis of papillary, follicular or medullary thyroid carcinoma was reached in 86, 4, and 6% of the cases respectively. In 2.8% of the cases reviewed, diagnostic discrepancies persisted. The percentage of agreement between the final diagnosis and the initial diagnosis was 93%, with a weighted kappa-statistic of 0.61 (confidence interval 95% (CI(95%)): [0.45-0.77]). In all, 89% of the 286 confirmed cancer cases were in agreement for the type of cancer, with a kappa-statistic of 0.56 (CI(95%): [0.43-0.69]). The level of agreement differed according to cancer categories, with concordance rates of 94, 40 and 33% for papillary, follicular and medullary thyroid carcinomas respectively. The low prevalence of follicular thyroid carcinomas in the adult population studied calls for further exploration. The discrepancies and classification difficulties encountered were analysed.

Adolescent↗
PubMed2003

Correlation between the loss of thyroglobulin iodination and the expression of thyroid-specific proteins involved in iodine metabolism in thyroid carcinomas.

Progress in biotechnology has provided useful tools for tracing proteins involved in thyroid hormone synthesis in vivo. Mono- or polyclonal antibodies are now available to detect on histological sections the Na(+)/I(-) symporter (NIS) at the basolateral pole of the cell, the putative iodide channel (pendrin) at the apical plasma membrane, thyroperoxidase (TPO), and members of the NADPH-oxidase family, thyroid oxidase 1 and 2 (ThOXs), part of the H(2)O(2)-generating system. The aim of this study was to correlate thyroglobulin (Tg) iodination with the presence of these proteins. Tg, T(4)-containing Tg, NIS, pendrin, TPO, ThOXs, and TSH receptor (TSHr) were detected by immunohistochemistry on tissue sections of normal thyroids and various benign and malignant thyroid disorders. Tg was present in all cases. T(4)-containing Tg was found in the adenomas, except in Hurthle cell adenomas. It was never detected in carcinomas. NIS was reduced in all types of carcinomas, whereas it was detected in noncancerous tissues. Pendrin was not expressed in carcinomas, except in follicular carcinomas, where weak staining persisted. TPO expression was present in insular, follicular carcinomas and in follicular variants of papillary carcinomas, but in a reduced percentage of cells. It was below the level of detection in papillary carcinomas. The H(2)O(2)-generating system, ThOXs, was found in all carcinomas and was even increased in papillary carcinomas. Its staining was apical in normal thyroids, whereas it was cytoplasmic in carcinomas. The TSHr was expressed in all cases, but the intensity of the staining was decreased in insular carcinomas. In conclusion, our work shows that all types of carcinomas lose the capacity to synthesize T(4)-rich, iodinated Tg. In follicular carcinomas, this might be due to a defect in iodide transport at the basolateral pole of the cell. In papillary carcinomas, this defect seems to be coupled to an altered apical transport of iodide and probably TPO activity. The TSHr persists in virtually all cases.

Biomarkers↗
PubMed2001

No evidence of somatic FGFR3 mutation in various types of carcinoma.

Germline specific point mutations in the gene encoding fibroblast growth factor receptor 3 (FGFR3) are associated with autosomal dominant human skeletal dysplasia and craniosynostosis syndromes. Mutations identical to the germinal activating mutations found in severe skeletal dysplasias have been identified in certain types of cancer: at low frequency in multiple myeloma and cervix carcinoma and at high frequency in bladder carcinoma. We analysed, by SSCP and sequencing, the prevalence of FGFR3 mutations in 116 primary tumours of various types (upper aerodigestive tract, oesophagus, stomach, lung and skin). The regions analysed encompassed all FGFR3 point mutations previously described in severe skeletal dysplasia and cancers. No mutations were detected in the tumour types examined, suggesting that FGFR3 mutations are restricted to a few tumour types, the evidence to date suggesting that they are very specific to bladder carcinomas.

Bone Diseases, Developmental↗
PubMed2001

Analyses of MYC, ERBB2, and CCND1 genes in benign and malignant thyroid follicular cell tumors by real-time polymerase chain reaction.

The roles of the MYC, ERBB2, and CCND1 genes in thyroid carcinogenesis are poorly known. We used real-time quantitative polymerase chain reaction (PCR) assays based on fluorescent TaqMan methodology to quantify MYC, ERBB2, and CCND1 gene amplification and expression in 24 benign tumors (adenomas and goiter nodules) and 12 carcinomas (9 papillary, 2 follicular, and 1 anaplastic) of the thyroid. Real-time PCR is a recently developed method for nucleic acid quantification in homogeneous solutions, and has the potential to become a reference in terms of performance, accuracy, sensitivity, wide dynamic range, excellent interlaboratory agreement, and high throughput capacity, while avoiding the need for tedious post-PCR processing. Overexpression (>5 standard deviations above mean for normal thyroid tissues) of the ERBB2 and CCND1 genes was observed (3.2- to 5.2-fold and 3.8- to 8.4-fold, respectively) in 5 (14%) and 13 (36%) of 36 neoplastic thyroid RNA samples, respectively. Overexpression of the CCND1 gene was observed in both the benign and malignant thyroid tumors, whereas the ERBB2 gene was mainly overexpressed in malignant thyroid tumors. None of the neoplastic thyroid samples overexpressed MYC. No MYC, ERBB2, or CCND1 gene amplification was identified. These results suggest that the CCND1 gene plays an early role and the ERBB2 gene a later role in thyroid tumorigenesis.

Adenoma↗
PubMed2001

Defective mitochondrial ATP synthesis in oxyphilic thyroid tumors.

Oxyphilic tumors (oncocytomas or Hürthle cell tumors) form a rare subgroup of thyroid tumors characterized by cells containing abundant mitochondria. The relationship between the mitochondrial proliferation and the pathogenesis of these tumors is unknown. We have assessed the expression of the mitochondrial ND2 and ND5 (subunits of the nicotinamide adenine dinucleotide dehydrogenase complex) genes and the nuclear UCP2 (uncoupling protein 2) gene in 22 oxyphilic thyroid tumors and matched controls. The consumption of oxygen in mitochondria from tumors was determined by polarography. ATP assays were used to explore the mitochondrial respiratory chain activity and the oxidative phosphorylation coupling in seven fresh thyroid tumors and controls. Adenosine triphosphate synthesis was significantly lower in all the tumors, compared with controls, suggesting that a coupling defect in oxidative phosphorylation may be a cause of mitochondrial hyperplasia in oxyphilic thyroid tumors.

Adenoma, Oxyphilic↗
PubMed2001

Clinical impact of (18)F-FDG PET in thyroid carcinoma patients with elevated thyroglobulin levels and negative (131)I scanning results after therapy.

UNLABELLED: 18F-FDG PET has been shown to effectively detect differentiated thyroid carcinoma (DTC) metastases with impaired iodine-trapping ability. This article evaluates the potential contribution of FDG PET in the follow-up of patients with differentiated thyroid carcinoma, elevated thyroglobulin (Tg) levels, and negative whole-body scan results obtained after high doses of (131)I. METHODS: We prospectively assessed the ability of FDG to detect metastases in 37 DTC patients who had undergone total thyroidectomy and radioactive ablation and presented with persistent disease, as assessed from elevated Tg levels and negative results of whole-body scans performed after therapeutic doses of (131)I. Additional conventional imaging procedures were performed to detect residual disease, and the patients were divided into 2 groups: group 1, with positive conventional imaging findings (n = 10), and group 2, with negative conventional imaging findings (n = 27). RESULTS: FDG PET showed positive findings in 28 patients and accurately localized tumor sites in 89% of them. In group 1, FDG PET confirmed 17 of 18 previously known tumor sites and detected 11 additional sites. In group 2, FDG PET findings were positive in 19 of 27 patients with no previously detected metastases. PET was effective for both low- and high-stage tumors. The FDG data led to a change in the clinical management of 29 of 37 patients with further surgical resection in 23 patients, 14 of whom achieved disease-free status, and external radiation therapy in 4 patients. CONCLUSION: FDG PET is able to detect metastases undetected by (131)I posttherapy whole-body scanning in patients with elevated Tg levels. It should be proposed as a first-line investigation in patients with persistent disease but negative findings on (131)I whole-body scans after treatment.

Adult↗
PubMed2000

Prognostic and immunohistochemical validation of the capella classification of pancreatic neuroendocrine tumours: an analysis of 82 sporadic cases.

AIMS: To study the clinical outcome of 82 cases of pancreatic neuroendocrine tumours classified according to the recent histological and prognostic classification of Capella. METHODS AND RESULTS: Eighty-two surgical cases of pancreatic neuroendocrine tumours were examined histologically with immunohistochemical staining of paraffin sections using streptavidin-biotin complex and application of antibodies against chromogranin A and 10 hormonal peptides. Classification in four groups correlated with long follow-up and outcome of these cases. Histological examination showed 30 group I, four group II, 41 group III and seven group IV tumours. Twenty-one (70%) of group I tumours were insulinomas, whereas 25% of group III tumours were glucagonomas and 25% were unclassified. Most group IV tumours were unclassified, showing no immunohistochemical staining with any of the 10 hormonal peptides tested. Outcome was clearly correlated with tumour group. Among the 14 patients who died of the disease, four had group IV and 10 group III tumours. Thus, unclassified asymptomatic tumours without immunohistochemical staining had a poorer prognosis than asymptomatic tumours with staining. CONCLUSION: This study validates the Capella classification as easy to apply and useful in predicting clinical outcome.

Adult↗
PubMed2000

Diagnosis and treatment of medullary thyroid cancer.

Medullary carcinoma of the thyroid (MTC) is a rare tumour derived from thyroid C cells with serum calcitonin as a specific and sensitive marker. MTC is inherited in 25% of cases, with an autosomal dominant transmission, age-related penetrance and variable expressivity. MTC is an obligatory component of multiple endocrine neoplasia type 2 (MEN2), which comprises three well defined syndromes: MEN2A, which may be associated with pheochromocytoma and/or hyperparathyroidism; the much rarer MEN2B, which occurs early and is accompanied by developmental abnormalities; while in contrast, familial MTC (FMTC) is not associated with any endocrinopathy. The RET proto-oncogene is the causative gene of the MEN2 syndromes and mutations in this gene are found in >90% of inherited cases, allowing easier and more reliable family screening than pentagastrin stimulation tests. Nevertheless, the correlation between the genotype and the different clinical phenotypes is not perfect. The prognosis of MTC depends on its staging at presentation, and the early appearance of cervical lymph node metastases emphasizes the need for extensive surgery, although many patients still do not normalize calcitonin levels post-operatively, and they remain a challenge for the further management.

Calcitonin↗
PubMed2000

Characterization of autonomous thyroid adenoma: metabolism, gene expression, and pathology.

Fifty-one in vivo characterized autonomous single adenomas have been studied for functional parameters in vitro, for gene and protein expression and for pathology, and have been systematically compared to the corresponding extratumoral quiescent tissue. The adenomas were characterized by a high level of iodide trapping that corresponds to a high level of Na+ /iodide symporter gene expression, a high thyroperoxidase mRNA and protein content, and a low H2O2 generation. This explains the iodide metabolism characteristics demonstrated before, ie, the main cause of the "hot" character of the adenomas is their increased iodide transport. The adenomas spontaneously secreted higher amounts of thyroid hormone than the quiescent tissue and in agreement with previous in vivo data, this secretion could be further enhanced by thyrotropin (TSH). Inositol uptake was also increased but there was no spontaneous increase of the generation of inositol phosphates and this metabolism could be further activated by TSH. These positive responses to TSH are in agreement with the properties of TSH-stimulated thyroid cells in vitro and in vivo. They are compatible with the characteristics of mutated TSH receptors whose constitutive activation accounts for the majority of autonomous thyroid adenomas in Europe. The number of cycling cells, as evaluated by MIB-1 immunolabeling was low but increased in comparison with the corresponding quiescent tissue or normal tissue. The cycling cells are observed mainly at the periphery; there was very little apoptosis. Both findings account for the slow growth of these established adenomas. On the other hand, by thyroperoxidase immunohistochemistry, the whole lesion appeared hyperfunctional, which demonstrates a dissociation of mitogenic and functional stimulations. Thyroglobulin, TSH receptor, and E-cadherin mRNA accumulations were not modified in a consistent way, which confirms the near-constitutive expression of the corresponding genes in normal differentiated tissue. On the contrary, early immediate genes expressions (c-myc, NGF1B, egr 1, genes of the fos and jun families) were decreased. This may be explained by the proliferative heterogeneity of the lesion and the previously described short, biphasic expression of these genes when induced by mitogenic agents. All the characteristics of the autonomous adenomas can therefore be explained by the effect of the known activating mutations of genes coding for proteins of the TSH cyclic adenosine monophosphate (cAMP) cascade, all cells being functionally activated while only those at the periphery multiply. The reason of this heterogeneity is unknown.

Adenoma↗
PubMed1999

Key role of 5-HT1B receptors in the regulation of paradoxical sleep as evidenced in 5-HT1B knock-out mice.

The involvement of 5-HT1B receptors in the regulation of vigilance states was assessed by investigating the spontaneous sleep-waking cycles and the effects of 5-HT receptor ligands on sleep in knock-out (5-HT1B-/-) mice that do not express this receptor type. Both 5-HT1B-/- and wild-type 129/Sv mice exhibited a clear-cut diurnal sleep-wakefulness rhythm, but knock-out animals were characterized by higher amounts of paradoxical sleep and lower amounts of slow-wave sleep during the light phase and by a lack of paradoxical sleep rebound after deprivation. In wild-type mice, the 5-HT1B agonists CP 94253 (1-10 mg/kg, i.p.) and RU 24969 (0.25-2.0 mg/kg, i.p.) induced a dose-dependent reduction of paradoxical sleep during the 2-6 hr after injection, whereas the 5-HT1B/1D antagonist GR 127935 (0.1-1.0 mg/kg, i.p.) enhanced paradoxical sleep. In addition, pretreatment with GR 127935, but not with the 5-HT1A antagonist WAY 100635, prevented the effects of both 5-HT1B agonists. In contrast, none of the 5-HT1B receptor ligands, at the same doses as those used in wild-type mice, had any effect on sleep in 5-HT1B-/- mutants. Finally, the 5-HT1A agonist 8-OH-DPAT (0.2-1.2 mg/kg, s.c.) induced in both strains a reduction in the amount of paradoxical sleep. Altogether, these data indicate that 5-HT1B receptors participate in the regulation of paradoxical sleep in the mouse.

Analysis of Variance↗