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Frédéric Bibeau

Publications and source records attributed to Frédéric Bibeau.

16 recordsLinked to original sources
PubMed2006

Liver metastases in prostate carcinoma: clinical characteristics and outcome.

OBJECTIVE: To assess the clinical characteristics and outcome of patients with liver metastases in prostate carcinoma. PATIENTS AND METHODS: From January 1995 to December 2005, 345 patients with metastatic prostate cancer were prospectively recorded in the database of the Montpellier Cancer Centre, France. The clinical characteristics and outcome of 28 patients who developed liver metastases during the course of the disease were analysed. RESULTS: Six patients had liver metastases as the first site of metastatic disease, and for one of them, liver was the only metastatic site. All but one patient had hormone-refractory disease. Serum measurement of neuroendocrine markers showed increased levels of chromogranin A and neurone-specific enolase in 84% and 44% of patients, respectively. Six patients had a pathological analysis; there were two different histological patterns in liver biopsies, i.e. four were adenocarcinomas with a moderate (one patient) or poor (three) differentiation and two were neuroendocrine carcinomas. Three patients had no treatment because of a poor performance status. One patient had hormone therapy for synchronous liver metastases at diagnosis as the first-line treatment; other patients were treated with chemotherapy. The median (range) overall survival was 6 (1-27) months; the median survival of patients for whom liver was part of the initial metastatic pattern was 14 months. CONCLUSION: Liver metastases are not very rare but appear to be a rather late event in the course of the disease. They are frequently associated with neuroendocrine characteristics.

Adenocarcinoma↗
PubMed2006

High inter-observer agreement in immunohistochemical evaluation of HER-2/neu expression in breast cancer: a multicentre GEFPICS study.

The accurate determination of HER-2 in invasive breast cancer has become a critical issue, particularly in the context of the results of recent trastuzumab (Herceptin((R))) adjuvant trials. This multicentre study evaluated inter-observer reproducibility in interpretation of HER-2 immunostains performed in different laboratories according to their in-house technique. A total of 74 HER-2 immunostains were evaluated by 16 pathologists and by a central review committee. As determined by central review, the HER-2 score was 0 in 33 cases (44%), 1+ in 10 cases (13%), 2+ in 9 cases (12%) and 3+ in 23 cases (31%). The overall kappa value was good (kappa=0.75). Agreement was excellent for the 0/1+ group (kappa=0.85) and for the 3+ group (kappa=0.82). As expected, the score 2+ group showed poor agreement (kappa=0.38). A quality assurance process showed that ring studies and adherence to national guidelines greatly improve inter-observer reproducibility.

Adult↗
PubMed2006

Snail and slug play distinct roles during breast carcinoma progression.

PURPOSE: Carcinoma progression is linked to a partially dedifferentiated epithelial cell phenotype. As previously suggested, this regulation could involve transcription factors, Snail and Slug, known to promote epithelial-mesenchymal transitions during development. Here, we investigate the role of Snail and Slug in human breast cancer progression. EXPERIMENTAL DESIGN: We analyzed Snail, Slug, and E-cadherin RNA expression levels and protein localization in large numbers of transformed cell lines and breast carcinomas, examined the correlation with tumor histologic features, and described, at the cellular level, Snail and Slug localization in carcinomas using combined in situ hybridization and immunolocalization. RESULTS: In contrast with transformed cell lines, Slug was found to colocalize with E-cadherin at the cellular level in normal mammary epithelial cells and all tested carcinomas. Snail also colocalized at the cellular level with E-cadherin in tumors expressing high levels of Snail RNA. In addition, Snail was significantly expressed in tumor stroma, varying with tumors. Slug and Snail genes were significantly overexpressed in tumors associated with lymph node metastasis. Finally, the presence of semidifferentiated tubules within ductal carcinomas was linked to Slug expression levels similar to or above normal breast samples. CONCLUSIONS: These results suggest that Snail or Slug expression in carcinoma cells does not generally preclude significant E-cadherin expression. They emphasize a link between Snail, Slug, and lymph node metastasis in a large sampling of mammary carcinomas, and suggest a role for Slug in the maintenance of semidifferentiated structures. Snail and Slug proteins seem to support distinct tumor invasion modes and could provide new therapeutic targets.

Animals↗
PubMed2006

Impact of RNA degradation on gene expression profiles: assessment of different methods to reliably determine RNA quality.

DNA microarray technology enables investigators to measure the expression of several 1000 mRNA species simultaneously in a biological specimen. However, the reliability of the microarray technology to detect transcriptional differences representative of the original samples is affected by the quality of the extracted RNA. Thus, it is of critical importance to standardize sample-handling protocols and to perform a quality assessment of RNA preparations. In this report, 59 human tissue samples were used to evaluate the relationships between RNA quality and gene expression. From Affymetrix GeneChip array data analysis of these samples, we compared the performance of the 28S/18S ratio, two computer methods (RIN and degradometer) and our in-house RNA quality scale (RQS) in assessing RNA quality. The optimal RNA reliability threshold was determined for each method using statistical discrimination measures. We showed that RQS, RIN and degradometer have a similar capacity to detect reliable RNA samples whereas the 28S/18S ratio leads to a misleading categorization. Furthermore, we developed a new approach, based on clustering analyses of full chip expression, to control RNA quality after hybridization experiments. The combination of these methods, allowing monitoring of RNA quality prior to and after the hybridization experiments, ensured reliable and reproducible microarray data.

Cluster Analysis↗
PubMed2006

Assessment of epidermal growth factor receptor (EGFR) expression in primary colorectal carcinomas and their related metastases on tissue sections and tissue microarray.

Metastatic colorectal carcinomas (CRC) resistant to chemotherapy may benefit from targeting monoclonal therapy cetuximab when they express the epidermal growth factor receptor (EGFR). Because of its clinical implications, we studied EGFR expression by immunohistochemistry on tissue sections of primary CRC (n=32) and their related metastases (n=53). A tissue microarray (TMA) was generated from the same paraffin blocks to determine whether this technique could be used for EGFR screening in CRC. On tissue sections, 84% of the primary CRC and 94% of the metastases were EGFR-positive. When matched, they showed a concordant EGFR-positive status in 78% of the cases. Moreover, staining intensity and extent of EGFR-positive cells in the primary CRC correlated with those observed in the synchronous metastases. On TMA, 65% of the primary CRC, 66% of the metastases, and 43% of the matched primary CRC metastases were EGFR-positive. There was no concordant EGFR status between the primary and the metastatic sites. A strong discrepancy of EGFR status was noted between TMA and tissue sections. In conclusion, EGFR expression measured in tissue sections from primary CRC and their related metastases was found to be similar and frequent, but it was significantly underestimated by the TMA technique.

Adenocarcinoma↗
PubMed2006

[Vascular hepatic injury following neoadjuvant treatment for a cardial adenocarcinoma].

We report a case of a locally advanced cardial adenocarcinoma, occurring in a 48-year-old woman, who underwent concomitant radiotherapy and 5 FU-cis-platin based chemotherapy. Surgical tumor resection was then performed, which incidentally revealed an isolated liver nodule measuring 12 mm. This nodule was histologically characterized by an intense sinusoidal dilatation and a central venular occlusion, similar to that seen in veno-occlusive disease. This lesion was not correlated to any clinical or biological dysfunction and was finally considered as a vascular injury linked to the additive effect of the combined chemotherapy and radiotherapy. This observation illustrates some iatrogenic hepatic side effects, that have been rarely described in digestive cancers and mainly in the case of colo-rectal metastases. Vascular damage may remain histological, as in our case. But one should be aware that vascular injuries could influence hepatic function and regeneration after wide hepatectomy as well as extensive fibrosis.

Adenocarcinoma↗
PubMed2006

RCL2, a new fixative, preserves morphology and nucleic acid integrity in paraffin-embedded breast carcinoma and microdissected breast tumor cells.

Methacarn and RCL2, a new noncrosslinking fixative, were compared to formalin-fixed or frozen tissue samples of the same invasive breast carcinoma and were evaluated for their effects on tissue morphology and immunohistochemistry as well as DNA and RNA integrity. The histomorphology of methacarn- or RCL2-fixed paraffin-embedded tumors was similar to that observed with the matched formalin-fixed tissues. Immunohistochemistry using various antibodies showed comparable results with either fixative, leading to accurate breast tumor diagnosis and determination of estrogen and progesterone receptors, and HER2 status. Methacarn and RCL2 fixation preserved DNA integrity as demonstrated by successful amplification and sequencing of large DNA amplicons. Similarly, high-quality RNA could be extracted from methacarn- or RCL2-fixed paraffin-embedded MCF-7 cells, whole breast tumor tissues, or microdissected breast tumor cells, as assessed by electropherogram profiles and real-time reverse transcriptase-polymerase chain reaction quantification of various genes. Moreover, tissue morphology and RNA integrity were preserved after 8 months of storage. Altogether, these results indicate that methacarn, as previously shown, and RCL2, a promising new fixative, have great potential for performing both morphological and molecular analyses on the same fixed tissue sample, even after laser-capture microdissection, and can open new doors for investigating small target lesions such as premalignant breast lesions.

Breast Neoplasms↗
PubMed2006

Is there an immunohistochemical technique definitively valid in epidermal growth factor receptor assessment?

Immunohistochemistry (IHC) is required for the selection of patients for a monoclonal antibody based targeted treatment with C225 (Erbitux). To validate the usefulness of IHC, the confirmation of assays and scoring systems are mandatory. In an attempt to standardize the immunohistochemical detection of the epidermal growth factor receptor (EGFR), we retrospectively evaluated three commercially available EGFR kits or antibodies and analyzed the discrepancies between the tests in terms of the percentage of positive cells, intensity, cut-off value and fixatives. We extracted 232 paraffin-embedded samples from a metastatic colorectal cancer clinical trial. For all the cases, EGFR expression was assessed with the FDA approved Dako EGFR pharmaDx kit, the Zymed EGFR kit and the Ventana EGFR 3C6 antibody. Different cut-off values were tested, and the intensity was scored 0, 1+, 2+, 3+ following Dako's recommendations. The percentage of positive cases varied from 93 to 75% with a cut-off of value 1% of positive cells, from 80 to 61% with a cut-off of 5% positive cells and from 72% to 48% with a cut-off value of 10%. Both Ventana and Zymed tests were more sensitive than the Dako test (Ventana >Dako; p<10(-7), Zymed >Dako; p=2.10(-6)). No difference was noted between Ventana and Zymed tests (p=0.75). A high concordance was observed for the 3 tests for the evaluation of high intensities. The use of a scoring system combining the percentage of positive cells and intensity was not useful for Zymed and Ventana as the intensity of staining is correlated to the percentage of positive cells: Ventana (p<10(-6)) and Zymed (p<10(-5)). No interaction with staining was identified for any of the fixatives, or with the nature of samples received (i.e. slides vs blocks, biopsies vs surgical specimens). Our data showed a higher percentage of positive cells detected by Ventana and Zymed tests, whatever the cut-off value for positivity. No scoring system showed, to date, its accuracy, and more studies have to be conducted with an evaluation of the response to cetuximab, possibly with a correlation with FISH amplification in colorectal carcinoma.

Adenocarcinoma↗
PubMed2005

[Recent data on lobular neoplasia of the breast: the pathologist's opinion].

Lobular neoplasia is the new WHO terminology that encompasses the so-called lobular carcinoma in situ and atypical lobular hyperplasia. Besides the classical forms, particular variants have been described, which are mammographically detectable with distinct histologic patterns and behaviour. These variants are characterized by pleomorphic cells, necrosis with calcifications and may be associated to an invasive lobular carcinoma. Their clinical issue looks more like a preinvasive lesion than a marker of increased risk. Thus, their identification on biopsy requires a surgical reexcision. Hybrid forms, sharing a mixed lobular and ductal morphology and phenotype, have also been mentionned. Despite a lack of prognostic evaluation, it seems logical to recommend a subsequent surgical investigation when they are observed. Classical forms are usually managed by simple follow-up, although this attitude does not make a consensus among pathologists. Lobular neoplasia are not all indolent lesions and belong to an heterogeneous group that percutaneous guided biopsies have emphasized. They should be managed in a pluridisciplinar way and correctly diagnosed on percutaneous biopsies as well as surgical specimens.

Biopsy↗
PubMed2005

Comprehensive profiling of 8p11-12 amplification in breast cancer.

In human carcinomas, especially breast cancer, chromosome arm 8p is frequently involved in complex chromosomal rearrangements that combine amplification at 8p11-12, break in the 8p12-21 region, and loss of 8p21-ter. Several studies have identified putative oncogenes in the 8p11-12 amplicon. However, discrepancies and the lack of knowledge on the structure of this amplification lead us to think that the actual identity of the oncogenes is not definitively established. We present here a comprehensive study combining genomic, expression, and chromosome break analyses of the 8p11-12 region in breast cell lines and primary breast tumors. We show the existence of four amplicons at 8p11-12 using array comparative genomic hybridization. Gene expression analysis of 123 samples using DNA microarrays identified 14 genes significantly overexpressed in relation to amplification. Using fluorescence in situ hybridization analysis on tissue microarrays, we show the existence of a cluster of breakpoints spanning a region just telomeric to and associated with the amplification. Finally, we show that 8p11-12 amplification has a pejorative effect on survival in breast cancer.

Breast Neoplasms↗
PubMed2005

[EGFR expression in colorectal cancer and role in tumorigenesis].

Epithelial growth factor receptor (EGFR) appears as a key element in colorectal carcinogenesis. It displays high levels of expression. Its activation induces cell proliferation, angiogenesis, cell mobility and inhibition of apoptosis. EGFR inhibitors such as monoclonal antibodies or small molecules tyrosine kinase inhibitors have been developed. For EGFR, the diversity of the activation means (amplification, mutation, enhanced transcription, ligands...) leads to technical caveats. Pathologists are involved in the selection of patients for a monoclonal antibody based targeted treatment, Erbitux (cetuximab), and numerous standardization efforts are provided. No consensus has been reached, to date, for a scoring system for immunohistochemistry. No correlation has been found so far between EGFR level of expression and response to cetuximab. Whether and how the EGFR status has to be tested for the selection of patients is a non answered question. The selection of the "right patient for the right treatment" might be through the evaluation of other putative markers involved in resistance. EGFR testing may be required before targeted treatment. An exciting endpoint might be the functional and dynamic evaluation of EGFR and downstream proteins for patients, before and during treatment.

Colorectal Neoplasms↗
PubMed2004

Roles of the transcription factors snail and slug during mammary morphogenesis and breast carcinoma progression.

The zinc-finger transcription factors Snail and Slug are involved in different processes controlling cell differentiation and apoptosis. They also appear to be involved in tumor progression. Their putative involvement in mammary gland development has not been specifically examined so far. Slug is expressed at a significant level in normal breast, and indirect evidence suggests it could be implicated in tubulogenesis. As an antiapoptotic agent, it could also protect epithelial cells from death during ductal lumen formation and during breast involution. In breast carcinomas, Snail transcription factors have been linked to tumor progression and invasiveness. Possible mechanisms include repression of the E-cadherin gene by Snail or Slug. However, it is not clear how this transcriptional activity is implicated in vivo. Other possible mechanisms involve maintenance of a plastic phenotype by Slug that could participate in local invasion of ductal carcinomas, and interference with apoptotic pathways that could contribute to global tumor growth and radioresistance. These processes probably also involve interactions with estrogen, EGF, or c-kit pathways.

Animals↗
PubMed2003

[Management of non-palpable breast lesions with vacuum-assisted large core needle biopsies (Mammotome). Experience with 560 procedures at the Val d'Aurelle Center].

Percutaneous vacuum-assisted large core needle biopsy of breast microcalcifications is now commonly performed as the initial approach to nonpalpable breast lesions. It can obviate the need for surgery in women with benign lesions and often lead to a one-stage surgical procedure when malignant lesions are diagnosed. To illustrate this strategy, we describe our experience based on 560 procedures performed within a 36 Month-period. Sixty percent of the lesions were benign, mostly fibrocystic changes. Thirty percent of the specimens were malignant, almost exclusively intraductal carcinomas, sometimes associated with an invasive component. This component must be identified by the pathologist in order to avoid incomplete treatment and to plan lymph node excision. Finally, 10% of the specimens were boderline including lobular neoplasia, atypical ductal hyperplasia and columnar cell lesions with atypia. Surgical excision is recommended for atypical ductal hyperplasia, columnar cell lesions with atypia and lobular neoplasia with particular features, pleomorphic or comedo-like, to avoid missing more aggressive associated lesions. A strict procedure is required for the analysis of needle core biopsies and the subsequent surgical specimens, to accurately classify breast lesions provided by a mammographic screening program. This procedure should be based on a multidisciplinary approach and dialog.

Biopsy, Needle↗