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BackgroundThe prognostic value of the primary neoplasm responsible for pseudomyxoma peritonei (PMP) remains poorly studied. The aim of this study was to determine the prognosis for patients with extra-appendicular PMP (EA-PMP) treated optimally with complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsAll patients treated for PMP with CCRS and HIPEC between 1994 and 2016 were selected retrospectively from a French multicentre database. Patients with EA-PMP had pathologically confirmed non-neoplastic appendices and were matched in a 1 : 4 ratio with patients treated for appendicular PMP (A-PMP), based on a propensity score.ResultsSome 726 patients were identified, of which 61 (EA-PMP group) were matched with 244 patients (A-PMP group). The origins of primary tumours in the EA-PMP group included the ovary (45 patients), colon (4), urachus (4), small bowel (1), pancreas (1) and unknown (6). The median peritoneal carcinomatosis index was comparable in EA-PMP and A-PMP groups (15·5 versus 18 respectively; P = 0·315). In-hospital mortality (3 versus 2·9 per cent; P = 1·000) and major morbidity 26 versus 25·0 per cent; P = 0·869) were also similar between the two groups. Median follow-up was 66·9 months. The 5-year overall survival rate was 87·8 (95 per cent c.i. 83·2 to 92·5) per cent in the A-PMP group and 87 (77 to 96) per cent in the EA-PMP group. The 5-year disease-free survival rate was 66·0 (58·7 to 73·4) per cent and 70 (53 to 83) per cent respectively.ConclusionOverall and disease-free survival following treatment with CCRS and HIPEC is similar in patients with pseudomyxoma peritonei of appendicular or extra-appendicular origin.

Background Epithelioid peritoneal malignant mesothelioma (EPMM) is the most common subtype of this aggressive tumor. We compared two antibodies against PD-L1, a recent theranostic biomarker, and evaluated the prognostic value of PD-L1 expression by mesothelial and immune cells in EPMM. Methods Immunohistochemistry was performed on 45 EPMM. Clinical and pathological data were extracted from the RENAPE database. Using E1L3N and SP142 clones, inter-observer agreement, PD-L1 expression by mesothelial and immune cells and inter-antibody agreement were evaluated. The prognostic relevance of PD-L1 expression was evaluated in 39 EPMM by univariate and multivariate analysis of overall survival (OS) and progression-free survival (PFS). Results Inter-observer agreement on E1L3N immunostaining was moderate for mesothelial and immune cells, and fair for mesothelial and poor for immune cells using SP142. Using E1L3N, 31.1% of mesothelial and 15.6% of immune cells expressed PD-L1, and 22.2% of mesothelial and 26.7% of immune cells using SP142. Inter-antibody agreement was moderate. In most positive cases, 1–5% of tumor cells were positive. Using E1L3N, PD-L1 expression by lymphocytes was associated with better OS and PFS by both univariate and multivariate analysis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy predicted better prognosis than other treatments. Solid subtype was an independent prognostic factor for worse OS. Conclusion E1L3N appeared easier to use than SP142 to evaluate PD-L1 expression. A minority of EPMM expressed PD-L1, and only a few cells were positive. PD-L1 expression by immune cells evaluated with E1L3N was an independent prognostic factor in EPMM.

Purpose: Diffuse malignant peritoneal mesothelioma (DMPM) is a severe disease with mainly locoregional evolution. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the reported treatment with the longest survival. The aim of this study was to evaluate the impact of perioperative systemic chemotherapy strategies on survival and postoperative outcomes in patients with DMPM treated with curative intent with CRS-HIPEC, using a multi-institutional database: the French RENAPE network. Patients and methods: From 1991 to 2014, 126 DMPM patients underwent CRS-HIPEC at 20 tertiary centres. The population was divided into four groups according to perioperative treatment: only neoadjuvant chemotherapy (NA), only adjuvant chemotherapy (ADJ), perioperative chemotherapy (PO) and no chemotherapy before or after CRS-HIPEC (NoC). Results: All groups (NA: n Z 42; ADJ: n Z 16; PO: n Z 16; NoC: n Z 48) were comparable regarding clinicopathological data and main DMPM prognostic factors. After a median follow-up of 61 months, the 5-year overall survival (OS) was 40%, 67%, 62% and 56% in NA, ADJ, PO and NoC groups, respectively (P Z 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (P Z 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07e4.94; P Z 0.033). Conclusion: This retrospective study suggests that adjuvant chemotherapy may delay recurrence and improve survival and that NA may impact negatively the survival for patients with DMPM who underwent CRS-HIPEC with curative intent. Upfront CRS and HIPEC should be considered when achievable, waiting for stronger level of scientific evidence.

Objectif Le curage lombo-aortique est le traitement curatif chirurgical de reference des masses residuelles dans le cancer du testicule. Le curage doit comporter la totalite du tissu lymphatique au sein d’un volume precis. Les territoires de curage dependent de la localisation de la masse residuelle et les techniques chirurgicales ont ete revues pour diminuer la morbidite de cette intervention. Methodes Nous rapportons un cas de curage lombo-aortique radical modifie droit pour masse residuelle persistante apres chimiotherapie dans le cadre d’une tumeur testiculaire. Patient opere en 2018. Le territoire de curage presente comme limite superieure les veines renales, en limite laterale le pedicule spermatique droit, en limite mediale la face anterieure de l’aorte jusqu’a l’emergence de l’artere mesenterique inferieure, puis le bord droit de l’aorte jusqu’a sa bifurcation iliaque. La limite inferieure est la bifurcation iliaque interne/externe. L’intervention s’est deroulee par cœlioscopie avec abord extra peritoneal. Resultats Patient de 20 ans opere en juin 2018 d’un orchidectomie droite pour tumeur testiculaire. L’examen anatomo-pathologique rapportait une tumeur germinale non seminomateuse mixte associant du seminome, du carcinome embryonnaire et du carcinome vitellin. Le stade TNM etait pT1N2M0S2. A la fin de la chimiotherapie, le scanner de controle montrait la persistance d’une masse residuelle ganglionnaire inter aortico-cave de 11 × 10 mm. Apres discussion en RCP, indication de curage lombo-aortique radical modifie droit. Cette intervention s’est deroulee par voie laparoscopique avec abord extra peritoneal. Les suites operatoires ont ete simples. Le drain chirurgical retire au 4e jour post-operatoire. L’analyse histologique ne retrouvait pas de ganglion pathologique. Le scanner de controle realise a 2 mois post-operatoire ne retrouvait aucun signe evolutif de la pathologie. Conclusion Le curage lombo-aortique est une intervention chirurgicale avec une grande morbidite. Cette morbidite est due aux lesions realisees lors de l’intervention des fibres nerveuses sympathiques du plexus hypogastrique. Ces lesions sont responsables de troubles de l’ejaculation. Afin de minimiser ces lesions, des strategies d’epargne nerveuse comme le curage unilateral modifie ont ete developpees tout en etant oncologiquement valides.

Breast cancer is the most frequent female cancer with 48 800 new cases each year in France. A French national screening program in women without genetic risk factors has been initiated in 2004. Women with BRCA 1 or 2 mutations are included in surveillance programs. Women without such mutations can be assessed for breast cancer risk using risk prediction models. The aim of this study is to compare the performance of three breast cancer risk prediction models: GAIL2, BODICEA and IBIS in a population of patients (pts) who developed breast cancer. Patients and Methods: The GAIL1 model was performed to 188 pts at high risk of breast cancer according to their family history and who developed breast cancer. Personal and familial data was regenerated at the day before the diagnosis of breast cancer and the three models were applied. From this population, 60 pts were selected: for whom all information necessary to use the 3 models was available and for whom the GAIL1 model provided sufficient variability in the relative risk of breast cancer. The GAIL2 model takes into account individual risk factors: age, menarches, parity, age at first birth, history of breast biopsy, atypical hyperplasia or in situ lobular carcinoma. The BODICEA model considers age and familial risk factors: number of related affected by breast ovarian, prostate and pancreas cancer and age at diagnosis. Both personal and familial risk factors are used for the IBIS model. We estimated lifetime breast cancer risk for each patient with the three models from the available software packages. We assessed Pearson's correlation coefficient between the three models. Results Median (range) age was 45 years (25-74). Risk prediction could not be evalauted by the GAIL2 model for 14 pts since they were less than 35 years of age. Lifetime breast cancer risk was 16.1% (4.4-38.7) for GAIL2, 11.6% (2.2-39.5) for BODICEA and 16.5% (3.5-36.3) for IBIS. Pearson's correlation coefficient between BODICEA and GAIL2, IBIS and GAIL2 and between BODICEA and IBIS were 0.36, 0.38 and 0.69 respectively. In most cases, IBIS risk predictions were higher than GAIL2's which were higher than BODICEA's as soon as lifetime risk was at least 20%. When the three models were applicable (46pts), IBIS estimated a higher risk in 31 cases (67%) versus 10 for GAIL2 (21.74%) and 5 for BODICEA (10.86%). The median (range) time for use of the tools per patient was 30 seconds (16-80) for GAIL2, 588 (198-1804) for BODICEA and 86 (46-135) for IBIS. Discussion Results in this selected population of pts who developed breast cancer show that IBIS seems to be the better performer to predict breast cancer risk:. Results are obtained faster and the risk predictions provide higher estimates. The GAIL2 model is quick and easy to use but with a limited number of items. Conversely, BODICEA requires a very large number of items, not always available, and does not consider incomplete data. In conclusion, IBIS model seems to be the most suitable for practical use in the evaluation of breast cancer risk. Citation Format: Mailliez A, Kramar A, Peyrat J-P, Revillion F, Bonneterre J. Comparison of prediction models of breast cancer in high risk populations?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-16.

Background: Adjuvant chemotherapy (ACT) using anthracyclines and taxanes is a standard treatment for BC. Usual criteria as age, SBR grade, HER2 or hormonal status (HS), estrogen receptor (ER), triple negative BC, histological type, lymphovascular invasion (LVI), Ki67, tumor size and lymph node involvement are not yet sufficient for ACT decision. As SNPs located in genes involved in metabolism or transport of cytotoxic drugs may affect efficacy of ACT, we investigated the potential of 49 SNPs to predict response to ACT in BC. Methods: From 01/2008 to 01/2012, 418 patients (pts) with BC treated with ACT were included. 309 pts received FEC100-Docetaxel regimen (cohort 1), and 109 pts with HER2 overexpression FEC100-Docetaxel-Trastuzumab regimen (cohort 2). Genotyping of 49 SNPs was performed on germline DNA using real time PCR with SNPType (Fluidigm) or Taqman probes (Life technologies) on BioMark Platform (Fluidigm). PFS, MFS and overall survival (OS) were estimated by Kaplan-Meier method. Association of clinicopathologic features (CPF) with PFS/MFS was evaluated by log-Rank test. After ensuring Hardy-Weinberg equilibrium was respected, PFS/MFS were correlated to CPF and genotypes, using univariate and multivariate Cox logistic regression. A prognostic score was established. Results: PFS, MFS and OS rates were respectively 81.8%, 83.4% and 87.3% in cohort 1 (3.4 years of median follow up (FU)) and 90.1%, 90% and 93.8% in cohort 2 (4 years of FU). In cohort 1, univariate analysis revealed that 5 SNPs, SLCO1B3 (rs11045585), NOS3 (rs1799983), CYB2B6 (rs2279345), BRCA1 (rs799917) and CYP2D6 (rs3892097) were associated with MFS. Genotypes, HR, 95%CI and p value are as follows: SLCO1B3 GG 7.73 (1.83-32.7) p=0.001, NOS3 GT 0.32 (0.14-0.76) p=0.006, CYB2B6 TT 2.29 (1.02-5.13) p=0.04, BRCA1 CT 0.41 (0.19-0.89) p=0.02, and CYP2D6 AG 2.14 (1.05-4.36) p=0.03. Multivariate analysis revealed that 4 SNPs remained associated with metastatic risk: CYB2B6; TT 2.38 (1.05-5.41) p=0.038, NOS3; GG-TT 3.11 (1.33-7.27) p=0.009, BRCA1; CC-TT 2.21 (1.01-4.85) p=0.047, CYP2D6; AG 2.14(1.04-4.40) p=0.039. No CPF was associated with survival. Prognostic model revealed a metastatic risk of 10.25 (1.29-81.31) if these four adverse genotypes coexist. In cohort 2, subject to limited number of events, age (p=0.03), HS (p=0.06), ER (p=0.05), LVI (p=0.02) tumor size (p=0.003) and 2 SNPs were associated in univariate with PFS: CYB2B6 (rs2279345); CT 5.73 (1.22-27) p=0.01, MTHFR (rs1801133); CT 4.61 (0.98-21.7) p=0.03. Multivariate analysis showed unfavorable PFS for heterozygous patients for CYB2B6 or for MTHFR: 9.67 (1.82-51.28) p=0.008 and 5.62(1.19-26.59) p=0.03 respectively and if tumor size was ≥T2 10.78 (2.12-54.90) p=0.004. Conclusion: SNPs of genes involved in oxidative stress (NOS3 rs1799983; GG-TT), docetaxel transport (SLCO1B3 rs11045585; GG) cyclophosphamide (CYB2B6 rs2279345; TT in cohort 1 ou CT in cohort 2) and 5FU metabolism (MTHFR rs1801133; CT), or DNA repair (BRCA1rs799917; CC-TT) are associated with survival in pts treated with ACT. BRCA1, CYB2B6 and SLCO1B3 represent potential attractive tools for guiding ACT indication. Citation Format: Ducoulombier A, Dumont A, Revillion F, Bonneterre J, Peyrat J-P. Evaluation of single nucleotide polymorphisms (SNPs) as predictive factors of progression (PFS) and metastatic (MFS) free survival in adjuvant breast cancer (BC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-24.

CONTEXT AND AIMS:Breast cancer prognosis and predictive biomarkers development would allow sparing some patients from chemotherapy or identifying patients for whom chemotherapy would be indicated. In this context, in 2009, the French National Cancer Institute, a National Health and Science Agency dedicated to cancer, in collaboration with the French society of senology and breast pathology (SFSPM) published a report on the assessment of the prognostic and the predictive clinical validity of tissular biomarkers, uPA/PAI-1, Oncotype DX™ and MammaPrint(®), in breast cancer management. They concluded that only the uPA/PAI-1 prognosis value reached the highest level of evidence (LOE I according to Hayes 1998 classification). In 2012, it was decided to update this report since new data have emerged and because information disparities among clinicians have been identified. This article aims to present the main conclusions together with the levels of evidence associated with those conclusions.METHODS:The updating process was based on literature published since 2009 appraisal and on multidisciplinary and independent experts' opinion. The levels of evidence (LOE) used are those of the classification defined by Simon in 2009 (updated Hayes 1998 classification): LOE IA and LOE IB: high level of evidence; LOE IIB and LOE IIC: intermediate level of evidence; LOE IIIC and LOE IV-VD: low level of evidence.CONCLUSIONS:Among patients without lymph-node involvement, uPA/PAI-1, invasion process biomarkers, reach the highest level of evidence for 10 years recurrence free survival prognosis (LOE IA according to Simon). The predictive value to anthracyclins chemotherapy remains to be confirmed. Oncotype DX™ and MammaPrint(®) prognosis and predictive value do not reach the LOE I level. This updating' process confirms the 2009 levels of evidence for all the three biomarkers prognosis value. Besides, concerning Oncotype DX™ and MammaPrint(®), new data do not allow to conclude neither to their complementary clinical information to other clinicopathological existing biomarkers nor to a favorable cost-efficiency ratio in therapeutic decision making and this because of the methodological weakness and uncertainty that are identified in the selected studies. Practically, beyond the prognosis and predictive biomarkers validity, the clinical utility of a new biomarker for chemotherapy indication depends on its clinical added information with regard to validated biomarkers (HR, HER2 and Ki67) and to clinicopathological parameters. Since they are the sole validated biomarkers of the invasion process, uPA/PAI-1 could complete clinical information of other clinicopathological factors and consequently could confer an added clinical value. However, data concerning the impact of this information on chemotherapy clinical indication are lacking.Copyright © 2014. Published by Elsevier Masson SAS., IntroductionDans le cancer du sein, le développement des marqueurs biologiques pronostiques ou prédictifs a pour objectif de mieux identifier les patientes pour lesquelles un traitement par chimiothérapie pourrait être évité ou a contrario indiqué. Dans ce contexte, en 2009, l’Institut national du cancer (INCa), agence sanitaire et scientifique de l’État chargée de coordonner les actions de lutte contre le cancer, avait publié en partenariat avec la Société française de sénologie et de pathologie mammaire un rapport sur l’état des connaissances relatives aux biomarqueurs uPA/PAI-1, Oncotype DX™ et MammaPrint® dans la prise en charge du cancer du sein. Ce rapport avait montré que seule la valeur pronostique d’uPA/PAI-1 atteignait le plus haut niveau de preuve (LOE I selon la grille de Hayes 1998). En 2012, devant la parution de nouvelles publications et la divergence des messages diffusés sur les signatures moléculaires, il a été décidé d’actualiser le rapport de 2009. Cet article présente les principales conclusions accompagnées de leurs niveaux de preuve.MéthodeLe processus de mise à jour s’est appuyé sur l’analyse des données publiées depuis la recherche bibliographique de 2009, complétée par l’avis d’un groupe de travail multidisciplinaire indépendant. Les niveaux de preuve employés sont ceux de la classification définie par Simon en 2009 (grille de Hayes 1998 après mise à jour) : LOE IA et LOE IB : niveau de preuve élevé ; LOE IIB and LOE IIC : niveau de preuve intermédiaire ; LOE IIIC and LOE IV-VD : niveau de preuve faible.ConclusionsChez les patientes sans envahissement ganglionnaire (pN0), uPA/PAI-1, marqueurs d’invasion, ont un niveau de preuve élevé (LOE IA selon Simon) pour la valeur pronostique de la survie sans récidive à 10 ans. Il reste à confirmer leur valeur prédictive de réponse aux anthracyclines. Pour Oncotype DX™ et MammaPrint®, les valeurs pronostique et prédictive n’ont pas atteint à ce jour le niveau de preuve LOE I. Ce travail confirme les niveaux de preuve précédemment établis dans le rapport de 2009. Par ailleurs, les données ne permettent pas de conclure à une valeur ajoutée de Oncotype DX™ et MammaPrint® par rapport aux outils existants. Les données médico-économiques ne permettent pas de statuer sur le rapport coût/efficacité des stratégies utilisant ces tests dans la décision thérapeutique compte tenu d’un niveau de qualité insuffisant pour la plupart des études et d’une forte incertitude mise en évidence par les quelques études bien menées. En pratique, au-delà des niveaux de preuve attribuables à la valeur pronostique et prédictive d’un biomarqueur, l’utilité clinique d’un nouveau marqueur dans l’aide à la prescription d’une chimiothérapie repose sur sa valeur ajoutée par rapport aux marqueurs validés (RH, HER2 et les marqueurs de prolifération comme Ki67) et aux critères anatomo-cliniques. Puisqu’ils sont les seuls marqueurs validés à témoigner du processus d’invasion, uPA/PAI-1 peuvent apporter une information complémentaire et donc avoir une valeur ajoutée par rapport aux marqueurs existants. Les données de la littérature manquent pour apprécier le poids de cette valeur ajoutée dans la décision de prescrire ou non une chimiothérapie.

Background Retroperitoneal nodal metastases (RNM) represent 1–2% of metastases from colorectal cancer (CRC). Non-surgical treatments achieve 5-year overall survival (OS) of 0–12%. Radical retroperitoneal lymphadenectomy (RRL) in this setting remains controversial, but most published series do not distinguish local retroperitoneal recurrences from RNM. We specifically report outcomes after RRL for RNM from CRC. Methods We analyzed prospectively recorded data from patients who underwent standardized RRL for RNM from CRC between January 1997 and August 2012 in our institution. Local retroperitoneal recurrences were excluded. Results Twenty-five patients underwent RRL for synchronous (n = 19) or metachronous (n = 6) RNM from CRC. Fifteen patients had extra-retroperitoneal metastases. Median hospital stay was 16 [7–23] days. Grade ≥ III morbidity was 8% with no perioperative deaths. Median follow-up was 85 [4–142] months. Median OS and progression free survival (PFS) were 60 [4–142] and 14 [1–116] months. One, three- and 5-year OS were 92%, 64% and 47%. One, three- and 5-year PFS were 51%, 26% and 26%. Retroperitoneal nodal metastases from stage III CRC were associated with better median OS compared to those from stage IV CRC (p = 0.02). This variable did not impact on PFS. Subject to substantial risk of type II error on small samples data statistical analysis, survivals were not affected by timing and location of RNM, extra-retroperitoneal metastasis, nodal disruption, neoadjuvant nor adjuvant chemotherapy. Conclusions To our knowledge, this is the largest series yet reported which specifically studied outcomes of RRL for RNM from CRC. RRL allows favorable outcomes in selected patients with acceptable morbidity.

Introduction Peritoneal metastasis (PM) of hepatocellular carcinoma (HCC) without distant spread are rare. The related prognosis is poor without standard treatment available. The role of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly documented. Methods An international multicentric cohort was constituted by retrospective analysis of 21 patients undergoing CRS/HIPEC for PM of HCC between 1992 and 2016 from 10 reference centers of PSOGI. Data on clinical features, treatment strategies, and survival outcomes were analyzed. Results The median time interval from the diagnosis of PM to the procedure was 4.5 months. The median peritoneal cancer index was 14. Sixteen patients had complete cytoreduction (CCR0-1). Ten patients had grades 3 to 4 complications. The median duration of follow-up was 52.2 months. The median OS was 46.7 months. The projected 3y-OS and 5y-OS were 88.9 and 49.4% respectively. The median OS for patients with CCR0-1 resection was not reached whereas it was 5.9 months for those with CCR2-3 resection after CRS (p = 0.0005). The median RFS was 26.3 months and projected RFS at 3 years of 36.5 months Three prognostic factors were associated with improved RFS in the univariate analysis: preoperative chemotherapy (p = 0.0156), PCI >15 (p = 0.009), Number of chemotherapy agents used for HIPEC (p = 0.005). Conclusion CRS/HIPEC is a safe and effective approach in selected patients with PM of HCC. CRS/HIPEC gives the patient a chance for a good relapse free and overall survival and should be considered as an option.

Objectif Dans les tumeurs germinales non seminomateuses du testicule (TGNS), la chirurgie des masses ganglionnaires residuelles apres chimiotherapie est necessaire, en cas de masses superieures a 1 cm. Le curage ganglionnaire lombo-aortique bilateral complet est recommande, mais un curage unilateral modifie peut etre propose pour des masses residuelles de faibles volumes, dans une strategie d’epargne nerveuse, afin de limiter les troubles de l’ejaculation. Methodes Cette video illustre le cas d’un homme de 38 ans presentant une TGNS du testicule droit, classee pT2N2M0S1, de bon pronostic, avec une adenopathie inter aortico-cave de 25 mm. Il a eu une chimiotherapie par 3 cures de BEP (Bleomycine, Etoposide et Cisplatine). Les marqueurs tumoraux se sont normalises apres 2 cures de BEP. Le scanner de reevaluation met en evidence la persistance d’une adenopathie inter aortico-cave de 14 mm. Le patient a ete opere d’un curage ganglionnaire unilateral modifie droit. Resultats Installation en decubitus dorsal. Une laparotomie mediane xypho-pubienne est pratiquee. On expose l’espace retro-peritoneal en decollant la racine du mesentere. On repere les limites du curage : uretere droit (laterale), pedicules renaux (superieure), bifurcation iliaque (inferieure), ligament commun vertebral posterieur (posterieure). On retire tous les elements ganglionnaires latero-cave, pre-cave, retro-cave et inter aortico-cave, de la bifurcation iliaque aux veines renales. On retire les tissus lymphatiques pre-aortiques, uniquement dans le territoire au-dessus de l’artere mesenterique superieure, jusqu’aux pedicules renaux, en preservant l’adventice arteriel. On reseque en totalite le pedicule spermatique droit, jusqu’a l’orifice inguinal profond. Les suites ont ete simples, le patient sort a J3 apres ablation du drain. L’analyse histologique a mis en evidence du teratome au niveau de la masse inter aortico-cave. Conclusion Un curage unilateral modifie peut-etre propose pour diminuer la morbidite post-operatoire. L’interet de cette video est de presenter anatomiquement les limites du curage et la conservation de l’adventice arteriel, afin de preserver les fibres nerveuses du plexus hypogastrique.

In digestive cancers, the prognostic significance of intraperitoneal free cancer cells remains unclear (IPCC). The main objective of this study was to assess the prognostic significance of IPCC in colorectal and gastric adenocarcinoma. The secondary objectives were to evaluate the predictive significance of IPCC for the development of peritoneal carcinomatosis (PC) and to evaluate the prevalence of synchronous PC and IPCC.This was a prospective multicentre study. All patients undergoing surgery for a digestive tract cancer had peritoneal cytology taken. Patients with gastric and colorectal cancer with no residual tumour after surgery and no evidence of PC were followed-up for 2 years. The primary end point was overall survival.Between 2002 and 2007, 1364 patients were enrolled and 956 were followed-up over 2 years. Prevalence of IPCC was 5.7% in colon cancer, 0.6% in rectal cancer and 19.5% in gastric cancer. The overall 2-year survival rate for patients with IPCC was 34.7% versus 86.8% for patients with negative cytology (p0.0001). By multivariate analysis, IPCC was not an independent prognostic factor. No relationship between cytology and recurrence was found.The presence of IPCC was not an independent prognostic and didn't add any additional prognostic information to the usual prognostic factors related to the tumour (pTNM and differentiation). Moreover the presence of IPCC detected with this method didn't appear to predict development of PC. Peritoneal cytology using conventional staining doesn't seem to be a useful tool for the staging of colorectal and gastric cancers.

Resume Introduction La radionecrose cutanee et l’osteoradionecrose sont des complications graves de la radiotherapie pouvant survenir apres un intervalle libre variable. La perte de substance associee frequemment a une radiodermite peripherique reste une porte d’entree infectieuse exposant la patiente a un sepsis. Le traitement de reference reste chirurgical et consiste a realiser un parage–lavage de la perte de substance associe a un geste de couverture par des tissus bien vascularises. Le but de notre etude est d’evaluer l’efficacite et la tolerance du resurfacage par le lambeau avec preservation partielle du latissimus dorsi ou PPLD. Patientes et methodes Nous avons realise une etude sur une serie de cas de radionecroses thoraciques avec exposition costale necessitant une couverture par lambeau avec preservation partielle du latissimus dorsi. Un transfert graisseux dans les tissus radiques peripheriques a ete realise dans le meme temps chirurgical. L’efficacite et la tolerance de la chirurgie ont ete evaluees. La duree de l’antibiotherapie postoperatoire a ete evaluee. Les complications (hematome, infection, souffrance cutanee, necrose de lambeau, serome, recidive de la radionecrose) ont ete evaluees. Le suivi a ete realise par le meme chirurgien. Resultats Sept patientes ont ete incluses dans l’etude, toutes prises en charge par le meme chirurgien. L’indication a ete la couverture d’une radionecrose thoracique severe secondaire a de la radiotherapie pour traitement adjuvant de la mastectomie apres cancer du sein. L’âge moyen etait de 66 ans (allant de 61 a 76 ans). La duree moyenne d’hospitalisation etait de quatre jours. Le suivi moyen etait de six mois apres l’intervention. La duree moyenne de l’antibiotherapie a ete de quatre semaines. Aucune complication n’a ete notee. Une ponction d’un serome dorsal (30 cm 3 ) a ete realisee a 15 jours postoperatoires pour une patiente. Le suivi a montre une couverture cutanee stable et de bonne qualite a six mois postoperatoire. Conclusions Le lambeau pedicule avec preservation partielle du latissimus dorsi (PPLD) est fiable et reproductible pour assurer la couverture d’une radionecrose cutanee thoracique moderee. Le parage-lavage chirurgical a une importance fondamentale pour eviter toute complication infectieuse. La prise en charge de la radionecrose thoracique est complexe et multidisciplinaire. En conclusion, le lambeau PPLD constitue une alternative chirurgicale elegante assurant une couverture optimale sur mesure avec une reduction de la morbidite du site donneur.

A pathological complete response (pCR) after neoadjuvant chemotherapy is observed in approximately 20% of breast cancer patients. A proteomic analysis was performed on plasma and tumor tissue before treatment to evaluate its potential impact on the prediction of response. One hundred and forty-nine breast cancer patients eligible for neoadjuvant chemotherapy were included in the study between February 2004 and January 2009 at three centers. The proteomic analysis was performed using SELDI Technology (ProteinChip CM10 pH4, IMAC-Cu and H50). Three acquisition protocols were used according to the mass range. Plasma and tumor proteomic signatures were generated using generalized ROC criteria and cross-validation. Twenty-eight (18.8%) patients out of 149 experienced a pCR according to Sataloff criteria. In the cytosol analysis, respectively 4, 2 and 8 proteins had significantly different levels of expression in the responders and non-responders using IMAC-Cu, H50 and CM10 pH4. Among the 8 proteins of interest on CM10 pH4, 2 (C1 and C7) were selected and were validated in 95.0 and 85.6% of the models. In the plasma analysis, respectively 12, 6 and 2 proteins had different levels of expression using the same proteinchips. Among the 12 plasma proteins of interest on IMAC-Cu, 2 (P1 and P7) were selected and were validated in 94.8 and 97.6% of the models. A combined proteomic signature was generated, which remained statistically significant when adjusted for hormone receptor status and Ki-67. Our results show that proteomic analysis can differentiate complete pathological responders in breast cancer patients after neoadjuvant chemotherapy.

Les liens entre obesite et cancer du sein pourraient resulter de l’action d’adipokines produites par les cellules adipeuses. Parmi ces adipokines, la leptine semble jouer un role important. La presence de ses recepteurs sur les cellules de cancers du sein montre qu’elle peut agir directement sur ces cellules: elle est de fait capable de stimuler leur proliferation. Les voies d’action empruntees sont endocrine, paracrine et autocrine. De plus, la leptine serait capable de s’opposer aux traitements anti-estrogeniques. Ces observations suggerent que le blocage de la leptine aurait un interet therapeutique dans les cancers du sein.

Background The aim of this study is to provide an expression profile of ErbB/HER ligands in breast cancer. We analysed the relationships with their receptors, the bio-pathological features and prognosis. Patients and methods Epidermal growth factor (EGF), transforming growth factor-α (TGFα), amphiregulin (AREG), betacellulin (BTC), heparin-binding EGF-like growth factor (HB-EGF), epiregulin (EREG) and neuregulins1–4 (NRG1–4) were quantified in 363 tumours by real-time reverse transcription–polymerase chain reaction using TaqMan probes. Results Ligands were detected in 80%–96% of the cases, except NRG3 (42%) and EREG (45.5%). At least one ligand was expressed in 304 cases (cut-off: upper quartile). Almost all combinations of receptor and ligand co-expressions were observed, but TGFα is preferentially expressed in tumours co-expressing EGFR/HER3, NRG3 in those co-expressing EGFR/HER4, AREG and EREG in those co-expressing HER2/HER4. EGF and AREG were associated with estradiol receptors, small tumour size, low histoprognostic grading, high HER4 levels. TGFα, HB-EGF and NRG2 were negatively related to these parameters. In Cox univariate analyses, EGF was a prognostic factor. Conclusion Our study demonstrates that (i) ErbB/HER ligands, including BTC and EREG, are expressed in most breast cancers; and (ii) TGFα, HB-EGF and NRG2 high expressions are related to the biological aggressiveness of the tumours.

International audience; Based on the importance of assessing the true extent of peritoneal disease, PeRitOneal MalIgnancy Stage Evaluation (PROMISE) internet application (www.e-promise.org) has been developed to facilitate tabulation and automatically calculate surgically validated peritoneal cancer index (PCI), and other surgically validated scores as Gilly score, simplified peritoneal cancer index (SPCI), Fagotti and Fagotti-modified scores. This application offers computer-assistance to produce simple, quick but precise and standardized pre, intra and postoperative reports of the extent of peritoneal metastases and may help specialized and non-specialized institutions in their current practice but also facilitate research and multicentre studies on peritoneal surface malignancies.

Purpose: To evaluate the tolerance of peritonectomy procedures (PP) combined with intraperitoneal chemohyperthermia (IPCH) in patients with peritoneal carcinomatosis (PC), a phase II study was carried out from January 1998 to September 2001. Patients and Methods: Fifty-six patients (35 females, mean age 49.3) were included for PC from colorectal cancer (26 patients), ovarian cancer (seven patients), gastric cancer (six patients), peritoneal mesothelioma (five patients), pseudomyxoma peritonei (seven patients), and miscellaneous reasons (five patients). Surgeries were performed mainly on advanced patients (40 patients stages 3 and 4 and 16 patients stages 2 and 1) and were synchronous in 36 patients. All patients underwent surgical resection of their primary tumor with PP and IPCH (with mitomycin C, cisplatinum, or both) with a closed sterile circuit and inflow temperatures ranging from 46° to 48°C. Three patients were included twice. Results: A macroscopic complete resection was performed in 27 cases. The mortality and morbidity rates were one of 56 and 16 of 56, respectively. The 2-year survival rate was 79.0% for patients with macroscopic complete resection and 44.7% for patients without macroscopic complete resection (P = .001). For the patients included twice, two are alive without evidence of disease, 54 and 47 months after the first procedure. Conclusion: IPCH and PP are able to achieve unexpected long-term survival in patients with bulky PC. However, one must be careful when selecting the patients for such an aggressive treatment, as morbidity rate remains high even for an experienced team.

Background Insufficient volume of the future liver remnant (FLR) is a major cause of unresectability in patients with bilobar colorectal liver metastases (CLM). The objective of this study was to evaluate the safety and efficacy of the novel associating portal embolization and artery ligation (APEAL) technique before extended right hepatectomy during a two-stage procedure for CLM. Methods All patients who had undergone extended right hepatectomy during two-stage surgery for CLM between 2012 and 2014 were identified retrospectively from a prospectively maintained database. In the first stage, right portal vein embolization, partial right hepatic artery ligation and devascularization of segment IVb along the round ligament without parenchymal transection were associated with clearance of the FLR and/or primary tumour resection. Liver volumetry was performed using OsiriX software on postoperative day (POD) 7 and 30. Results Ten patients underwent the APEAL procedure. During the first stage, APEAL was combined with colorectal resection in seven patients. The median (range) interval between the two stages was 45 (31–71) days. The FLR volume increased from 327 (214–537) cm3 before surgery to 590 (508–1072) cm3 on POD 7 and 701 (512–1018) cm3 on POD 30. This corresponded to a FLR regeneration rate of 104 (42–185) and 134 (53–171) per cent respectively. There were no deaths. The overall morbidity rate was 60 per cent (6 of 10) after each procedure, with severe morbidity occurring in two and three of ten patients after the first and second procedures respectively. Conclusion APEAL induces fast, safe, reproducible and effective FLR growth when an extended right hepatectomy is scheduled in patients with multiple bilobar CLM.

Resume But de l’etude : L’exerese carcinologique des tumeurs retroperitoneales necessite parfois l’exerese d’un segment de veine cave inferieure envahi. Le but de cette etude retrospective etait de rechercher si la reconstruction de l’axe cave inferieur etait necessaire, et apportait un avantage. Patients et methodes : Cette etude unicentrique etalee sur 20 ans a porte sur quatre patients ayant eu une resection segmentaire de la veine cave inferieure envahie par une tumeur retroperitoneale, sans reconstruction cave. Il s’agissait d’un cancer du rein, d’un phreochromocytome malin, d’un histofibrome malin et d’un carcinome indifferencie retroperitoneaux. La resection cave a siege dans trois cas au niveau du confluent renal, accompagnee d’une nephrectomie droite et dans un cas au-dessus du confluent renal, au niveau de sa portion retro-hepatique. Resultats : Dans les suites operatoires, il y a eu seulement une insuffisance renale tres passagere dans un cas. Un patient a developpe une thrombose veineuse profonde du membre inferieur droit trois mois apres l’operation et une autre 30 mois apres l’operation. Un patient est decede de recidive cancereuse au 19e mois. Trois patients etaient en vie sous traitement anticoagulant avec 2, 6, et 15 ans de recul, sans sequelle. Conclusion : La reconstruction prothetique actuellement realisable pour remplacer un segment de veine cave expose au risque de thrombose et de sepsis et ne semble justifiee que dans les cas ou la circulation veineuse de suppleance est insuffisante. Dans les cas d’envahissement cave par une tumeur de voisinage, la reduction progressive du flux cave entraine habituellement le developpement d’une circulation veineuse de suppleance, ce qui rend inutile la reconstruction de la veine cave inferieure apres resection partielle.

Resume But de l’etude : Cette etude retrospective avait pour but d’evaluer a partir d’une serie de 350 adenocarcinomes gastriques, l’evolution de leurs caracteristiques et de leur traitement chirurgical entre 1970 et 1996. Patients et methode : De 1970 a 1996, 350 patients ont ete operes pour un cancer gastrique (cancer du cardia exclu) dans le meme centre. L’âge moyen etait de 68,8 ans et le sex-ratio de 1,4. Ces patients ont ete divises en trois groupes qui ont ete analyses et compares (groupe 1 opere de 1970 a 1978, groupe 2 de 1979 a 1987, groupe 3 de 1988 a 1996). Resultats : Le cancer antropylorique est reste le plus frequent (56 % dans le groupe 3). La taille des tumeurs a diminue mais il y avait dans le groupe 3 plus de tumeurs indifferenciees (54,2 %), plus de tumeurs avec envahissement ganglionnaire (72 %). Le nombre de cancers diagnostiques au stade III et IV est reste eleve (70 % dans le groupe 3) et le nombre de cancers superficiels faible (9,9 %). Le traitement chirurgical est devenu plus radical avec augmentation du nombre de gastrectomies totales et curage ganglionnaire plus etendu. Une radiotherapie adjuvante per- et postoperatoire a ete associee a partir de 1985. La mortalite postoperatoire a diminue (13,3 % dans le groupe 1 et 6,1 % dans le groupe 3) (p = 0,04) de meme que la morbidite (31,8 % dans le groupe 1 et 17,5 % dans le groupe 3). La survie actuarielle a cinq ans est passee de 18,9 % dans le groupe 1 a 39,2 % dans le groupe 2 (p = 0,003) ; chez les patients ayant eu une radiotherapie complementaire, elle etait globalement de 59,8 % et chez les patients ayant un envahissement ganglionnaire de 43,6 %. Conclusion : Le pronostic de l’adenocarcinome gastrique reste mauvais. L’evolution vers un traitement chirurgical plus radical n’a pas augmente le taux des complications postoperatoires et a permis l’amelioration du taux de survie. De nouveaux traitements complementaires, dont la radiotherapie adjuvante, doivent etre evalues en vue de poursuivre cette amelioration du pronostic.

Increasing evidence suggests that endothelial cells are involved in tumor growth and metastasis. E-selectin, an adhesion molecule specifically expressed or secreted by activated endothelial cells, may enhance tumor angiogenesis and the adhesion of tumor cells to endothelial cells at distant sites. The aim of this study was to assess the relationship between concentrations of circulating soluble E-selectin and clinical, pathological and biological features in patients with breast cancer (BC). sE-selectin concentrations were analyzed by an ELISA method in sera from 113 patients with metastatic BC, 30 patients with primary inflammatory BC, 105 patients with primary non-inflammatory BC, 456 patients with node-negative BC, and 42 healthy controls. sE-selectin in the metastatic BC group was significantly higher than in the healthy control group. In metastatic BC, sE-selectin was significantly higher in patients with liver metastases than in patients without liver metastases. In patients with primary non-inflammatory BC, a negative correlation was found between sE-selectin concentrations and tumoral microvessel count. In overall and disease-free survival studies performed in the node-negative population (median follow-up duration 7.5 years), multivariate analyses demonstrated a prognostic value of sE-selectin and tumor size. This study suggests that endothelial activation might play a role in the development of BC. This role seems not to be related to angiogenesis.

The BRCA1 gene modification is responsible for an autosomal dominant syndrome of inherited early onset breast and/or ovarian cancer. This gene is estimated to account for almost half of inherited breast cancers and three quarters of inherited breast/ovarian cancers. This suggests that about 1 in every 500 women may carry the BRCA1 mutation. The BRCA1 was isolated by positional cloning in 1994. More than 100 different mutations have been found in the germline of affected individuals. Using systematic sequencing, we looked at BRCA1 germline mutations in 84 patients treated at the Centre Oscar Lambret for breast and/or ovarian cancer who belonged to high-risk families. We found 39 mutations: 22 true mutations inducing modifications of the BRCA1 protein (BRCA1+), six mutations with unknown consequences on the BRCA1 protein, and eleven mutations corresponding to polymorphisms that had been described previously. All the BRCA1+ cases had a HPG3 tumour. The median age of discovery and the receptor positivity percentage are lower in hereditary breast cancer than in the standard population of the breast cancers treated in our centre. Conversely, most of the BRCA1+ patients are without node involvement. This shows that BRCA1 mutations are not always related to parameters thought to indicate a bad prognosis.

Aims : High local failure rates in gastric cancer have been reported, up to 67%. To achieve a better local control, we evaluated intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT) in association with surgery for gastric cancer patients with lymph node involvement. We report here the analysis of the patterns of failure for patients involved in this IORT protocol. Material and methods : Forty-two positive lymph node (N+) gastric cancer patients were operated on (31 total, three subtotal and eight extended gastrectomies) with IORT procedure between 1985 and 1997 (33 males, nine females, mean age 61.3 years). IORT was focused on coeliac area (mean dose 15 Gy), followed by EBRT (46 Gy) in 36 patients. Ten patients were pN1 and 32 were pN2. A concurrent systemic chemotherapy (five Fluoro-Uracil and Cisplatinum) was performed in 14 patients. Results : One patient died postoperatively. Actuarial pN+ 10 year survival rate was 44.8%. The 5 year actuarial local control and disease-free survival rates were 78.8 and 47.5%, respectively. As far as patterns of failure were explored, 5 patients have a local coeliac recurrence (12%) and 12 have distant metastases with no evidence of coeliac recurrence. Conclusion : This retrospective analysis suggests a potential effect of IORT and/or EBRT in promoting local control and long-term survival in gastric cancer patients with lymph node involvement.

PURPOSE: The majority of colorectal carcinomas diagnosed are adenocarcinomas. Squamous-cell carcinoma is a rare pathologic curiosity. Since 1943, only 18 cases have been described in the medical literature. The aim of this study was to report retrospectively six new cases and to review the medical literature. PATIENTS: Of the 6 cases, 4 were females, and age ranged from 43 to 93 years. Tumors were located 7 to 12 (mean, 8.5) cm from the anal verge. Five patients underwent surgical resection. Intraoperative radiotherapy was performed in one case. One patient was treated only by external beam radiotherapy. In two cases neoadjuvant combination of external beam radiotherapy and chemotherapy and in one case neoadjuvant contact x-ray treatment were performed. This treatment was followed by external beam radiotherapy in two cases and by chemotherapy in two cases, in patients with lymph node involvement. RESULTS: The clinical tumor response to radiotherapy was almost complete for the patient who did not undergo surgery. One tumor was sterilized by preoperative radiation. Three patients were alive without recurrence at 6 months, 2 years, and 16 years. CONCLUSION: The etiopathogenicity of squamous-cell carcinoma of the rectum is discussed. The prognosis of these tumors seems to be worse than that for adenocarcinoma because of a delayed diagnosis. Surgical resection seems to be the most important treatment. Chemotherapy and especially radiotherapy may have some indications.

BACKGROUND: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAI-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). METHODS: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. RESULTS: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph node-negative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P

Nerve growth factor (NGF) has been shown recently to be mitogenic for human breast cancer cells. In the present study, we have assayed the expression of NGF receptors (NGFRs: TrkA and p75) mRNAs in 363 human primary breast cancers, using real-time quantitative reverse transcription-PCR. NGFRs were found in all of the tumor biopsies. TrkA and p75 were positively correlated and were respectively associated with the histoprognostic grading and the tumor type. NGFRs were both related to progesterone receptors. In univariate analyses, TrkA (upper quartile) was associated with longer overall survival. Histoprognostic grading, tumor size, node involvement, and steroid receptors were also prognostic factors. In Cox multivariate analyses, TrkA was not a prognostic parameter. This study demonstrates the expression of NGFRs in breast cancer and points out that patients with high levels of TrkA have a more favorable overall survival prognosis.

We performed a competitive binding study with 125I-labelled FGF (fibroblast growth factor)-2 and unlabelled FGF-2 in an unselected series of two hundred and thirty human primary breast cancers. One hundred and ninety-two breast cancer biopsies possessed FGF-2 low-affinity binding sites (FGF-2 LABS). The median dissociation constant was 2.4 nM (range, 1.03-18) and the median concentration of membrane protein was 6187.5 fmol/mg (range, 831-90,000). FGF-2 LABS concentrations were positively correlated to the progesterone receptor level. Cox univariate analyses showed that the FGF-2 LABS (or = upper quartile) was associated to a longer overall survival (p = 0.05; RR = 0.042); node involvement, estrogen receptor progesterone receptor and histoprognostic grading were also prognostic. In Cox multivariate analyses, only the progesterone receptor, estrogen receptor, node involvement and FGF-2 LABS were prognostic factors; the FGF-2 LABS were associated with a longer overall survival (p = 0.033; RR = 0.068). The present study showed that FGF-2 LABS have only a limited role as a prognostic factor in breast cancer.

The class of molecular chaperones known as 14-3-3 is involved in the control of cellular growth by virtue of its apparent regulation of various signaling pathways, including the Raf/mitogen-activated protein kinase pathway. In breast cancer cells, the sigma form of 14-3-3 has been shown to interact with cyclin-dependent kinases and to control the rate of entry into mitosis. To test for a direct role for 14-3-3 in breast epithelial cell neoplasia, we have quantitated 14-3-3 protein levels using a proteomic approach based on two-dimensional electrophoresis and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF). We show here that 14-3-3sigma protein is strongly down-regulated in the prototypic breast cancer cell lines MCF-7 and MDA-MB-231 and in primary breast carcinomas as compared with normal breast epithelial cells. In contrast, levels of the alpha, beta, delta, or zeta isoforms of 14-3-3 were the same in both normal and transformed cells. The data support the idea that 14-3-3sigma is involved in the neoplastic transition of breast epithelial cells by virtue of its role as a tumor suppressor; as such, it may constitute a robust marker with clinical efficacy for this pathology.

Objectifs Determiner la valeur pronostique et la valeur predictive pour l’apparition d’une carcinose peritoneale de la cytologie peritoneale dans les adenocarcinomes colorectaux et gastriques. Materiels et Methodes De 2001 a 2007, 1300 patients presentant un cancer d’origine digestive ont ete inclus dans le protocole EVOCAP 2, etude prospective multicentrique (19 centres). Une cytologie peritoneale etait realisee au debut de chaque intervention. La survie globale, la survie sans recidive a deux ans et la survenu d’une carcinose peritoneale ont ete analysees en fonction des resultats de la cytologie. Resultats Les resultats intermediaires sur 367 patients etaient les suivants : la presence de cellules malignes detectee par la cytologie peritoneale est un facteur pronostique pejoratif en termes de survie globale pour les cancers coliques (Hazard ratio = 13,3, p = 0,0018) et en termes de survie sans recidive pour les cancers gastriques (hazard ratio = 8,49, p = 0,0376). L’incidence des cytologies positives est correlee significativement avec le stade pTNM, la presence d’ascite ou de carcinose peritoneale et la realisation d’un traitement neo-adjuvant. Le controle des dernieres cytologies est actuellement en cours, et l’analyse statistique sera realisee en mai ce qui permettra de presenter en octobre les resultats definitifs sur la serie globale de 1300 patients. Conclusion La cytologie peritoneale est un facteur pronostique pejoratif pour les adenocarcinomes coliques et gastriques. La survie globale des patients presentant des cellules malignes sur une cytologie peritoneale est equivalente a ceux presentant un cancer de stade IV. Les resultats definitifs sur la serie de 1300 patients permettront d’evaluer le caractere predictif de la cytologie peritoneale sur la survenue d’une carcinose peritoneale.

We measured the expression of the type I growth factor receptor gene family [epidermal growth factor receptor (EGFR), c-erbB-2, c-erbB-3 and c-erbB-4] in a series of 365 unselected primary breast cancers. The expression was quantified with a real-time one-step reverse transcriptase-PCR (RT-PCR) assay, based upon the 5' nuclease activity of the Taq polymerase and using an Abi Prism 7700 Sequence Detector System (Perkin-Elmer, Courtaboeuf, France). c-erbB-3 and c-erbB-4 were positively correlated to each other (Spearman test) and negatively correlated to EGFR. EGFR and c-erbB-2 were inversely correlated to the presence of estradiol receptors (ER) and progesterone receptors (PgR), and positively correlated to the histoprognostic grading (HPG). Conversely, c-erbB-3 and c-erbB-4 were positively correlated to the presence of ER and PgR, and inversely correlated to the grading HPG. EGFR was inversely related (chi2 test) to the presence of ER and PgR, and positively associated with HPG. In contrast, both c-erbB-3 and c-erbB-4 were inversely related to HPG, and positively associated with the presence of ER and PgR. The expression level of EGFR and c-erbB-2 was significantly higher in ER- and PgR-negative tumors compared with ER- and PgR-positive tumors (Student's t test), and in tumors with higher grade compared with tumors with lower grade. The expression level of c-erbB-3 and c-erbB-4 was significantly higher in ER- and PgR-positive tumors compared with ER- and PgR-negative tumors and in tumors with lower grade compared with tumors with higher grade. In overall survival studies, Cox univariate analyses showed prognostic values of EGFR [or = median; P = 0.026; risk ratio (RR), 1.6], c-erbB-3 (or = median; P = 0.0093; RR, 0.58), c-erbB-4 (or = median; P = 0.0024; RR, 0.52), HPG, node involvement, tumor diameter, ER, and PgR. In Cox multivariate analyses, tumor diameter, ER, and PgR had a prognostic value. In relapse-free survival studies, univariate analyses demonstrated prognostic values of tumor diameter, node involvement, and c-erbB-4 (P = 0.015; RR, 0.65). These three parameters maintained their prognostic value in multivariate analyses (c-erbB-4, P = 0.035; RR, 0.67). This study confirms that EGFR expression and c-erbB-2 expression are markers of tumor aggressiveness in breast cancer. Conversely, we demonstrate that c-erbB-3 and c-erbB-4 elevated expressions are associated with a better prognosis.

We developed a real-time one-step reverse transcriptase-polymerase chain reaction (RT-PCR) method for the routine quantification of c-erbB-2 oncogene expression in breast cancer, using a 7700 ABI PRISM Sequence Detector System (Perkin Elmer-Applied Biosystems, Courtaboeuf, France). The real-time quantification of the polymerase chain reaction products is based on the TaqMan 5' nuclease assay. The optimal experimental conditions we determined were as follows: 6 mM MgCl2, 200 nM of fluorogenic probe, 200 nM of each primer, and 12.5 units MuLV reverse transcriptase. The GAPDH housekeeping gene was used for normalization of c-erbB-2 expression. In human breast cancer cell lines, the normalized expression of c-erbB-2 ranged from 8 x 10(-6) to 2,600 x 10(-6), the two highest values corresponding to the c-erbB-2 overexpressing cells MDA-MB-453 and SK-BR-3. In a series of 100 breast cancer samples, c-erbB-2 normalized expression was found to range from 0.4 x 10(-6) to 350 x 10(-6). A close correlation was observed between this real-time one-step quantitative RT-PCR method and both semiquantitative conventional RT-PCR (N = 22; r = 0.8543; P.0001) and c-erbB-2 protein expression (p185) quantified by an enzyme immunoassay (EIA) (N = 27; r = 0.71; P.0001). The current realtime RT-PCR assay is rapid, sensitive, and reproducible and appears particularly suitable to quantify gene expression in large series of samples.

Endostatin is an angiogenesis inhibitor derived from type XVIII collagen. The aim of this study was to determine the concentrations of circulating endostatin in patients with systemic sclerosis (SSc), and to assess the relationship between these concentrations, extension of tissular sclerosis, and presence of cutaneous scars or ulcers.The study involved 50 patients with SSc and 30 healthy subjects. Cutaneous extension of sclerosis was graded according to Barnett's classification system: 33 patients had grade I SSc and 17 patients had grades II or III SSc. The results of pulmonary function tests were abnormal in 31 of 50 patients, 8 of whom also had abnormalities on chest radiograms. Cutaneous scars or ulcers were found in 22 of 50 patients. Endostatin concentrations were determined using a competitive enzyme immunoassay method.The mean circulating endostatin concentration was significantly higher in the SSc group than in the healthy subjects group (mean +/- SD 53.2 +/- 22.4 ng/ml versus 9.9 +/- 9.7 ng/ml; P10(-4)), in patients with grade II or grade III SSc than in patients with grade I SSc (63.2 +/- 20.2 ng/ml versus 45.1 +/- 15.6 ng/ml; P10(-2)), in patients with abnormal findings on chest radiograms than in patients with normal findings on chest radiograms (67.6 +/- 22.4 ng/ml versus 50.4 +/- 21.6 ng/ml; P0.05), and in patients with cutaneous scars or ulcers than in patients without these manifestations (60.9 +/- 25.9 ng/ml versus 47.2 +/- 13.3 ng/ml; P10(-2)).Circulating endostatin concentrations are significantly increased in patients with SSc. Production of endostatin may result from tissular sclerosis and could contribute to the development of ischemic manifestations.

E-cadherin is a prominent factor in maintaining the epithelial architecture, and loss of its normal function is considered to be a key element in cancer invasion. In breast cancer, correlation between alteration of E-cadherin expression and histological type has been reported, but associations with other parameters remain uncertain. To refine these findings and to explore the biological significance of features thought to result from alterations of cell-to-cell adhesion systems, rare in sporadic cases but more frequent in BRCA1-associated breast cancers (BRCA1-BCs), we investigated E-cadherin expression by immuno-histochemistry in a combined panel of 214 breast cancers enriched in hereditary cases (176 sporadic cases and 38 BRCA1-BCs). Following multivariate statistical analysis using a logistic regression model, only 2 parameters were significantly associated with loss of E-cadherin expression: lobular histological type (p0.0001), in agreement with previous results, and syncytial growth pattern (SGP) (p = 0.01). The latter result provides a biological basis for SGP, the cardinal feature of medullary breast carcinoma.

Several studies have suggested that endothelial cells participate in tumor development. Soluble E-selectin (sE-selectin) is specifically released by activated endothelial cells, and its serum concentration can be considered a marker of endothelial activation. In this study, we assessed the prognostic value of sE-selectin concentrations in node-negative breast cancer patients. Serum sE-selectin concentrations were measured by an ELISA method prior to surgery in 456 node-negative breast cancer patients. We analyzed also tumor size (TS), histoprognostic grading, and steroid hormone receptor status. The mean sE-selectin concentration was 24.9 +/- 15.0 ng/ml. The sE-selectin concentrations were mildly correlated with the TS but not with the other factors. For prognostic analyses, the median follow-up duration was 7.5 years. The cutoff sE-selectin concentration used was 40 ng/ml. In overall survival studies, univariate analyses demonstrated a prognostic value of sE-selectin, TS, and histoprognostic grading, and multivariate analyses demonstrated a prognostic value of sE-selectin and TS. For disease-free survival, univariate and multivariate analyses demonstrated a prognostic value of sE-selectin and TS. sE-selectin concentration is an easily measurable and strong prognostic factor in node-negative breast cancer patients. These results provide further evidence for the role of adhesion molecules expression by endothelial cells in tumor progression.

Since there is a lack of common family profile among BRCA1-gene carriers, and since the risk of being a mutation carrier is not limited to women with a family history of breast or ovarian cancer, multivariate statistical analysis using the logistic-regression model was carried out, to discriminate between sporadic cases and BRCA1-breast cancers (BRCA1-BCs), especially when information about the family history of breast/ovarian cancer and ethnicity are irrelevant or unavailable, in order to offer specific medical treatment to this population. We examined 32 BRCA1-BCs selected at cancer genetic clinics and 200 consecutive controls without family history of breast cancer for age at onset and current morphological parameters. Following the multivariate analysis, 3 parameters only, namely, early age at cancer onset [odds ratio (OR) for each year = 1.16; p0.0001], estrogen-receptor negativity (OR = 5.7; p = 0.01) and poor differentiation (OR = 5; p = 0.03) were found significant factors for predicting BRCA1-carrier status. The expected impact in BRCA1 screening of our model was estimated using data on 5700 breast-cancer cases from a hospital-based registry. Only 50 and 15% of tumours with early age at onset below 35 years present one or the other 2 discriminant parameters respectively. Consequently, whereas the probability of finding a BRCA1 mutation is rated low (6.2%) when the sole criterion of early onset up to the age of 35 years is used, based on our model, in the sub-group of women with a tumor that is both estrogen-receptor-negative and poorly differentiated the mutation-detection rate is predicted to be above the 10% chance level recommended by the ASCO guidelines. This sub-group of women, representing about 1% of all breast-cancer cases in Western countries, consequently deserves to be tested.

We performed a saturation binding study with 125I-labeled FGF (fibroblast growth factor)-2 in a nonselected series of 250 human primary breast cancers. Two hundred twenty-five breast cancer biopsies possessed bFGFR (basic FGF receptor). The median dissociation constant was 0.35 nM (range, 0.014-1.9), and the median concentration was 1126 fmol/mg protein (range, 49-7328). FGFR-1 was localized, using a specific monoclonal antibody, in cancerous cells and in epithelial cells in normal breast or in benign tumors. In all of the tissues studied, light stromal cell staining was also observed. Thus, the localization of FGFR-1 in carcinoma cells supports the hypothesis that an important part of FGF-2 binding reflects binding to FGFR-1. bFGFR concentrations were positively correlated to estrogen receptor and progesterone receptor levels. Cox univariate analyses showed that the bFGFR (or = upper quartile) was associated to longer relapse-free survival [P = 0.004; RR (risk ratio), 0.46] and overall survival (P = 0.001; RR, 0.35); age, estrogen receptor levels, progesterone receptor levels, node involvement, tumor diameter, and histoprognostic grading were prognostic, also. In Cox multivariate analyses, only the bFGFR, age, node involvement, and histoprognostic grading were prognostic factors; the bFGFR was associated with longer relapse-free survival (P = 0.03; RR, 0.4) and overall survival (P = 0.009; RR, 0.3). The present study confirms that FGF could be an important regulator of human breast cancer growth and that patients with a high level of bFGFR had a better prognosis.

Increasing evidence suggests that E-selectin contributes to tumor growth and metastasis. E-selectin may increase tumoral angiogenesis and the adhesion of tumoral cells to endothelial cells at distant sites. The aim of this study was to assess the relationship between concentrations of circulating soluble E-selectin (sE-selectin) and clinical, pathological, and biological features in patients with breast cancer (BC). Concentrations of sE-selectin were analyzed by an ELISA method in sera from 113 patients with metastatic BC, 30 patients with primary inflammatory BC, 105 patients with primary noninflammatory BC, and 42 healthy controls. These concentrations were analyzed in terms of the clinical and pathological features of the tumors as well as in terms of the concentrations of serum inflammatory parameters (erythrocyte sedimentation rate, C reactive protein, interleukin 1 beta, and tumor necrosis factor alpha), the response to chemotherapy or hormone therapy, and the survival duration. Tumoral angiogenesis was also assessed in 68 patients with primary noninflammatory BC who had had primary surgery. The mean concentration of sE-selectin in the metastatic BC group was significantly higher than the mean concentration found in the healthy control group (33.5 versus 21.8 ng/ml; P0.01). In metastatic BC, the mean concentration of sE-selectin was significantly higher in patients with liver metastasis than in patients without liver metastasis (55.3 versus 26.0 ng/ml; P10(-5). The univariate analysis showed that high concentrations of sE-selectin were associated with reduced overall survival (P0.05), but this probably reflected the association between high concentrations of sE-selectin and liver metastasis. In patients with primary noninflammatory BC, a negative correlation was found between sE-selectin concentrations and the tumoral microvessel count (r = -0.47; P = 10(-4). In patients with primary inflammatory or noninflammatory BC, no correlation was found between concentrations of sE-selectin and tumor size, lymph node involvement, response to chemotherapy or hormone therapy, and survival. No correlation was found between the concentrations of sE-selectin and serum inflammatory parameters in any of the patient groups. This study suggests that in patients with metastatic BC, levels of sE-selectin are higher in the presence of liver metastasis. In patients with primary BC, high concentrations seem to be associated with reduced tumoral angiogenesis. Although several studies have previously demonstrated that the expression of cell surface E-selectin enhances the metastatic process, the shedding of sE-selectin in circulation may be considered a mechanism of inhibition of tumor progression.

In the present study, we have investigated specific growth hormone (GH) receptor gene expression in breast cancer cell lines and tissues. By Northern blot analysis, using a human GH receptor cDNA probe, the classically observed 4.7-kilobase GH receptor mRNA was evidenced in 2 of 29 cancer biopsies and in the MCF7 and T47-D cell lines. Reverse transcription coupled to PCR was used to amplify the GH receptor sequence encompassing a part of the extracellular domain as well as the transmembrane domain. An amplification product of the expected size (456 base pairs) was observed in 28 of 29 breast biopsies and in all the breast cancer cell lines studied (T47-D, MCF7, MDA-MB-231, and BT-20). The reverse transcription-PCR product was shown to be specific by Southern blot hybridization with the GH receptor cDNA probe and by specific cleavage of the amplified products with restriction enzymes. For the first time, the expression of GH receptor gene in breast cancer cell lines and biopsies is demonstrated in this study, suggesting a GH-specific action in tumor development. Additionally, the two isoforms of the human GH receptor (hGHR) mRNA, one containing exon 3 (hGHR-wt mRNA) and one excluding exon 3 (hGHR-d3 mRNA), were found to be expressed independently or simultaneously (29 tumors analyzed). The presence of hGHR-d3 mRNA appears to be patient specific, as demonstrated by comparing the expression pattern of both mRNAs between tumor biopsy and lymphocytes of the same patient.

p53 antibodies have been found in sera of patients with breast and lung carcinomas and in children with B-lymphomas. We report here the presence of p53 antibodies in sera of patients with 11 different types of cancer. The frequency of seropositives for p53 varied among the different types of cancer, but a correlation with the frequency of p53 gene alteration was established. Using a powerful peptide enzyme-linked immunosorbent assay, we demonstrated that the immune response of patients with p53 antibodies was restricted to a small subset of peptides localized in the amino and carboxy termini of p53, whatever the type of cancer. Given the similarities of the patterns of immune responses in patients with p53 antibodies and animals hyperimmunized with human p53, we propose that the p53 humoral response is the result of a self-immunization process which is itself the consequence of p53 protein accumulation in tumor cells.

Abstract #3012 Background: Sentinel lymph node (SLN) status is highly predictive of overall axillary lymph node involvement. SLN positive patients(pts)with macro or micrometastasis require delayed axillary clearance. Intraoperative imprints have a good sensitivity for detection of macrometastasis but micrometastases are seldom diagnosed. Thus, we tested the intraoperative determination of axillary node metastasis according to the Rapid Gene Search Breast Lymph Node (BLN) Assay (Veridex) based on RT-PCR. Patients and methods:50 pts operated between September 17 and March 20 ,2008, had a SLN procedure. Lymph nodes were cut in 2 mm slices, and 1 out of 2 was examined with Rapid BLN Assay; the other one had intraoperative imprints and definitive histological assessement in paraffin-embedded sections including serial slices with hematoxilin eosine safran coloration and Cytokeratine AE1-AE3 immunochemistry. Results : 103 lymph nodes were examined with a median number of 2 SLN by pt. With Rapid BLN Assay, 12(9 pts) were positive and confirmed by histological interpretation on the other half for 11 (8 pts). 89 lymph nodes were negative (41 pts); in 1 (1 pt), isolated tumor cells (CTI) were detected in the other half at histological interpretation. Intraoperative imprints detected 4 macrometastases. One node declared positive at the intra-operative examination imprint corresponded to a granulomatous lesion after histological interpretation and Rapid BLN Assay was negative. Sensitivity was 31% for intraoperative imprints, 92% for Rapid BLN Assay and the histological examination of paraffin--embedded sections. The median time for intraoperative determination was 34 minutes for 1 SLN compared with 20 minutes for imprints. Conclusion: Given the high sensitivity of the rapid BLN assay, the excess duration of the procedure is acceptable for the surgeon. Furthermore, this procedure avoids a secondary axillary clearance in pts without intraoperative examination or with negative imprints and with metastases in SLN. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3012.

Overall survival (OS) and relapse free survival (RFS) were studied in 297 patients according to the presence of insulin-like growth factor 1 receptors (IGF1-R). All the patients were surgically treated for locoregional disease in the same institution from January 1986. The median duration of follow-up was 40 months. RFS was better in patients with IGF1-R in their tumors as assessed by actuarial survival (P = 0.014) as well as Cox analysis (P = 0.016). OS was better in IGF1-R positive tumors studied by actuarial (P = 0.007) as well as Cox analysis (P = 0.010). By Cox analysis the other prognostic factors on RFS were estrogen receptor (P = 0.002), progesterone receptor (P = 0.002), axillary node metastases (P = 0.032), histoprognostic grading (GHP) according to the standard of Scarff and Bloom (P = 0.004), and tumor diameter (P = 0.019). The other prognostic factors on OS (Cox analysis) were estrogen receptor (P = 0.001), axillary node metastases (P = 0.010), GHP (P = 0.009), progesterone receptor (P = 0.012), and tumor diameter (P = 0.007). When combining IGF1-R, GHP, and axillary node metastases, it appeared that IGF1-R, GHP, and axillary node metastases had independent prognostic significance. In this prospective study IGF1-R had a prognostic significance on RFS as well as on OS studied by actuarial as well as Cox analysis.

A continuous line of human breast carcinoma cells, VHB-1, was established in culture following collagenase treatment of an infiltrating duct cell carcinoma. The cells displayed an epithelial pattern and multiplied rapidly. Maintained in monolayer culture, the VHB-1 cells exhibited a 30-h doubling time and a plating efficiency of 20%. The cells possessed an abnormal karyotype with a mode of 70-74 chromosomes per cell. The karyotype was heavily rearranged and numerous marker chromosomes were found. Transplantation of the cells into nude mice produced tumors bearing histological resemblance to the original material. The VHB-1 cells contained significant levels of prolactin receptors, were steroid hormone (estrogen, progesterone, androgen, glucocorticoid) receptor positive, and were capable of functional differentiation in vitro. These characteristics make the VHB-1 cell line a suitable model for studying the biological properties of human breast tumors.