Association between post-operative hPG80 (circulating progastrin) detectable level and worse prognosis in glioblastoma.

BACKGROUND: Patients with glioblastomas have a dismal prognosis, and there is no circulating predictive or prognostic biomarker. Circulating progastrin, hPG80, is a tumor-promoting peptide present in the blood of patients with various cancers that has been shown to have prognostic value. We evaluated the prognostic value of plasma hPG80 in patients with isocitrate dehydrogenase-wild type glioblastoma after surgery. PATIENTS AND METHODS: A multicentric retrospective study in glioblastoma patients treated with standard radio-chemotherapy was conducted. The hPG80 levels were measured in plasma EDTA samples collected after surgery with an ELISA DxPG80.lab kit (Biodena Care, Montpellier, France), which has a detection threshold of 1.2 pM. The relationship between post-operative hPG80 plasma levels, in combination with other known prognostic factors, and patients' progression-free survival (PFS) and overall survival (OS) was evaluated. RESULTS: Sixty-nine patients were assessable. Plasma samples were collected after tumor biopsy (B), partial resection (PR), and complete resection (CR) for 22, 25, and 22 patients, respectively. At a median concentration of 5.37 pM (interquartile range 0.00-13.90 pM), hPG80 was detected in 48 (70%) patients (hPG80+). CR was associated with significant lower values of hPG80 levels: the median value was 0.7 versus 9.1 pM for PR (P = 0.02) and 8.3 pM for B (P = 0.004). The hPG80 detection rate was also significantly lower: 50% (CR) versus 72% (PR) versus 86% (B) (P = 0.005). The median follow-up was 39 months [22.4 months-not reached]. hPG80 post-operative detection was associated with numerically shorter PFS (6.4 versus 9.4 months, P = 0.13) and OS (14.5 versus 20.9 months, P = 0.11). In multivariate analysis, hPG80 was a prognostic factor for OS (P = 0.034). CONCLUSIONS: Circulating hPG80 could serve as a new prognostic biomarker after surgery in patients with glioblastoma treated with radio-chemotherapy.

[Magnetic Resonance Imaging for local preoperative staging in endometrial cancer: Nantes local experience]. / Performances de l'IRM dans le bilan d'extension locale préopératoire des cancers de l'endomètre : l'expérience nantaise.

OBJECTIVES: To determine the diagnostic accuracy of magnetic resonance imaging (MRI) for local preoperative staging in endometrial cancer in our center (Centre Hospitalier Universitaire de Nantes: CHU), since the French National Cancer Institute's surgery recommendations publication in 2010, especially for the prediction of myometrial and cervical stromal invasion. METHODS: Retrospective monocentric study of consecutive women operated of endometrial cancer in gynecology department of CHU de Nantes, who underwent preoperative pelvic MRI in our Radiology department from November 2010 to November 2016. MRI data collected from initial report and compared to surgical histological findings as gold standard. RESULTS: Sixty-four patients were included. Deep myometrial invasion was present in 35 patients in MRI versus 34 patients on postoperative histology (5 false positives, 4 false negatives). Cervical stromal invasion was present in 9 patients in MRI versus 19 patients on postoperative histology (2 false positives, 12 false negatives). The sensitivity and the specificity were respectively 88.23% (95% confidence intervals (CI) [0.71-0.96]) and 83.33% (CI [0.64-0.93]) for the deep myometrial invasion; 36.84% (CI [0.17-0.61]) and 95.55% (CI [0.83-0.99]) for the cervical stromal invasion. CONCLUSION: Our results were comparable to the literature data, with a low sensitivity for the cervical stromal invasion detection, driving us to change our MRI protocol with optional high-resolution T2 sequences perpendicular to the cervical canal if necessary.

Interactions between cancer-associated fibroblasts and tumor cells promote MCL-1 dependency in estrogen receptor-positive breast cancers.

Selective inhibition of BCL-2 is expected to enhance therapeutic vulnerability in luminal estrogen receptor-positive breast cancers. We show here that the BCL-2 dependency of luminal tumor cells is nevertheless mitigated by breast cancer-associated fibroblasts (bCAFs) in a manner that defines MCL-1 as another critical therapeutic target. bCAFs favor MCL-1 expression and apoptotic resistance in luminal cancer cells in a IL-6 dependent manner while their own, robust, survival also relies on MCL-1. Studies based on ex vivo cultures of human luminal breast cancer tissues further argue that the contribution of stroma-derived signals to MCL-1 expression shapes BCL-2 dependency. Thus, MCL-1 inhibitors are beneficial for targeted apoptosis of breast tumor ecosystems, even in a subtype where MCL-1 dependency is not intrinsically driven by oncogenic pathways.

Masson's tumor revealed by an intracerebral hematoma. Case report and a review of the literature.

We report the case of a 56-year-old woman who underwent total resection of a Masson's tumor or intravascular papillary endothelial hyperplasia (IPEH), which was discovered due to a left temporal intracerebral hematoma revealed by aphasia. IPEH is more often localized on cutaneous and subcutaneous locations, intracranial IPEH are rare and only approximately twenty cases have been published to date. These tumors are a benign vascular lesion composed of papillary intravascular proliferation of epithelial cellular associated thrombosis with fibrin deposits responsible for vascular lumen obliteration. Differential diagnoses of neurological locations of IPEH are more often an angiosarcoma, or meningioma, and metastasis. Magnetic Resonance imaging (MRI) and CT-scan are not specific. On CT-scan the lesion is hypodense without calcification with a peripheral enhancement and on MRI a hyposignal T1 with homogeneous enhancement and a hypersignal T2. Arteriography may reveal a tumoral blush and arterio-venous shunt or arterial pedicles which can be embolized. The age of discovery is between 12 and 70 with a female predominance. IPEH are often localized close to the venous sinus or can be developed in a vascular malformation, thrombus or aneurysm. The curative treatment is total resection but recurrence has been reported, long-term follow-up with MRI is recommended.

Prognostic and therapeutic factors of gliosarcoma from a multi-institutional series.

The aims of this multicentre retrospective study were to identify prognostic or therapeutic factors impacting on overall survival in patients with gliosarcoma. The analysis included all patients treated for gliosarcoma between 1998 and 2014 in seven French academic centres. Seventy-five patients with a median age of 60 years (range from 23 to 79 years) were treated with a combination of surgery (n = 66), radiotherapy (adjuvant for 64 patients and exclusive for 8 patients) and temozolomide based chemotherapy (n = 58). Median follow-up was 12 months (range from 2 to 71 months). Two-year overall survival (OS) and disease free survival rates were 12 % (95 % CI 4-20 %) and 2 % (95 % CI 0-6 %), respectively. The median OS was 13 months. Treatment at recurrence consisted of chemotherapy (n = 38) (bevazicumab for 18 patients, repeat temozolomide for 10 patients), salvage surgery (n = 8) and radiochemotherapy (n = 1). In univariate analysis, younger age, higher total dose of radiotherapy, longer time to recurrence and treatment at recurrence significantly increased OS. In multivariate analysis, high total dose of radiotherapy (HR = 0.97, p = 0.007) and treatment at recurrence (HR = 0.28, p < 0.001) were favourable prognostic factors of OS. Radiotherapy at a minimum dose of 54 Gy and salvage treatment increased OS of gliosarcoma. Unlike glioblastoma, in our analysis, TMZ based chemotherapy was not associated with an improvement in OS compared to patients who received radiation therapy only.

Chitinase 3-like proteins as diagnostic and prognostic biomarkers of multiple sclerosis.

BACKGROUND: Despite sensitivity of MRI to diagnose multiple sclerosis (MS), prognostic biomarkers are still needed for optimized treatment. OBJECTIVE: The objective of this paper is to identify cerebrospinal fluid (CSF) diagnostic biomarkers of MS using quantitative proteomics and to analyze their expression at different disease stages. METHODS: We conducted differential analysis of the CSF proteome from control and relapsing-remitting MS (RRMS) patients followed by verification by ELISA of candidate biomarkers in CSF and serum in control, clinically isolated syndrome (CIS), RRMS and progressive MS (PMS) patients. RESULTS: Twenty-two of the 527 quantified proteins exhibited different abundances in control and RRMS CSF. These include chitinase 3-like protein 1 (CHI3L1) and 2 (CHI3L2), which showed a strong expression in brain of MS patients, especially in astrocytes and microglial cells from white matter plaques. CSF and serum CHI3L1 levels increased with the disease stage and CIS patients with high CSF (>189 ng/ml) and serum (>33 ng/ml) CHI3L1 converted more rapidly to RRMS (log rank test, p < 0.05 and p < 0.001, respectively). In contrast, CSF CHI3L2 levels were lower in PMS than in RRMS patients. Accordingly, CSF CHI3L1/CHI3L2 ratio accurately discriminated PMS from RRMS. CONCLUSIONS: CSF CHI3L1 and CHI3L2 and serum CHI3L1 might help to define MS disease stage and have a prognostic value in CIS.

Combining two biomarkers, IDH1/2 mutations and 1p/19q codeletion, to stratify anaplastic oligodendroglioma in three groups: a single-center experience.

IDH1/2 mutations and 1p/19q codeletion occur frequently in anaplastic gliomas and are prognostic factors. We combined these two biomarkers to stratify patients treated for anaplastic oligodendroglioma (AO). 43 consecutive WHO AO were selected. We combined immunohistochemistry (IHC) with the monoclonal antibody mIDH1R132H and DNA sequencing of IDH1 and IDH2 genes. Fluorescence in situ hybridization was carried out to evaluate 1p/19q codeletion. These biomarkers were correlated with progression-free survival (PFS) and overall survival (OS). IDH1/IDH2 mutations occurred in 23/43 (54 %) patients: 20/43 IDH1-R132H mutation in IHC, 2/43 IDH1-R132G mutation and 1/43 IDH2-R172K mutation identified by DNA sequencing. 1p/19q codeletion was detected for 23/43 patients. With median follow-up of 19 months (range 1.4-128), median PFS and OS were 22 and 35 months respectively. IDH1/IDH2 mutations were strongly associated with improved PFS and OS: 5-year PFS was 86 versus 6 % and 5-year OS was 91 versus 9 % for patients with IDH1/IDH2 mutations versus wild-type IDH respectively. In multivariate analyses, IDH1/IDH2 mutations and 1p/19q loss were independent prognostic factors. Three groups with distinct prognostic features were identified: patients with IDH1/2 mutations and 1p/19q loss (median PFS, median OS not reached), patients with IDH1/2 mutations or 1p/19q loss (median PFS: 22 months, median OS: 30 months), and patients without IDH1/2 mutations nor 1p/19q loss with a bad prognosis (median PFS: 8.6 months, median OS: 9.9 months). Combining two biomarkers, IDH1/2 and 1p/19q codeletion, makes it possible to stratify AO in three groups with very distinct prognostic features.

Prognostic impact of the expression/phosphorylation of the BH3-only proteins of the BCL-2 family in glioblastoma multiforme.

Apoptosis has a crucial role in anti-cancer treatment. The proteins of the BCL-2 family are core members of the apoptotic program. Thus, we postulated that alterations in the expression of BCL-2 protein family, and in particular in that of the Bcl-2 homology domain 3 (BH3)-only proteins (which can neutralized anti-apoptotic proteins or activate pro-apoptotic proteins) could account for differences in the overall survival (OS) of patients. To test this hypothesis, we analyzed the expression of 15 members of the BCL-2 protein family (Bax, Bak, Bok, Bcl-2, Bcl-xl, Bcl-w, Mcl-1, Bad, Bid, Bim, Bik, Bmf, Hrk, Noxa and Puma) in glioblastoma multiforme (GBM) tumors, the most frequent brain tumor in adults. We found that none of the individual expression of these proteins is associated with a significant variation in OS of the patients. However, when all BH3 proteins were pooled to determine a BH3(score), this score was significantly correlated with OS of GBM patients. We also noted that patients with a have high level of phospho-Bad and phospho-Bim displayed a lower OS. Thus, BH3 scoring/profiling could be used as an independent prognostic factor in GBM when globally analyzed.

Prognostic factors for patients treated for a recurrent FIGO stage III ovarian cancer: a retrospective study of 108 cases.

AIMS: To determine overall survival of patients treated for a first relapse of FIGO stage III ovarian cancer, outside of randomized trial, with a long term follow-up and to identify prognostic factors. MATERIALS AND METHODS: A consecutive series of 108 patients treated for a first relapse of a FIGO stage III ovarian cancer was retrospectively included from December 1999 to November 2004. Each patient was treated with platinum-based chemotherapy in case of late (>6 months) relapse and with salvage chemotherapy without platinum in case of <6 months relapse. For statistical analysis the studied parameters were age, histological subtype, the completeness of initial surgery, disease-free period, localization of the relapse, clinical response to second-line chemotherapy, the completeness of secondary cytoreductive surgery (SCS) when it was performed. RESULTS: Median follow-up from the first relapse was 40 months. From the 108 patients, 35 underwent SCS. Median overall survival from the first relapse was 13 months in case of no SCS or non-optimal SCS and 35 months for patient with an optimal SCS (p = 0.006). In a multivariate analysis age, disease-free period, the clinical presentation of the relapse, completeness of SCS and response to second line chemotherapy appeared to be independent prognostic factors. CONCLUSIONS: Prognostic factors of ovarian cancer relapse are directly or indirectly linked with the feasibility of a complete SCS. Thus in the case of an ovarian cancer relapse, the feasibility of SCS must be considered in order to give the patient the best chance to experience its complete removal.

An atypical case of X-linked lymphoproliferative disease revealed as a late cerebral lymphoma.

X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency, partially characterized by a defect in cytotoxicity to Epstein-Barr virus. This viral infection is therefore often fatal in affected boys, whilst a variety of immune disorders or proliferative diseases may occur in surviving patients. We report an atypical case of a 41year-old male who presented with a primitive B-cell cerebral lymphoma, revealing an XLP. This presentation was unusual because of its late onset, the broad spectrum of the familial characteristics, its initial presentation as a cerebral lymphoma, and the occurrence of B-cell alymphocytosis associated with a-gamma-globulinemia.

Validation of UBE2C protein as a prognostic marker in node-positive breast cancer.

BACKGROUND: We recently identified and validated UBE2C RNA as a prognostic marker in 252 node-positive (N+) breast cancers by means of a microarray study. The aim of this study was to validate UBE2C protein as a prognostic marker in N+ breast cancer by immunohistochemistry (IHC). METHODS: To this end, 92 paraffin-embedded blocks were used. The impact of UBE2C IHC value on metastasis-free survival (MFS) and overall survival (OS) was evaluated and compared with Ki-67 and Nottingham prognostic index (NPI) performances. RESULTS: In accordance with genomic data, UBE2C IHC had a significant impact both on MFS and OS (hazard ratio=6.79 - P=0.002; hazard ratio=7.14 - P=0.009, respectively). Akaike information criterion proved that the prognostic power of UBE2C IHC was stronger than that of Ki-67 (and close to that of NPI). Furthermore, multivariate analyses with NPI showed that, contrary to Ki-67 IHC, UBE2C IHC remained an independent factor, both for MFS (adjusted P=0.02) and OS (adjusted P=0.04). CONCLUSION: We confirmed that UBE2C protein measured by IHC could be used as a prognostic marker in N+ breast cancer. The potential predictive interest of UBE2C as a marker of proteasome activity needs further investigations.

[Prognostic and predictive factors for gliomas in adults]. / Facteurs pronostiques et prédictifs de réponse des gliomes cérébraux de l'adulte.

Malignant gliomas are the most prevalent type of primary brain tumor in adults. They are classified into astrocytomes, oligodendrogliomes and oligo-astrocytomes on the presumed cell of origin. They are then classified according to their degree of malignancy into low-grade gliomas (I and II) and high-grade gliomas (III an IV) according to WHO classification. Conventional therapy includes surgery, radiotherapy and chemotherapy and is mostly palliative. Because patients with a same histologic diagnosis have variable outcomes, there is a need to develop better prognostic markers to predict tumor behaviour and response to therapy. For patients with low-grade gliomas, several clinical parameters affect prognosis and therapeutic options: histological type, tumor measurements, young age, performance status. Prognostic scores have been established based on a combination of these different clinical factors. For high-grade tumors, prognostic and predictive molecular markers have been identified. The combined loss of 1p and 19q is strongly correlated with the oligodendroglial phenotype and is associated with both chemotherapeutic response and prolonged overall survival in anaplastic (grade III) oligodendrogliomas treated with PCV chemotherapy and probably with temozolomide. Many glioblastomas have dysregulated epidermal growth factor receptor and among them, the co-expression of the mutant receptor subtype EGFRvIII. The clinical significance of these EGFR alterations is still debated. Nevertheless, co-expression of EGFRvIII and PTEN seem to be predictive factor of response to EGFR inhibitors currently tested in glioblastomas. In addition, the MGMT-methylation status is an independent predictor for glioblastoma patients treated with an alkylating agent: the epigenetic inactivation of the DNA repair gene MGMT is associated with a better response to chemotherapy and a better outcome. This status may have important implications for the design of future trials.

[Cervical pathology: significance and therapeutic impact of margin status]. / La notion de marge d'exérèse dans le contexte de la pathologie du col utérin : définitions et impact thérapeutique.

Margin status in cervical pathology is one of most important predictive factor of recurrent disease. Even if management of surgical biopsy is standardized, quality of surgical procedure is fundamental. Frozen section can be realise in order to complete surgical procedure if margins are involved. Extemporaneous exam of endocervical margin during conservative surgery and vaginal cuff during radical surgery is a precious information for surgeon. Endocervical status for conization, parametrial and vaginal margins have been reported to be a factor predictive of residual disease. During radical trachelectomy, margins involvment of one of these three topographic zone is an important predictive factor of recurrent disease and can be an obstacle to preserve fertility.

Prognostic impact of syndecan-1 expression in invasive ductal breast carcinomas.

Carcinoma cells lack syndecan-1 expression when they are transiting from an epithelial to a less-differentiated mesenchymal phenotype (epithelial-mesenchymal transition, EMT). Furthermore, a shift of syndecan-1 expression from malignant epithelial cells to reactive stromal cells has also been observed during progression of many carcinomas. Finally, epithelial and/or stromal syndecan-1 expression is of prognostic value in many carcinomas. Because recent results are contradictory in breast carcinomas, we have re-evaluated the prognostic significance of syndecan-1 expression in a cohort of 80 patients with invasive ductal breast carcinomas. The tumours from 80 patients diagnosed with invasive ductal breast carcinomas were used to construct a tissue microarray, which was stained with syndecan-1 by immunohistochemistry. We correlated syndecan-1 expression with clinicopathologic parameters and relapse-free survival (RFS). Exclusive epithelial expression of syndecan-1 is observed in 61.25% of the patients, whereas exclusive stromal expression is observed in 30% of the patients. Only 8.75% of the patients had both stromal and epithelial expressions of syndecan-1. A significant correlation was found between the loss of syndecan-1 epithelial expression and the syndecan-1 stromal expression with high grade of malignancy (P=0.011). The loss of syndecan-1 epithelial expression is correlated with RFS (P=0.001). Using multivariate Cox analysis, loss of epithelial syndecan-1 expression was the only prognostic indicator (P<0.001). We concluded that the loss of syndecan-1 epithelial expression was of strong prognostic value in breast carcinomas.

Increase in PGE2 biosynthesis induces a Bax dependent apoptosis correlated to patients' survival in glioblastoma multiforme.

Prostaglandin E(2) plays multiple roles both in the physiology and the physiopathology of human brain, which are not completely understood. We have identified in a subset of human glioblastoma multiforme (GBM) tumors, the most common form of adult brain cancer, an increased expression of mPGES-1, the enzyme which catalyses the isomerization of PGH(2) into PGE(2) downstream of cyclooxygenase 2 (COX-2). The sensitivity of primary cultures of GBM to apoptosis was augmented by the overexpression of mPGES-1, whereas the knockdown of its expression by shRNA decreased the apoptotic threshold in vitro and stimulated tumor growth in vivo. Adding extracellular PGE(2) in the culture medium failed to reproduce mPGES-1 effect on the cell viability in vitro. However, the intracellular injection of PGE(2) induced a dose-dependent apoptosis in GBM cultures, which was dependent on the presence of Bax, a pro-apoptotic protein. We show that PGE(2) physically associates with Bax, triggering its apoptotic-like change in conformation and its subsequent association with mitochondria. Our results raise questions about the role of PGE(2) in the control of apoptosis and in its potential impact in central nervous system pathologies.

[Diagnosis of flat epithelial atypia (FEA) after stereotactic vacuum-assisted biopsy (VAB) of the breast: What is the best management: systematic surgery for all or follow-up?]. / Lésions de métaplasie cylindriques atypiques (MCA) diagnostiquées par macrobiopsies assistées par aspiration: opportunité d'une exérèse chirurgicale?

OBJECTIVE: FEA lesions group two histological types: columnar cell hyperplasia with atypia (CCHA) and columnar cell change with atypia (CCA). The increasing use of VAB has resulted in increased detection of isolated FEA lesions. The aim of this study was to define the best management possible for these patients: which cases may not need excision? MATERIAL AND METHODS: From our database of 780 VABs carried out from 2000 to 2004, 59 patients with FEA were diagnosed. Cases in which no surgery was performed or all features were not available were excluded, thus excluding 19 cases. Forty patients with FEA were included. We reviewed clinical and mammographic characteristics, histological biopsy, and the corresponding surgically excised tissue features. RESULTS: VAB yielded 25 cases of CCHA and 15 cases of CCA. Surgery revealed seven ductal carcinoma cases (four invasive, three in situ); nine benign lesions, and 24 with atypia (19 FEA and six atypical ductal hyperplasia). We found two features related to the risk of cancer: the presence and the size of hyperplasia. All carcinomas were found within the CCHA lesions. No cancer was yielded when size was less than 10 mm within CCA lesions and lesions that were totally removed. CONCLUSION: We recommend surgical excision when CCHA greater than 10 mm is found on the VAB or it is incompletely removed. CCA lesions or CCHA less than 10 mm or totally removed may obviate systematic surgery.

Phosphohistone H3 labelling for histoprognostic grading of breast adenocarcinomas and computer-assisted determination of mitotic index.

BACKGROUND: Microscopic evaluation of mitotic figures is a routine procedure in the assessment of the histoprognostic grade of tumours. Nevertheless, their count may be fraught with difficulties. As histone H3 phosphorylation at serine 10 is closely linked to chromosomal condensation, a new monoclonal antibody directed to phosphorylated histone H3 (PPH3) was recently proposed to detect mitotic cells. AIM: To test the reliability of this antibody in detecting and counting mitotic figures in sections of breast adenocarcinomas, because of the importance of mitotic count in histoprognostic grading. METHODS: The pattern of PPH3 staining in formalin-fixed paraffin wax-embedded tissues, including normal tissues and a series of 39 breast adenocarcinomas, was examined. A new computer-assisted method was also developed for determining the mitotic index. RESULTS AND CONCLUSIONS: In all tissues tested, PPH3-labelled mitotic figures were easily detected, allowing a rapid identification of the area of highest mitotic activity. In breast carcinomas, a strong correlation was observed between PPH3-stained and haematoxylin and eosin-stained mitotic counts (r = 0.86, p<0.0001). Counting of prophase nuclei that coexpress cyclin B1, a marker of the G2/M phase, was possible by PPH3 staining; its accuracy led us to reconsider the tumour grade in three cases. Finally, an automatic computer-assisted method was designed for assessing mitotic index with confocal microscopy and image-analysis software.

Supratentorial primitive neuroectodermal tumours of the brain: multidirectional differentiation does not influence prognosis. A clinicopathological report of 18 patients.

AIMS: To examine the clinical and pathological characteristics of supratentorial primitive neuroectodermal tumours (PNETs) in a retrospective series of 18 patients, according to the strict definition of the World Health Organization classification of tumours that excludes other types of malignant embryonal tumours of the brain. METHODS AND RESULTS: Eleven children and seven adults with supratentorial PNETs were diagnosed between 1993 and 2002 and their medical records were reviewed. An immunohistochemical study was performed on formalin-fixed paraffin-embedded tissue of 18 primary tumours and five recurrences with antibodies for neuronal (neuron specific enolase, synaptophysin, neurofilament, chromogranin A), epithelial [epithelial membrane antigen (EMA), cytokeratin], glial [glial fibrillary acidic protein (GFAP)], muscle (desmin, h-caldesmon, alpha-smooth muscle actin, myogenin) differentiation and with two anti-CD99 antibodies. All tumours showed at least one neuronal marker except chromogranin A; a variable number of cells were GFAP+ or EMA+ in 18/23 tumours. Six primary tumours and one recurrence were positive for cytokeratin and/or one muscle antigen except myogenin. CD99 was observed in 33% of the cases. The mean duration of overall survival was 20 months. The estimated overall survival rates were 61% at 1 year, 29% at 2 years, and 18% at 3 years. Two factors of poor prognosis were identified by univariate analysis: a positive cerebrospinal fluid cytology at diagnosis and the absence of complete resection. No distinct immunophenotype was statistically related to survival. CONCLUSIONS: A multidirectional differentiation is a frequent event in supratentorial PNETs but has no apparent influence on the outcome of this aggressive neoplasm.