Exclusive surgical approach for facial arteriovenous malformations in precarious conditions.

Arteriovenous malformations (AVMs) are high-flow vascular lesions that does not regress spontaneously. They are located in the cranio-facial region in 50% of cases. Most of the time, the management of these lesions is a combination of surgery and vascular embolization. However, when the conditions are precarious, even without access to embolization, it's possible to treat some of those lesions with safety. We report four cases of patients suffering from cranio-facial AVM, treated exclusively by surgery during humanitarian missions.

Strengthening human genetics research in Africa: report of the 9th meeting of the African Society of Human Genetics in Dakar in May 2016.

The 9th meeting of the African Society of Human Genetics, in partnership with the Senegalese Cancer Research and Study Group and the Human Heredity and Health in Africa (H3Africa) Consortium, was held in Dakar, Senegal. The theme was Strengthening Human Genetics Research in Africa. The 210 delegates came from 21 African countries and from France, Switzerland, UK, UAE, Canada and the USA. The goal was to highlight genetic and genomic science across the African continent with the ultimate goal of improving the health of Africans and those across the globe, and to promote the careers of young African scientists in the field. A session on the sustainability of genomic research in Africa brought to light innovative and practical approaches to supporting research in resource-limited settings and the importance of promoting genetics in academic, research funding, governmental and private sectors. This meeting led to the formation of the Senegalese Society for Human Genetics.

Le 9ème congrès de la Société Africaine de Génétique Humaine, en partenariat avec le Groupe d'Etude et de Recherche sur le Cancer (GERC) et le Consortium H3Africa, s'est tenu à Dakar, au Sénégal. Le thème était «Renforcer la recherche en Génétique Humaine en Afrique¼. Les 210 participants sont venus de 21 pays africains et de six non africains. L'objectif était de valoriser la génétique et la génomique à travers l'Afrique avec comme but ultime d'améliorer la santé des populations, et de promouvoir les carrières des jeunes chercheurs Africains. Une session sur la pérennité de la recherche génomique a révélé des approches innovantes et pratiques supportant la recherche dans des contextes de ressources limitées et l'importance de promouvoir la formation universitaire en génétique, le financement de la recherche par les gouvernements et le privé. Ce congrès conduisit à la création de la Société Sénégalaise de Génétique Humaine.

[IgG responses to candidate malaria vaccine antigens in the urban area of Dakar (Senegal): evolution according to age and parasitemia in patients with mild symptoms]. / Analyses des réponses IgG dirigées contre des antigènes candidats vaccins dans le paludisme urbain non aggravé à Dakar (Sénégal): variations suivant l'âge et les densités parasitaires.

Malaria remains a major problem in African countries despite substantial decreases in morbidity and mortality due to sustained control programs. Studies for the evaluation of qualitative or quantitative Ab responses to key targets of anti-plasmodium immunity were mostly done in rural endemic setting compared to urban area. In a cohort of 200 patients with mild malaria and living in Dakar, we analyze total and subclasses IgG responses to a panel of P. falciparum blood stage antigens: MSP1p19, MSP3, EB200, GST-5 and R23. A mean age of 15 yrs (4 to 56 yrs) and parasitemia between 0.1 to 17% were found. Levels of IgG anti-MSP3 were higher in patients with low parasitemia (≤1%) and appear negatively correlated to parasite densities (Rho =. 0.54; p= 0.021). This correlation is more significant in children (≤ 15 yrs). In addition, an increase of IgG responses against MSP1p19 is highly observed in adults having a parasitemia less than 1%. In those patients, we find that IgG1 subclasses were predominant (p <0.01). Our study shows an association between Ab responses and parasitemia. This association is dependant to IgG anti-MSP3 in children and IgG anti-MSP1p19 in adults living in urban area.

[Profile of cranio-cerebral trauma and spinal cord trauma related road accidents in Guinea]. / Profil des traumatismes crânio-encéphalique et vertébro-médullaire liés aux accidents de la voie publique en Guinée.

OBJECTIVE: To describe the profile of the patient injured in traffic accidents and having a cranio-cerebral trauma (CCT) or spinal cord trauma (SCT). METHOD: Cross-sectional and retrospective survey of records management in 2829 road accident victims with CCT and/or a SCT and admitted to a hospital in Guinea between 1st January and 31st December, 2009. The profile was described by: the sociodemographic data, the circumstances of the accident and the clinical, therapeutic and follow-up data. RESULTS: For an average age of 27.1±12.7 years, the location of the trauma was cranio-cerebral in 82.0% of cases, spinal in 8.9% of cases and mixed in 9.1%. A large proportion of CCT (66.3%) and mixed trauma (63.1%) comes from to two-wheeled vehicles, while the large proportion of SCT (54.2%) is attributable to vehicles with four wheels. The Glasgow Coma average was 13.2±2.6 at admission, 21.7% of the victims are taken in charge beyond the first 12hours after the accident. Only 19.2% of patients underwent a surgical treatment with a hospital mortality ranging from 3.3 % (TVM) to 7.7% (mixed). CONCLUSION: CCT and SCT are characterized by an age under 30 years and male predominance. The support care suffers greatly from the unbalanced distribution of qualified personnel on the national territory and the lack of material means.

Proteomic study of calpain interacting proteins during skeletal muscle aging.

Aging is associated with a progressive and involuntary loss of muscle mass also known as sarcopenia. This condition represents a major public health concern. Although sarcopenia is well documented, the molecular mechanisms of this condition still remain unclear. The calcium-dependent proteolytic system is composed of calcium-dependent cysteine proteases named calpains. Calpains are involved in a large number of physiological processes such as muscle growth and differentiation, and pathological conditions such as muscular dystrophies. The aim of this study was to determine the involvement of this proteolytic system in the phenotype associated with sarcopenia by identifying key proteins (substrates or regulators) interacting with calpains during muscle aging. Immunoprecipitations coupled with proteomic analyses and protein identification by mass spectrometry have been undertaken. Reverse co-immunoprecipitation, cellular colocalisation by confocal microscopy and calpain-dependent in vitro proteolysis of several of the identified proteins have been also carried out. We identified ATP synthase subunit alpha and alpha actinin 3 as key partners of calpains during muscle aging. Such interactions would suggest that calpains are implicated in many processes altered during aging including cytoskeletal disorganisation and mitochondrial dysfunction.

[Do commercial sex workers who discuss treatment with family and friends adhere to it better?]. / Communiquer avec son entourage sur son traitement aide-t-il les femmes impliquées dans le commerce du sexe à l'observer?

INTRODUCTION: The number of HIV trials in Africa is increasing, and they target population groups with high HIV incidence, such as sex workers. Little information, however, is available about the adherence to long-term therapy among such marginalized groups with few economic resources and poor social and family support. A project called "Yerelon" ("know herself" in the Dioula language) began in 1998 in Bobo-Dioulasso to improve the health of women involved in commercial sex through STI/HIV prevention and care adapted to them. This study was conducted before introducing long-term treatment to the population, to assess the effect of communication with those around them on the capacity of these vulnerable women to adhere to drug prescriptions. METHODS: The study was based on interviews conducted during the pilot phase of a 3-month trial of vitamins with potential participants. It concerned two groups of women: one group was infected with HIV (N = 22), the other was not (N = 20); all women in both groups were infected by HSV-2, however. For 5 weeks, the two psychologists of the study team in charge of adherence assessment carried out weekly in-depth interviews with the participants. The qualitative data analysis was organised around several themes. The data were related to aspects of communication with family and friends, serologic results, and adherence. RESULTS: According to our definition of communication about treatment, 20 participants communicated with their family and friends; adherence was good for all but three of them. Women who reported that they were married or living with someone (7/42) nearly all spoke about the study treatment (06/07) with him. Of 16 participants living in a family, 10 communicated with them about the treatment. On the other hand, as seems logical, single women who lived alone spoke less often about the treatment with family and friends (04/19). Talking about the treatment did not appear to involve the family or friends in the treatment; no one reminded any participant, whether she lived alone or in a family, to take her medicine. Nor did this discussion seem "helpful" to any of the women. Twenty-two participants hid the study treatment from family and friends; adherence was good for all but two of these. Social management of the treatment was related to HIV serologic status and relationships with family and friends. Concern about gossip about HIV status made it difficult to integrate the treatment into conversation. Those who did not agree to communicate with their family about the treatment did not even take the drug in the sight of the others. Sometimes, refusal to communicate was aimed at avoiding disapproval when the family did not have a favorable perception of prolonged treatment. Hiding the treatment was not an obstacle to good adherence. Adherence was related to perception of the treatment more than to communication about it. CONCLUSION: Adherence was similar in cases with and without communication. It appeared that these marginalized women, without social networks, were able to adhere correctly to a long-term treatment. To minimize the risks of non-adherence, the support system planned must take into account the factors influencing perceptions of the drug. Specific psychological support centered on the relation with the drug appears necessary during treatment initiation and follow up.

[Nocardia brain abscess: features, therapeutic strategies and outcome]. / Abcès cérébraux àNocardia: caractéristiques radiocliniques et prise en charge thérapeutique.

BACKGROUND AND PURPOSE: Nocardia species is an aerobic soil-saprophyte bacterium, responsible for rare opportunistic infections, mainly reported in immunocompromised patients. Nocardia brain abscess accounts for 1 to 2% of cerebral abscesses. Prognosis is poor. METHODS: We describe clinical, radiological and bacteriological findings along with therapeutic aspects for five patients and review the literature on Nocardia cerebral abscess. RESULTS: The clinical features of Nocardia brain abscess are insidious and nonspecific, occurring frequently with a medical background of obvious or latent immunodeficiency; fever, if any, is observed subordinate to extracerebral nocardiosis. Computerized tomography scan and conventional magnetic resonance (MR) scan show lesions with a necrotic core and multilobed thick walls enhancing after injection of gadolinium or iodine. Abscesses are mainly located in the brain stem, basal ganglia and cerebral cortex of the frontal, parietal and occipital lobes; cerebellar and spinal locations are uncommon. MR diffusion-weighted imaging with calculation of apparent diffusion coefficient and proton MR spectroscopy can provide additional data for accurate differential diagnosis between abscess and other necrotic lesions, such as tumor and cyst formations. Bacteriological identification has progressed with advances in molecular microbiology: 16S rRNA sequencing, allowing a more rapid routine identification of Nocardia strains from clinical samples. Clinical management of patients with a Nocardia brain abscess relies upon early use of intravenous antibiotics adapted to the strains identified and their susceptibility. Most Nocardia strains display susceptibility to cotrimoxazol, amikacin and linezolid, but develop beta-lactamase activity. CONCLUSIONS: Early pus samples, obtained by biopsy or surgical resection, are needed to establish a certain bacteriological diagnosis and initiate appropriate intravenous antibiotics.

[Neurosensory disorders and functional impairment after bilateral sagittal split osteotomy: role of the anatomical situation of the alveolar pedicle in 76 patients]. / Troubles de la sensibilité consécutifs aux ostéotomies sagittales des branches montantes de la mandibule: rôle de la position du pédicule alvéolaire chez 76 patients.

INTRODUCTION: Bilateral sagittal split osteotomy (BSSO) of the mandibular ramus is the most frequent orthognatic surgery. The risk of neurosensory disorders remains high even their incidence varies according to numerous publications. The anatomical location of the alveolar pedicle seems to be one of the most important factors in these disorders. The aim of this study was to determine its exact role. MATERIAL AND METHOD: We performed a retrospective study on 76 patients and 152 osteotomy sides, all of them operated according to the Epker technique by the same surgeon between 2000 and 2004. For each operative side we noted the position of the inferior alveolar nerve during the split: Type I entirely in the internal cortical bone, Type II partially in the external cortical bone, Type III mostly or completely in the external cortical bone. The neurosensory disorders were recorded during clinical examination and simply classified into two categories: "absent" or "present". The outcome was noted during the postoperative follow-up at D1; D15; M1,5, M6, and M12. After that, it was documented through a written questionnaire or telephone conversation. RESULTS: Since there was no difference between the right and the left sides, the study enclosed all of the operative sides together (152). The anatomical distribution was: 97 Type I (63.8%), 28 Type II (18.4%), and 27 Type III (17.8%). Immediate postoperative neurosensory disorders (D1) occurred on 74.3% of sides, with important significant differences between Type I (64.9%) on one hand, Type II (89.2%) and Type III (92.6%) on the other hand. At one year of follow-up, the rate of neurosensory disorders was 20.4% with also a difference between Type I (13.4%) and Types II and III (35.7% and 29.6%). DISCUSSION: The anatomical location of the alveolar pedicle seems to be important. This study confirms previously published studies and raises the question of CT scan assessment before performing BSSO.

[Therapeutic management of tics in Tourette's syndrome]. / Prise en charge thérapeutique des tics dans la maladie de Gilles de Tourette.

Tourette's syndrome is a neuropsychiatric disorder characterised by both involuntary movements, tics, and psychiatric symptoms, attentional deficit disorder, hyperactivity, obsessive compulsive symptoms..., and can be the cause of major disability. Over the past 30 years, several types of treatment have been proposed for the treatment of tics in Tourette's Syndrome, ranging from psychotherapeutic approaches to neurosurgery. The education of the patient and his entourage is fundamental and must be offered to all patients. Psychotherapy does not directly improve the tics but contributes to a better adjustment of both patient and carers to his disability. The decision to start a course of drug therapy depends largely on the impact of the patient's tics on his personal life. Drug treatment relies on neuromodulators acting on a variety of neural systems and whose efficacy has been rarely demonstrated. The literature shows that the latest generation of dopaminergic antagonists have the highest benefit/risk ratio. Recently, deep brain stimulation, by modulating neuronal activity in structures involved in the pathophysiology of the disease, has become a promising therapeutical approach, producing a marked decrease in the severity of tics over that obtained with other treatments.

Unidirectional ocular flutter.

Ocular flutter is a rare abnormal eye movement consisting of irregular bursts of to-and-fro bidirectional horizontal saccades and is frequently encountered in association with cerebellar symptoms. We present a patient with a probable post-infectious ocular flutter that exhibited characteristics not previously reported in the literature. Bursts of ocular flutter consisted almost exclusively of initial rightward saccades and were clearly influenced by orbital eye position and the presence of a visual stimulus. The most recent models of saccadic oscillations do not provide an explanation for such atypical features, especially for the systematic directional bias. Based on existing experimental data, we propose that dysfunction of vermal pause neurons in an unstable saccade network could account for such atypical characteristics.

C-kit expression in high-risk breast cancer subgroup treated with high-dose or conventional dose-dense chemotherapy.

The proto-oncogene c-kit is known to be expressed in poorly differentiated breast cancer. In this study, we retrospectively evaluated the prognostic and predictive impact of c-kit in a high risk subgroup of breast cancer patients (>9 axillary node metastases) who received high-dose (HDCT) or dose-dense (DDCT) conventional chemotherapy and correlated these findings with the expression of the basal-type markers CK5 and CK 17, estrogen (ER) and progesterone (PR) receptor, Her-2/neu and MIB 1. C-kit, CK5, CK17, ER, PR, Her-2/neu and MIBI expression was evaluated immunohistochemically using tissue microarrays containing breast cancer samples from 236 patients who were randomized to the WSG AM01 trial (median follow-up of 60 months). There was a significant overall survival (OS) benefit for patients receiving HDCT compared to DDCT (p = 0.027). C-KIT expression was found in 12 % of all breast cancers and correlated with a poorer OS in multivariate analysis (p = 0.051). Furthermore, c-kit correlated with high grade (p = 0.019), CK5- and CK17-positivity (p <0.0001 and p = 0.001, respectively) and ER- and PR-negativity (p = 0.04 and p = 0.008, respectively). In contrast to CK5 and CK17, patients with c-kit positive breast cancers revealed no benefit from high-dose chemotherapy. These findings underline that c-kit expression represents an independent negative prognostic marker in high-risk breast cancer. Correlation with CK5 +/CK17+ and ER-/PR-suggests that c-kit positive carcinomas are at least partly of basal-type.

Endosonographic and histopathological staging of extrahepatic bile duct cancer: time to leave the present TNM-classification?

OBJECTIVES: The discrepancy between high rates of sensitivity, specificity, and accuracy for intraductal ultrasonography (IDUS) in extrahepatic bile duct carcinoma and the failure to depict different wall layers as defined by the TNM classification have not yet been elucidated sufficiently. METHODS: In a prospective study, endosonographic images were correlated with histomorphology including immunohistochemistry. Using IDUS, we examined fresh resection specimens of patients who had undergone pancreato-duodenectomy. For histological analysis, the formalin-fixed and paraffin-embedded specimens were stained by hematoxylin-eosin, elastica-van-Gieson, and immunohistochemically by smooth muscle-actin. To confirm our hypothesis, further cases from the archives were analyzed histopathologically and immunohistochemically. RESULTS: The various wall layers of the extrahepatic bile duct as described by the International Union Against Cancer are neither histomorphologically nor immunohistochemically consistently demonstrable. Especially, a clear differentiation between tumor invasion beyond the wall of the bile duct (T2) and invasion of the pancreas (T3) by histopathological means is often not possible. Endosonographic images using high-resolution miniprobes similarly confirm the difficulty in imaging various layers in the bile duct wall. CONCLUSIONS: Most adaptations made by the sixth edition of the TNM classification accommodate to the endosonographic and most of the histopathological findings as demonstrated in our study. In contrast to the new edition, however, our findings suggest to combine T2- and T3-staged tumors into one single class leading to clarification, and improved reproducibility of histopathological staging.

Time- and dose-dependent changes of intracellular cytokine and cytokine receptor profile of Ewing tumour subpopulations under the influence of ionizing radiation.

PURPOSE: Cytokines and their corresponding cell surface receptors are involved in intercellular signalling pathways and in the radioresistance of normal and malignant cells. The aim was the characterization of the expression of intracellular cytokines, their receptors and apoptosis-associated markers under the influence of radiation. MATERIAL AND METHODS: Two Ewing tumours were characterized in vitro before and 4, 24 and 72 h after radiation with 5 and 10 Gy, and in vivo 4, 6 and 15 days after radiation with 5 and 30 Gy by five parameter flow cytometry. Direct fluorescence-conjugated antibodies directed against intracellular cytokines (interferon-gamma, tumour necrosis factor [TNF]-alpha, interleukin 1) and their receptors (CD119, CD120a, CD121a) were used. Annexin V and 7-amino-actinomycin D were used to identify radiation-induced apoptosis. RESULTS: Inter- and intra-individual heterogeneities were identified by the expression of cytokine receptors and the intracellular cytokine profile before radiation. Time- and dose-dependent up-regulation of the cytokines TNF-alpha and interleukin 1 were found in vitro. In vivo, an up-regulation of CD120a and CD121a was detectable on tumour cell subpopulations. For interferon-gamma and CD119, no changes were seen. CONCLUSIONS: The observed radiation-induced changes of cytokine and receptor profile are an indication for complex intercellular interactions in view of radioresistance-associated mechanisms between cell populations within one individual tumour. The observed heterogeneous response on radiation might have therapeutic implications for an individualized therapy based on combined radiation and cytokine modulation, defined by flow cytometric characterization of markers potentially informative for radioresistance.

Effect of radiation on Ewing tumour subpopulations characterized on a single-cell level: intracellular cytokine, immunophenotypic, DNA and apoptotic profile.

PURPOSE: Adhesion molecules, cytokines and their corresponding cell-surface receptors are involved in intercellular signalling pathways, radioresistance and metastasis-mediating mechanisms of malignant cells. The aim was the characterization of changes in the marker profile of Ewing tumour cell subpopulations under the influence of radiation. MATERIALS AND METHODS: Three Ewing tumours were characterized in vitro and in vivo in a xenograft model before and after radiation by five-parameter flow cytometry. Antibodies directed against cell surface and intracellular antigens, apoptosis-associated markers and the DNA dye 7-aminoactinomycin D were used. RESULTS: Tumour cell subpopulations were identified by expression of adhesion molecules and cytokine receptors, intracellular cytokines, apoptotic markers and DNA content. Heterogeneous changes of flow cytometric profile were identified on tumour cell subpopulations after radiation. CONCLUSIONS: The changed profile of tumour cells under radiation might be associated with biological changes of tumour subpopulations in view of radioresistance and metastatic potential and might be useful to identify intercellular regulation mechanisms and to define parameters being predictive for a response to therapy.

Secretory carcinoma of the breast: a genetically defined carcinoma entity.

Secretory carcinomas (SBC) are characterized by their characteristic histomorphology and more favorable prognosis compared to invasive ductal carcinoma of usual type (IDC). On this basis, 13 SBCs are evaluated by molecular and immunohistochemical (IH) methods. 13 SBCs and 4 IDCs were analyzed for ETV6-NTRK3 gene fusion by reverse transcriptase-polymerase chain reaction (RT-PCR) and by Fluorescence in situ Hybridization (FISH). 8 of 13 microdissected SBCs with evaluable DNA were evaluated for genetic alterations (GA) by comparative genomic hybridization (CGH). IH included estrogen-receptor (ER), progesterone-receptor (PR), Her-2/neu and Ki-67 (MIB-1) in all 13 cases. Molecular and immunohistochemical results in SBCs were compared with previous data regarding immunohistochemical and molecular characteristics of IDCs. 12 of 13 (92 %) SBC cases, but not IDCs expressed the ETV6-NTRK3 fusion gene which encodes a chimeric tyrosine kinase. Retroviral transfer of ETV6-NTRK3 (EN) into murine mammary epithelial cells resulted in transformed cells that readily formed epithelial tumors in nude mice. CGH revealed an average of 2.0 GAs (range 0-6), including recurrent gains of chromosome 8q and 1q and losses of 22q. Four SBCs were positive for ER and 2 were positive for PR. The mean MIB-1-labeling index was 11.4% (range: <1-34%). Her-2/ neu protein overexpression was detected in 1 case (score 3+). Compared to previous findings in IDCs, SBCs are characterized by the recurrent expression of ETV6-NTRK3 fusion gene, a relatively low number of GAs, low proliferative rate, infrequent Her-2/ neu protein overexpression and a lower rate of steroid hormone receptor expression. These results support the hypothesis that SBCs have immunohistochemical and genetic features that specifically distinguish them from IDCs.

Population-based genetic alterations in Ewing's tumors from Japanese and European Caucasian patients.

BACKGROUND: The incidence of Ewing's tumors (ETs) is lower in Asians or African-Americans than in Caucasians. PATIENTS AND METHODS: Japanese ETs were available for analysis of chromosomal aberrations by comparative genomic hybridization (n = 16) and for expression of chimeric EWS transcripts by reverse-transcriptase polymerase chain reaction (n = 11). These results in Japanese patients were compared with those of 62 ETs in European Caucasian patients registered in the European Intergroup Cooperative Ewing's Sarcoma Study. RESULTS: Japanese patients with ET had lower overall survival (P = 0.0446) and relapse-free survival (P = 0.0371) compared with European Caucasian patients. Ten of 11 Japanese ETs and 31 of 62 European Caucasian ETs had type I (EWS exon 7 to FLI1 exon 6) fusion transcripts. In Japanese ETs, the median numbers of chromosomal aberrations were 2.0 and 6.0 in 11 primary tumors and five relapsed tumors, respectively. In European Caucasian ETs, the median number of changes were 2.5 and 5.0 in 52 primary and 10 relapsed tumors, respectively. Frequent gains were 8q (38%), 8p (31%) and 12q (25%) in Japanese ETs and 8q (52%), 8p (48%) and 12q (19%) in European Caucasian ETs. Frequent losses were 19q (44%), 19p (38%) and 17p (25%) in Japanese ETs and 16q (21%), 19q (18%) and 17p (15%) in European Caucasian ETs. The incidence of losses of 19p (P = 0.0215) and 19q (P = 0.0277) were significantly higher in Japanese ETs than in European Caucasian ETs. An amplification (1p33-p34) was observed in only one Japanese ET. CONCLUSIONS: Japanese patients with ET in this study had a worse prognosis than European Caucasian patients. In molecular genetic analyses, Japanese ETs had a higher frequency of loss of chromosome 19 than European Caucasian ETs. Different genetic aberrations may explain the different incidences and prognoses of ET between Caucasian and Japanese patients.

Ductal epithelial proliferations of the breast: a biological continuum? Comparative genomic hybridization and high-molecular-weight cytokeratin expression patterns.

According to current concepts, benign proliferative breast disease (BPBD) is a direct precursor of breast cancer, in a spectrum ranging from ductal hyperplasia to overtly invasive carcinoma. In this study, comparative genomic hybridization (CGH) was used to screen ductal hyperplasia and other BPBD lesions and ductal carcinoma in situ (DCIS) for common genomic abnormalities, to test the relationship between these hyperplastic and neoplastic lesions. Immunohistochemistry for cytokeratin 5/6 was used as a diagnostic adjunct to distinguish ductal hyperplasia from DCIS. A total of 42 cases of BPBD comprising ductal hyperplasia of the usual type (n=14), papilloma (n=22), tubular adenoma (n=3), and adenosis (n=3), as well as 52 cases of DCIS, were studied. All cases of BPBD consistently displayed the presence of a subpopulation of cytokeratin 5/6-expressing basal-type cells within the proliferative lesion, whereas all of the non-high-grade and most of the high-grade DCIS lesions lacked cytokeratin 5/6-positive cells. Whereas gross genomic alterations, as determined by CGH, were undetectable in BPBD, distinct genetic changes characterized all cases of DCIS, with one exception. These results confirm the usefulness of cytokeratin 5/6 immunohistology in the diagnosis of BPBD and neoplastic breast lesions and support the view that BPBD and DCIS are not closely related entities and that BPBD is not an obligate direct precursor of DCIS.