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1.
Breast Cancer Res Treat ; 168(1): 189-196, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29159760

RESUMEN

PURPOSE: Evidence suggests that premenopausal obesity decreases and postmenopausal obesity increases breast cancer risk. Because it is not well known whether this is subtype dependent, we studied the association between body mass index (BMI) and age at breast cancer diagnosis, or the probability of being diagnosed with a specific breast cancer phenotype, by menopausal status. METHODS: All patients with non-metastatic operable breast cancer from the University Hospital Leuven diagnosed between January 1, 2000 and December 31, 2013 were included (n = 7020) in this cross-sectional study. Linear models and logistic regression were used for statistical analysis. Allowing correction for age-related BMI-increase, we used the age-adjusted BMI score which equals the difference between a patient's BMI score and the population-average BMI score corresponding to the patient's age category. RESULTS: The quadratic relationship between the age-adjusted BMI and age at breast cancer diagnosis (p = 0.0207) interacted with menopausal status (p < 0.0001); increased age at breast cancer diagnosis was observed with above-average BMI scores in postmenopausal women, and with below-average BMI scores in premenopausal women. BMI was linearly related to the probabilities of Luminal B and HER2-like breast cancer phenotypes, but only in postmenopausal women. The relative changes in probabilities between both these subtypes mirrored each other. CONCLUSION: BMI associates differently before and after menopause with age at breast cancer diagnosis and with the probability that breast cancer belongs to a certain phenotype. The opposite effect of increasing BMI on relative frequencies of Luminal B and HER2-like breast cancers suggests a common origin.


Asunto(s)
Índice de Masa Corporal , Neoplasias de la Mama/patología , Obesidad/epidemiología , Posmenopausia/metabolismo , Premenopausia/metabolismo , Adulto , Factores de Edad , Bélgica , Mama/metabolismo , Mama/patología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Obesidad/diagnóstico , Obesidad/metabolismo , Paridad , Estudios Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Factores de Riesgo
2.
Virchows Arch ; 466(4): 415-22, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25677978

RESUMEN

Clinical outcome of 23 patients with mixed endometrioid and serous endometrial carcinomas (mixed EEC-SC) was compared to that of pure endometrioid (EEC) and pure serous (SC) carcinomas. Hotspot mutation frequencies in KRAS, PIK3CA, PTEN, and TP53 and microsatellite instability (MSI) status were determined in mixed EEC-SC, as well as in their EEC and SC microdissected components separately, and alterations were compared to frequencies in pure EEC and SC. Relapse-free (RFS) and overall survival (OS) differed significantly between mixed EEC-SC and pure EEC and SC, revealing that outcome of mixed EEC-SCs was intermediate to that of pure EEC and pure SC. PTEN mutations were absent in pure SC, but occurred in 20 % of pure EEC, and 13 % of mixed EEC-SC. In contrast, TP53 mutations were more frequent in pure SC (17 %) and mixed EEC-SC (22 %) than in pure EEC (2 %). Mutations in mixed EEC-SC were shared by the two microdissected components in 30 %, whereas in 35 %, some mutations were component-specific. Mutation analysis confirms similarities between the EEC and SC components of mixed EEC-SC with pure EEC and pure SC, respectively. However, PTEN and KRAS mutations were more frequent in the SC component of mixed EEC-SC than in pure SC, while TP53 mutations were more frequent in the EEC component of mixed EEC-SC than in pure EEC. Presence of different clonal mutation pattern between EEC and SC components of mixed EEC-SC raises the possibility of divergent tumor heterogeneity or biclonal origin in some cases.


Asunto(s)
Carcinoma Endometrioide/genética , Cistadenocarcinoma Seroso/genética , Neoplasias Endometriales/genética , Neoplasias Complejas y Mixtas/genética , Anciano , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/patología , Cistadenocarcinoma Seroso/mortalidad , Cistadenocarcinoma Seroso/patología , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Neoplasias Complejas y Mixtas/mortalidad , Neoplasias Complejas y Mixtas/patología , Modelos de Riesgos Proporcionales
3.
Rev Med Liege ; 70(11): 550-6, 2015 Nov.
Artículo en Francés | MEDLINE | ID: mdl-26738266

RESUMEN

Gestational trophoblastic diseases include placental pathologies comprising fertilization abnormalities (hydatidiform moles) and malignant lesions (choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor). Due to their low incidence and heterogeneity, their diagnosis, management and treatment are not always optimal. Following the example of other European countries, a national registration system with two reference centers has been set up to guide physicians and patients and to propose individualized management. The centers offer their expertise through a systematic centralised pathology review by a panel of experts. HCG values are plotted in regression curves. In case of gestational trophoblastic neoplasia, an imaging work-up is proposed, from which the FIGO score and stage are derived and will guide the choice of treatment. Belgian centers offer a multidisciplinary approach, in partnership with the referent physician. More information for practitioners and patients is available on a web site: www.mole-chorio-bgog.eu, which also harbours a forum of discussion.


Asunto(s)
Enfermedad Trofoblástica Gestacional/epidemiología , Enfermedad Trofoblástica Gestacional/terapia , Sistema de Registros , Bélgica/epidemiología , Femenino , Enfermedad Trofoblástica Gestacional/clasificación , Humanos , Grupo de Atención al Paciente , Embarazo
4.
Ultrasound Obstet Gynecol ; 44(6): 722-4, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24816904

RESUMEN

Monochorionic (MC) twin pregnancies are at increased risk of adverse outcome because of the vascular anastomoses that connect the two fetal circulations. MC monoamniotic (MA) twins are at an even higher risk because of their almost universal cord entanglement and possible compression, which can cause an acute transfusion imbalance between the twins. Chorionicity and amnionicity should be determined during the first-trimester ultrasound examination to identify high-risk MC and MA twin pregnancies for which a fortnightly follow-up may improve outcome. Although this can be achieved readily by assessing and counting the membranes that separate the twins, some pitfalls may occur. We present our observations of two monozygotic twin pairs with an intermediate type of monodichorionic and monodiamniotic twin pregnancy. The first was recognized during the first-trimester scan and the second during the second-trimester scan.


Asunto(s)
Amnios/diagnóstico por imagen , Corion/diagnóstico por imagen , Embarazo Gemelar , Gemelos Monocigóticos , Ultrasonografía Prenatal , Adulto , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo
5.
Breast ; 23(4): 371-7, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24530094

RESUMEN

BACKGROUND: Invasive lobular breast cancer (ILC) is generally believed to have an increased risk for late relapse compared to invasive ductal breast cancer (IDC). However, the study most often referred to is a chemotherapy trial that mainly included node positive patients. We hypothesize that nodal status may influence the hazard of relapse since time of diagnosis differently in invasive ductal carcinoma (IDC) and ILC. METHODS: Primary operable breast cancer patients from our institution diagnosed between 2000 and 2009 were studied. Multivariable analysis and subgroup analyses were performed to assess whether ILC carries a different prognosis compared to IDC. SEER data were used for external validation. RESULTS: In lymph node negative patients, ILC carries a better prognosis regarding distant metastasis free interval (DMFI) (HR 3.242 (1.380-7.614), p = 0.0069) with a trend towards improved breast cancer specific survival (BCSS), over the entire study frame (UZ Leuven data). In lymph node positive patients, both DMFI (HR 0.466 (0.309-0.703), p = 0.0003) and BCSS (HR 0.441 (0.247-0.788), p = 0.0057) are significantly worse for ILC, especially after longer follow-up (>4-5 years) (UZ Leuven data). Similar results were found in the SEER cohort. Results remained identical when excluding screen detected cases (data not shown). CONCLUSION: The prognostic impact of lobular histology not only depends on time since diagnosis but also on nodal status. The general believe that ILC have compromised late-term outcome compared to IDC seems untrue for the majority ( = node negative) of ILCs.


Asunto(s)
Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/patología , Ganglios Linfáticos/patología , Recurrencia Local de Neoplasia/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Programa de VERF , Estadística como Asunto , Factores de Tiempo
6.
Ann Oncol ; 24(7): 1847-1852, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23680691

RESUMEN

BACKGROUND: Breast cancer remains the leading cause of female cancer death despite improvements in treatment and screening. Screening is often criticized for leading to overdiagnosis and overtreatment. However, few have attempted to identify overdiagnosed cases. PATIENTS AND METHODS: A large, consecutive series of patients treated for primary operable, screening-detected, breast cancer (n = 1610). Details from pathology and clinical reports, treatment and follow-up were available from our prospectively managed database. Univariate and multivariate Cox proportional models were used to study the prognostic variables in screening-detected breast cancers for distant metastatic and breast cancer-specific survival. RESULTS: We included 1610 patients. The mean/median follow-up was 6.0/6.0 years. Univariate analysis: tumor size, palpability, breast cancer phenotype and nodal status were predictors of distant metastasis and breast cancer-specific death. Multivariate analysis: palpability, breast cancer phenotype and nodal status remained independent prognostic variables. Palpability differed by breast cancer phenotype. CONCLUSION: Screening-detected breast cancer is associated with excellent outcome. Palpability, nodal status and breast cancer phenotype are independent prognostic variables that may select patients at increased risk for distant metastatic relapse and breast cancer-specific death. Overdiagnosed cases reside most likely in the nonpalpable node negative subgroup with a Luminal A phenotype.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/diagnóstico por imagen , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/secundario , Detección Precoz del Cáncer , Reacciones Falso Positivas , Femenino , Humanos , Metástasis Linfática , Mamografía , Persona de Mediana Edad , Análisis Multivariante , Palpación , Fenotipo , Pronóstico , Modelos de Riesgos Proporcionales , Carga Tumoral
7.
Breast ; 22(3): 254-62, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23566558

RESUMEN

Measuring CA15.3 serum levels in the early breast cancer setting is not recommended by current ASCO guidelines. In this large single center study, we assess the prognostic value of preoperative (n = 3746), postoperative (n = 4049) and change in (n = 3252) CA15.3, also across different breast cancer phenotypes. Preoperative, postoperative and change in CA15.3 were all significant (p = 0.0348, p < 0.0001, p < 0.0001 respectively in multivariate analysis) predictors of distant metastasis free survival. For breast cancer specific survival, only postoperative and change in CA15.3 were significant predictors (p < 0.0001 both). Multivariate prognostic models did not improve by incorporating information on preoperative CA15.3, but did improve when introducing information on postoperative CA15.3 for distant metastasis (p = 0.0365) and on change in CA15.3 for breast cancer specific survival (p = 0.0291). Change in CA15.3 impacts on prognosis (distant metastasis) differently in different breast cancer phenotypes. A decrease in CA15.3 may be informative of improved prognosis in basal like and HER2 like breast cancer.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Mucina-1/sangre , Anciano , Neoplasias de la Mama/química , Neoplasias de la Mama/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Periodo Posoperatorio , Periodo Preoperatorio , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Estudios Retrospectivos
8.
Placenta ; 33(8): 658-61, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22632806

RESUMEN

OBJECTIVE: We describe a case of chorangiocarcinoma, a complex lesion consisting of a trophoblastic proliferation within a chorangioma, presenting in a term placenta. MATERIALS AND METHODS: The lesion was diagnosed by ultrasound at a second trimester check-up after amniocentesis, performed because of increased combined risk at first trimester screening for trisomy 21. After uncomplicated vaginal delivery, a healthy child was born and the placenta was expelled spontaneously. RESULTS: Gross examination of the placenta showed a well-demarcated mass, bulging paracentrally from the fetal surface. Histology revealed a trophoblastic proliferation inside a chorangioma, consisting of multiple nodules with characters of focal multinucleation and pleomorphic cell nuclei, extensive central necrosis and high mitotic activity. Immunohistochemical staining showed strong intensity for hCG; Ki-67 (MIB-1) demonstrated a high proliferation index. Histopathological and immunohistochemical profile was compatible with a malignant trophoblastic proliferation. CONCLUSIONS: This is only the fifth reported case of so-called "chorangiocarcinoma" of the placenta (Table 1). However, histopathologically only one reported case was identical to ours. A proliferation of atypical trophoblast was observed inside a chorangioma, which formed as it were a shield around the trophoblast. No extravascular stromal invasion was present. Follow-up revealed no metastases, either in the mother or the child, up to 3 months after birth.


Asunto(s)
Placenta/patología , Complicaciones Neoplásicas del Embarazo/diagnóstico por imagen , Tumor Trofoblástico Localizado en la Placenta/diagnóstico por imagen , Neoplasias Uterinas/diagnóstico por imagen , Adulto , Femenino , Hemangioma/diagnóstico por imagen , Hemangioma/patología , Humanos , Placenta/diagnóstico por imagen , Embarazo , Complicaciones Neoplásicas del Embarazo/patología , Nacimiento a Término , Tumor Trofoblástico Localizado en la Placenta/patología , Ultrasonografía Prenatal , Neoplasias Uterinas/patología
9.
Ann Oncol ; 23(10): 2578-2584, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22492698

RESUMEN

BACKGROUND: Many easily measurable and readily available factors are now established as being prognostic in primary operable breast cancer. We here applied the 2011 St Gallen surrogate definition for breast cancer subclassification using tumor grade instead of Ki67. PATIENTS AND METHODS: Four thousand three hundred and eighteen consecutive patients who had surgery for primary operable breast cancer (1 January 2000 and 31 December 2009) in UZ Leuven excluding primary metastastic male breast cancers and those receiving neoadjuvant therapy. Five different surrogate phenotypes were created using the combined expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 together with tumor grade. Disease-free interval (DFI), distant metastastis-free interval (DMFI), locoregional relapse-free interval (LRRFI), breast cancer-specific survival (BCSS) and overall survival (OS) were calculated. RESULTS: Surrogate phenotypes present with significant differences in DFI, DMFI, LRRFI, BCSS and OS. 'Luminal A' tumors presented with the best outcome parameters but the effect weakened at longer follow-up. CONCLUSIONS: The four surrogate markers, agreed upon by the 2011 St Gallen consensus, defined five prognostic surrogate phenotypes in a large series of consecutively treated breast cancer patients. Their prognostic value changed with longer follow-up. The added value of gene expression profile over classical pathological assessment remains to be defined.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Hospitalización , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/metabolismo , Quimioterapia Adyuvante , Estudios de Cohortes , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Análisis de Supervivencia
10.
Eur J Gynaecol Oncol ; 32(4): 431-4, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21941970

RESUMEN

BACKGROUND: The development of cancer from adenomyotic foci is a rare occurrence. The diagnosis is frequently delayed because of the absence of tumor in the eutopic endometrium. CASE REPORT: We present a case of a 64-year-old postmenopausal woman with irregular vaginal bleeding and dull abdominal pain. Hysteroscopy was negative and hormonal treatment was continued. Nine months later, persisting symptoms necessitated endometrial biopsy revealing an atrophic endometrium. Hydrosonography suggested an endometrial polyp of 14 x 7 mm with a surrounding regular thin endometrium and a diffusely inhomogeneous ultrasonographic pattern throughout the myometrium. Hysteroscopic excision of the endometrial polyp was performed. Biopsies obtained during operative hysteroscopy showed a well differentiated endometrioid endometrial carcinoma. A laparoscopically assisted vaginal hysterectomy with bilateral salpingo-oophorectomy, pelvic lymphadenectomy and peritoneal cytology was performed. Pathologic examination revealed an atrophic endometrium and a Stage IB (FIGO 2009) well differentiated endometrioid endometrial carcinoma with prominent squamous differentiation originating from nodular adenomyosis. This ectopic localization of the endometrioid carcinoma added to a diagnostic delay of 12 months. CONCLUSION: Endometrial cancer arising from uterine adenomyosis may be difficult to diagnose. Awareness of this entity and careful ultrasonography are likely to reduce diagnostic delay.


Asunto(s)
Carcinoma Endometrioide/patología , Neoplasias Endometriales/patología , Endometriosis/patología , Neoplasias Primarias Secundarias/patología , Neoplasias Uterinas/patología , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/etiología , Diagnóstico Tardío , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/etiología , Endometriosis/complicaciones , Endometriosis/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/etiología , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/etiología
11.
Ultrasound Obstet Gynecol ; 38(1): 99-106, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21351179

RESUMEN

OBJECTIVES: To describe sonographic characteristics of malignant transformation in endometrioid cysts. METHODS: Women with a histological diagnosis of ovarian endometrioid cysts, borderline tumors arising in endometrioid cysts and carcinoma arising in endometrioid cysts, preoperatively examined sonographically, were included in this retrospective study. Gray-scale and Doppler ultrasound characteristics of the endometrioid cysts were compared with those of the borderline tumors and primary cancers arising in endometrioid cysts. The performance of an experienced examiner in classifying the masses was also assessed. RESULTS: Of 324 cases collected for the study, 309 (95.3%) lesions were classified as endometrioid cysts, four (1.2%) as borderline tumors arising in endometrioid cysts and 11 (3.4%) as carcinoma arising in endometrioid cysts. Women with malignant findings (borderline ovarian tumors and cancers) were older (median age 52 (range, 28-79) years) than those with benign endometrioid cysts (median age 34 (range, 18-76) years) (P<0.0001), and the prevalence of postmenopausal status was significantly higher in malignant cases. All (15/15) malignant tumors vs. 16% (50/309) of benign tumors were characterized by the presence of solid tissue (P<0.0001). The prevalence of solid tissue with positive Doppler signals was higher in malignant tumors (100%) than in benign cysts (7.8%) (P<0.0001). Papillary projections were a more frequent sonographic feature among malignant lesions (86.7%) than among benign endometrioid cysts (11.3%) (P<0.0001); power Doppler signals were detected within the projections in 92.3% and 37.1% of malignant and benign lesions, respectively. The examiner correctly diagnosed 94.8% (293/309) of benign lesions as benign and 93.3% (14/15) of malignant lesions as malignant. The risk estimation of the examiner was 'uncertain' in three (20%) and 'probably/certainly malignant' in 12 (80%) of 15 malignant cases. CONCLUSION: Borderline tumors and carcinomas arising in endometrioid cysts show a vascularized solid component at ultrasound examination.


Asunto(s)
Carcinoma Endometrioide/diagnóstico por imagen , Transformación Celular Neoplásica , Endometriosis/diagnóstico por imagen , Quistes Ováricos/diagnóstico por imagen , Neoplasias Ováricas/diagnóstico por imagen , Adolescente , Adulto , Anciano , Carcinoma Endometrioide/patología , Transformación Celular Neoplásica/patología , Endometriosis/complicaciones , Endometriosis/patología , Femenino , Humanos , Persona de Mediana Edad , Quistes Ováricos/patología , Neoplasias Ováricas/patología , Estudios Retrospectivos , Ultrasonografía Doppler en Color , Adulto Joven
12.
JBR-BTR ; 94(6): 330-2, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22338387

RESUMEN

Metastatic extramammary breast tumours are uncommon and differential diagnosis with primary breast carcinoma may prove to be difficult. We report a case of a metastasis of a renal cell cancer in the breast in a woman with a history of primary breast cancer. On follow-up of her breast carcinoma, a lump was detected via mammography and ultrasound. Core needle biopsy revealed a metastatic extramammary lesion originating from an asymptomatic renal cell carcinoma. We conclude that the diagnosis of metastasis to the breast from extramammary tumours is important to avoid unnecessary surgery and insure proper treatment of the primary disease.


Asunto(s)
Neoplasias de la Mama/secundario , Carcinoma de Células Renales/secundario , Neoplasias Renales/patología , Anciano de 80 o más Años , Biopsia , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/terapia , Carcinoma de Células Renales/diagnóstico , Diagnóstico por Imagen , Progresión de la Enfermedad , Femenino , Humanos
13.
Gynecol Obstet Invest ; 70(3): 186-91, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20558993

RESUMEN

A 50-year-old female complained of a painless abdominal distension. Histopathologic examination after cystectomy showed a primary poorly differentiated retroperitoneal mucinous cystadenocarcinoma with a sarcoma-like mural nodule. The patient subsequently underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, appendectomy, omentectomy and lymphadenectomy. Adjuvant chemotherapy consisted of 6 times carboplatin (AUC 7) in monotherapy (every 4 weeks). Based on 49 cases of primary retroperitoneal mucinous cystadenocarcinoma, we discuss the histogenesis and we define the appropriate treatment.


Asunto(s)
Cistadenocarcinoma Mucinoso/patología , Neoplasias Retroperitoneales/patología , Antineoplásicos/uso terapéutico , Apendicectomía , Carboplatino/uso terapéutico , Quimioterapia Adyuvante , Cistadenocarcinoma Mucinoso/tratamiento farmacológico , Cistadenocarcinoma Mucinoso/cirugía , Femenino , Humanos , Histerectomía , Escisión del Ganglio Linfático , Persona de Mediana Edad , Epiplón/cirugía , Ovariectomía , Pelvis/cirugía , Neoplasias Retroperitoneales/tratamiento farmacológico , Neoplasias Retroperitoneales/cirugía , Salpingectomía
14.
J Proteomics ; 73(8): 1454-60, 2010 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-20153848

RESUMEN

We present a novel approach to perform C-terminal sequence analysis by discriminating the C-terminal peptide in a mass spectral analysis of a CNBr digest. During CNBr cleavage, all Met-Xxx peptide bonds are cleaved and the generated internal peptides all end with a homoserine lactone (hsl)-derivative. The partial opening of the hsl-derivatives, by using a slightly basic buffer solution, results in the formation of m/z doublets (Deltam=18 Da) for all internal peptides and allows to identify the C-terminal peptide which appears as a singlet in the mass spectra. Using two model proteins we demonstrate that this approach can be applied to study proteins purified in gel or in solution. The chemical opening of the hsl-derivative does not require any sample clean-up and therefore, the sensitivity of the C-terminal sequencing approach is increased significantly. Finally, the new protocol was applied to characterize the C-terminal sequence of two recombinant proteins. Tandem mass spectrometry by MALDI-TOF/TOF allowed to identify the sequence of the C-terminal peptides. This novel approach will allow to perform a proteome-wide study of C-terminal proteolytic processing events in a high-throughput fashion.


Asunto(s)
Bromuro de Cianógeno , Fragmentos de Péptidos/química , Proteínas/química , Análisis de Secuencia de Proteína/métodos , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , Secuencia de Aminoácidos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos
15.
Patholog Res Int ; 2011: 918408, 2010 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-21253502

RESUMEN

Axillary lymph node involvement is an important prognostic factor for breast cancer survival but is confounded by the number of nodes examined. We compare the performance of the log odds prognostic index (Lpi), using a ratio of the positive versus negative lymph nodes, with the Nottingham Prognostic Index (NPI) for short-term breast cancer specific disease free survival. A total of 1818 operable breast cancer patients treated in the University Hospital of Leuven between 2000 and 2005 were included. The performance of the NPI and Lpi were compared on two levels: calibration and discrimination. The latter was evaluated using the concordance index (cindex), the number of patients in the extreme groups, and difference in event rates between these. The NPI had a significant higher cindex, but a significant lower percentage of patients in the extreme risk groups. After updating both indices, no significant differences between NPI and Lpi were noted.

16.
J Clin Pathol ; 62(7): 624-8, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19561231

RESUMEN

AIM: Basal-like breast tumours, as defined by microarrays, carry a poor prognosis and therapeutic options are limited to date. Often, these tumours are defined as oestrogen receptor (ER) negative/progesterone receptor (PR) negative/human epidermal growth factor receptor 2 (HER-2) negative (triple negative) by immunohistochemistry (IHC), but a more complete definition should include expression of basal cytokeratins (CK5/6, CK14 or CK17) and/or human epidermal growth factor receptor 1 (HER-1). The aim of this study was to investigate to what extent CK5/6 and HER-1 characterise the group of triple negative breast cancers. METHODS: Expression of CK5/6 and HER-1 was studied by IHC in 25 triple negative breast carcinomas and 32 grade-matched, non-triple-negative controls. All 57 cases were further subjected to fluorescence in situ hybridisation to investigate HER-1 gene copy number. RESULTS: CK5/6 and HER-1 expression was most frequent in triple negative tumours: 22 out of 25 cases (88.0%) expressed at least one of these markers (60.0% CK5/6 positive and 52.0% HER-1 positive). In the control group, CK5/6 and HER-1 expression was found in ER-negative but not in ER-positive tumours (ER negative/PR negative/HER-2 positive tumours: 20.0% CK5/6 positive and 46.7% HER-1 positive). HER-1 gene amplification was found in five cases only: four triple negative (16.0%) and one ER-negative control (ER negative/PR negative/HER-2 positive, 6.7%). Of interest, all five HER-1 amplified cases showed a remarkably homogeneous HER-1 expression pattern. CONCLUSION: Expression of CK5/6 and HER-1 is frequent in ER-negative breast cancers, in triple negative and in non-triple negative tumours. In a minority of cases, HER-1 overexpression may be caused by HER-1 gene amplification. Further studies are needed to investigate whether such cases might benefit from anti-HER-1 therapy.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias de la Mama/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Femenino , Amplificación de Genes , Humanos , Hibridación Fluorescente in Situ , Queratina-5/metabolismo , Queratina-6/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo
17.
Gynecol Obstet Invest ; 67(1): 46-8, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-18843183

RESUMEN

BACKGROUND: It is hypothesized that the HER-2/neu receptor could be used for targeted therapy in recurrent endometrial cancer. CASES: A patient with type II endometrial cancer (serous), showing strong HER-2/neu overexpression and gene amplification in both primary and recurrent tumor, received single-agent trastuzumab (3x weekly, 8 mg/kg loading, 6 mg/kg maintenance dose). Because of progression after 4 cycles, weekly paclitaxel-trastuzumab (80 mg/m(2) paclitaxel; trastuzumab 4 mg/kg loading, 2 mg/kg maintenance dose) was initiated. However, progressive disease was also noted after 11 weeks of combined treatment. A second patient, with recurrent type II endometrial cancer (grade III endometrioid), had HER-2/neu gene amplification in the primary tumor. However, biopsy from a lung metastasis 3 years later appeared to be HER-2/neu-negative. CONCLUSION: Based on lack of response and changes in tumor biology, trastuzumab was of little clinical value in 2 cases of recurrent type II endometrial cancer. This report underscores the importance of reassessment of a recurrent tumor before initiating targeted treatment.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma Endometrioide/tratamiento farmacológico , Neoplasias Endometriales/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales Humanizados , Carcinoma Endometrioide/enzimología , Neoplasias Endometriales/enzimología , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Recurrencia Local de Neoplasia/enzimología , Receptor ErbB-2/metabolismo , Trastuzumab
18.
Ultrasound Obstet Gynecol ; 31(4): 450-6, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18338427

RESUMEN

OBJECTIVES: To describe the clinical and ultrasound characteristics of granulosa cell tumors (GCTs) of the ovary, and to define the ultrasound appearance of GCTs based on pattern recognition. METHODS: Databases of four gynecological ultrasound centers were searched to identify patients with histologically proven GCTs who had undergone a standard preoperative ultrasound examination. RESULTS: A total of 23 women with confirmed GCT were identified. Twelve (52%) women were postmenopausal, nine (39%) were of fertile age and two (9%) were prepubertal. Clinical symptoms were abdominal distension (7/23, 30%), pain (5/23, 22%) and irregular vaginal bleeding (6/23, 26%). Seven patients (30%) were asymptomatic. Endometrial pathology was found in 54% (7/13) of the patients from whom endometrial biopsies were taken. On ultrasound scan 12/23 (52%) masses were multilocular-solid, 9/23 (39%) were purely solid, one mass (4%) was unilocular-solid and one mass was multilocular (4%). Multilocular and multilocular-solid cysts typically contained large numbers of small locules (> 10). The echogenicity of the cyst content was most often mixed (6/16, 38%) or low level (7/16, 44%). Papillary projections were found in only four women (17%). The GCTs were large tumors with a median largest diameter of 102 (range, 37-242) mm and manifested moderate or high color content at color Doppler examination (color score 3 in 13/23 tumors (57%); color score 4 in 8/23 tumors (35%)). CONCLUSIONS: At ultrasound examination, most GCTs are large multilocular-solid masses with a large number of locules, or solid tumors with heterogeneous echogenicity of the solid tissue. Hemorrhagic components are common and increased vascularity is demonstrated at color/power Doppler ultrasound examination. The hyperestrogenic state that is created by the tumor often causes endometrial pathology with bleeding problems as a typical associated symptom.


Asunto(s)
Tumor de Células de la Granulosa/diagnóstico por imagen , Ultrasonografía Doppler en Color/métodos , Neoplasias Uterinas/diagnóstico por imagen , Adolescente , Adulto , Anciano , Niño , Preescolar , Bases de Datos Factuales , Femenino , Tumor de Células de la Granulosa/complicaciones , Humanos , Menorragia/diagnóstico por imagen , Menorragia/etiología , Persona de Mediana Edad , Dolor/diagnóstico por imagen , Dolor/etiología , Estudios Retrospectivos , Hemorragia Uterina/diagnóstico por imagen , Hemorragia Uterina/etiología , Neoplasias Uterinas/complicaciones
19.
Br J Cancer ; 97(9): 1194-9, 2007 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-17895898

RESUMEN

The objective of this study is to assess the therapeutic importance of surgical castration, adjuvant hormonal treatment and lymphadenectomy in endometrial stromal sarcoma (ESS). A retrospective and multicentric search was performed. Clinicopathologic data were retrieved from cases that were confirmed to be ESS after central pathology review. The protocol was approved by the Ethical Committee. ESS was confirmed histopathologically in 34 women, but follow-up data were available in only 31 women. Surgical treatment (n=31) included hysterectomy with or without bilateral salpingo-oophorectomy (BSO) in 23 out of 31 (74%) and 8 out of 31 (26%) cases, respectively. Debulking surgery was performed in 6 out of 31 cases (19%). Stage distribution was as follows: 22 stage I, 4 stage III and 5 stage IV. Women with stage I disease recurred in 4 out of 22 (18%) cases. Among stage I women undergoing hormonal treatment with or without BSO, 3 out of 15 (20%) and 1 out of 7 (14%) relapsed, respectively. Among stages III-IV women receiving adjuvant hormonal treatment or not, 1 out of 5 (20%) and 3 out of 4 (75%) relapsed, respectively (differences=55.0%, 95% CI=-6.8-81.2%). Kaplan-Meier curves show comparable recurrence rates for stage I disease without adjuvant hormonal treatment when compared to stages III-IV disease treated with surgery and adjuvant hormonal treatment. Furthermore, women taking hormones at diagnosis have a better outcome when compared to women not taking hormonal treatment. Three out of 31 (9%) patients had a systematic lymphadenectomy whereas 3 out of 31 (9%) had a lymph node sampling. In one case, obvious nodal disease was encountered at presentation. Isolated retroperitoneal recurrence occurred in 1 out of 31 (3%) of all cases and in 1 out of 8 (13%) recurrences. This single woman later also developed lung and abdominal metastases. Leaving lymph nodes in situ does not appear to alter the clinical outcome of ESS. Although numbers are low, the retrospective data suggest that the need for surgical castration (BSO) in premenopausal women with early-stage disease should be discussed with the patient on an individual basis. The data support the current practice in some centres to administer adjuvant hormonal treatment.


Asunto(s)
Neoplasias Endometriales/terapia , Histerectomía , Escisión del Ganglio Linfático , Medroxiprogesterona/uso terapéutico , Sarcoma Estromático Endometrial/terapia , Adolescente , Adulto , Quimioterapia Adyuvante , Terapia Combinada , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Estadificación de Neoplasias , Estudios Retrospectivos , Sarcoma Estromático Endometrial/tratamiento farmacológico , Sarcoma Estromático Endometrial/cirugía , Resultado del Tratamiento
20.
Acta Clin Belg ; 62(3): 187-90, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17672184

RESUMEN

Non-Hodgkin's lymphoma (NHL) is a common cause of Fever of Unknown Origin (FUO) but the presentation as a gynaecologic malignancy is exceedingly rare. To our knowledge, this represents the first report of an intravascular large B-cell lymphoma of the uterus presenting with fever of unknown origin. After a standard clinical work-up for FUO, the endometrial curettage directed by the finding of a localized fluoro-deoxyglucose Positron Emission Tomography (FDG-PET) hot spot in the pelvic area, yielded material revealing an intr avascular B-cell lymphoma. A total abdominal hysterectomy confirmed the presence of an intravascular large B-cell lymphoma in the lumina of small blood vessels of the uterus.


Asunto(s)
Fiebre de Origen Desconocido/etiología , Linfoma de Células B/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Tomografía de Emisión de Positrones , Neoplasias Uterinas/diagnóstico por imagen , Útero/irrigación sanguínea , Neoplasias Vasculares/diagnóstico por imagen , Resultado Fatal , Femenino , Humanos , Inmunohistoquímica , Linfoma de Células B/complicaciones , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/metabolismo , Persona de Mediana Edad , Neoplasias Uterinas/complicaciones , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/metabolismo , Neoplasias Vasculares/complicaciones
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