RESUMEN
Mixed endometrial carcinomas are defined as a combination of 2 or more distinct histologic subtypes, one of which must be a type II tumor comprising at least 5% of the tumor volume. The oncogenesis of these tumors remains unclear, particularly in light of the increasingly appreciated morphologic overlap among subtypes, as well as evolving molecular data. We evaluated 8 cases of mixed endometrial carcinoma, including 4 endometrioid (EC)/serous (SC), 1 SC/clear cell (CC), and 3 EC/CC cases, to study the underlying molecular features and oncogenic mechanisms at play. Each component was analyzed by a targeted next-generation sequencing assay. All tumors shared mutations in both components. In 6 cases, one component showed additional mutations. Two EC/SC cases showed shared mutations and mutations unique to each component. When present, unique mutations were typically seen in the SC component, including variants in POLE and TP53, as well as potentially targetable genes DDR2, MAP2K1, and CCNE1. In EC/SC tumors, ERBB2 abnormalities were seen in 2 cases. EC/CC cases showed FGFR2 activating mutations in the EC component only. No fusion drivers were identified. Our data suggest that the majority of these tumors begin as a single clone and diverge along 2 pathways: (1) tumor progression, with one component showing additional mutations, and (2) tumor divergence, in which tumor components have both shared mutations and mutations unique to each component. In addition, the findings suggest a component of morphologic mimicry in these tumors. Our findings are clinically relevant since targetable mutations may be present in only one component of mixed tumors.
Asunto(s)
Adenocarcinoma de Células Claras/genética , Biomarcadores de Tumor/genética , Carcinoma Endometrioide/genética , Neoplasias Endometriales/genética , Mutación , Neoplasias Complejas y Mixtas/genética , Neoplasias Quísticas, Mucinosas y Serosas/genética , Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/patología , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Carcinoma Endometrioide/química , Carcinoma Endometrioide/patología , Neoplasias Endometriales/química , Neoplasias Endometriales/patología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Neoplasias Complejas y Mixtas/química , Neoplasias Complejas y Mixtas/patología , Neoplasias Quísticas, Mucinosas y Serosas/química , Neoplasias Quísticas, Mucinosas y Serosas/patología , FenotipoRESUMEN
Objective: To study the pathologic features of fallopian tubal epithelium in patients with pelvic high-grade serous carcinoma (HGSC), to investigate its role in pelvic serous carcinogenesis and to reclassify the primary site of HGSC based on recently proposed criteria. Methods: The fallopian tubes in 58 cases of pelvic HGSC (54 cases of ovarian primary, 3 cases of tubal primary, 1 case of peritoneum) and 25 cases of pelvic non-HGSC (5 cases of ovarian low-grade serous cancer, 9 cases of endometrioid cancer, and 11 cases of clear cell ovary carcinoma) were collected from June 2015 to December 2016, and serially examined under light microscope (SEE-FIM protocol). Immunostaining for p53 and Ki-67 was performed to evaluate the presence of p53 signature, serous tubal intraepithelial lesion (STIL), serous tubal intraepithelial carcinoma (STIC) and invasive carcinoma in these fallopian tubes. Meanwhile, primary site of HGSC based on the recently proposed diagnostic criteria were also reclassified. Results: Among the study group, the frequencies of p53 signature, STIL, STIC and invasive HGSC were 27.6% (16/58), 43.1% (25/58), 36.2% (21/58) and 67.2% (39/58), respectively, while in control group, the proportions were 24.0% (6/25), 0, 0 and 8.0% (2/25), respectively. The continuum of epithelial changes in the process of serous neoplasia including p53 signature, STIL, STIC and invasive carcinoma was identified in 8 cases of pelvic HGSC. The proportions of STIL, STIC and invasive carcinomas in HGSC group were higher than that in non-HGSC group (P<0.01). About 80.0% (20/25) of STIL and 85.7% (18/21) of STIC were present unilaterally. Diagnostically, the study group contained the 17 cases of ovarian HGSC, 40 cases of tubal HGSC, and 1 case of peritoneal HGSC after reclassification of the cancer primary. Conclusions: Continuous changes of tubal epithelium including p53 signature, STIL, STIC and invasive carcinomas are identified in patients with HGSC, supporting the current understanding that the fallopian tube is likely the cellular source of the majority HGSC. STIL and STIC may be specific to pelvic HGSC and may act as a target for future research on the early detection and prevention of this disease. The newly proposed diagnostic criteria for pelvic HGSC will lead us to more accurate classification of cancer primary sites. Correct classification of HGSC may have potential impacts for cancer prevention and improve our understanding of ovarian serous carcinogenesis.
Asunto(s)
Carcinoma Endometrioide/patología , Epitelio/patología , Neoplasias de las Trompas Uterinas/patología , Trompas Uterinas/patología , Neoplasias Ováricas/patología , Adenocarcinoma in Situ/química , Adenocarcinoma in Situ/patología , Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/patología , Carcinogénesis , Carcinoma Endometrioide/química , Cistadenocarcinoma Seroso/química , Cistadenocarcinoma Seroso/patología , Epitelio/química , Neoplasias de las Trompas Uterinas/química , Trompas Uterinas/química , Femenino , Humanos , Antígeno Ki-67/análisis , Neoplasias Ováricas/química , Proteína p53 Supresora de Tumor/análisisRESUMEN
OBJECTIVE: Ovarian clear cell carcinoma (OCCC) frequently presents at an early stage. In stage I OCCC, the prognosis differs according to substage. In particular, predictive biomarkers and new treatment strategies are needed for stage IC2/IC3 disease. We investigated tumor biology and prognostic factors for stage I OCCC from a clinicopathological perspective, including the expression of ARID1A and IL-6, which are considered critical for OCCC carcinogenesis. METHODS: A retrospective cohort study of 192 patients with stage I OCCC treated at a single institution was performed. We calculated overall survival (OS) with respect to 12 clinicopathological parameters that included the unique and diverse histological features of OCCC. RESULTS: The estimated 5-year OS rate in patients with all stage I OCCC was 88.9% during a median of 91months of follow-up. The multivariate analysis indicated that substage classification and IL-6 expression status were associated with poor OS (p=0.010 and p=0.027, respectively). Loss of ARID1A expression had no impact on survival; however, it was associated with substage (p=0.001), capsule rupture status (p=0.011), and ascites cytology (p=0.016). No clear association was found between ARID1A and IL-6 expressions. Histological findings, including the presence of endometriosis, adenofibroma, architectural pattern, and tumor cell type, showed no prognostic effects. CONCLUSIONS: Both substage classification and IL-6 expression status may be independent prognostic factors in stage I OCCC. Therefore, IL-6 molecular stratification may be crucial in optimizing therapeutic strategies for early stage OCCC to improve survival.
Asunto(s)
Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/patología , Interleucina-6/análisis , Neoplasias Ováricas/química , Neoplasias Ováricas/patología , Adenocarcinoma de Células Claras/terapia , Adulto , Anciano , Anciano de 80 o más Años , Ascitis/patología , Biomarcadores de Tumor/análisis , Proteínas de Unión al ADN , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Proteínas Nucleares/análisis , Neoplasias Ováricas/terapia , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Transcripción/análisisRESUMEN
OBJECTIVE: Our aim was to study the expression of L1CAM in endometrioid and clear cell ovarian carcinomas and to evaluate its correlation with clinical parameters and patient prognosis. METHODS: Tissue microarray -based immunohistochemical analysis of L1CAM expression was performed in 249 endometrioid and 140 clear cell ovarian carcinomas. Concurrent endometrial carcinoma was found in 57 of these patients. RESULTS: L1CAM expression was found in 15% of endometrioid and 23% of clear cell ovarian carcinomas. L1CAM expression was strongly associated with poor disease-specific overall survival and poor disease-free survival in endometrioid (p<0.0001, p=0.0005), but not in clear cell ovarian carcinomas. Significant association of L1CAM expression with poor overall survival was observed in grade 1-2 carcinomas (p<0.0001), but not in grade 3 tumors. In endometrioid ovarian carcinomas, L1CAM expression was associated with aggressive tumor characteristics, such as higher grade and stage, and incomplete response to primary therapy. However, L1CAM expression was not an independent prognostic factor for overall or disease-free survival. Of the 57 patients with concurrent endometrial carcinoma L1CAM positivity was found in 4 cases both in the ovarian and endometrial tumors, and in 3 cases only in the endometrial tumor. All these seven patients with L1CAM positive tumors had poor outcome. CONCLUSIONS: L1CAM expression could serve as a biomarker for predicting clinical outcome and response to therapy in patients with endometrioid ovarian carcinoma, but not in clear cell carcinomas. L1CAM positivity also predicts poor outcome in patients with concurrent endometrioid ovarian and endometrial carcinomas.
Asunto(s)
Adenocarcinoma de Células Claras/química , Carcinoma Endometrioide/química , Neoplasias Endometriales/química , Neoplasias Primarias Múltiples/química , Molécula L1 de Adhesión de Célula Nerviosa/análisis , Neoplasias Ováricas/química , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/terapia , Biomarcadores de Tumor/análisis , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/terapia , Supervivencia sin Enfermedad , Neoplasias Endometriales/patología , Neoplasias Endometriales/terapia , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/terapia , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The presence of trophoblastic differentiation or nongestational choriocarcinoma in a carcinoma is rare but has been described in various organs, including in the female genital tract. We report a cervical clear cell carcinoma admixed with a component of choriocarcinoma in a 52-year-old woman, only the second report of this combination in the literature. Immunohistochemically, the tumor exhibited isolated loss of staining with the mismatch repair protein MSH6. We review the literature on trophoblastic differentiation in cervical carcinoma.
Asunto(s)
Adenocarcinoma de Células Claras/patología , Coriocarcinoma/patología , Proteínas de Unión al ADN/análisis , Neoplasias del Cuello Uterino/patología , Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/cirugía , Diferenciación Celular , Coriocarcinoma/química , Coriocarcinoma/cirugía , Reparación de la Incompatibilidad de ADN , Proteínas de Unión al ADN/deficiencia , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Trofoblastos/patología , Neoplasias del Cuello Uterino/química , Neoplasias del Cuello Uterino/cirugía , Útero/patologíaRESUMEN
Endometrial carcinoma (EC) is traditionally characterized as endometrioid and nonendometrioid based on histopathologic phenotypes. Molecular-based classifications have been proposed, but are not widely implemented. Herein we examine molecular profiles between EC histologic subtypes. 3133 ECs were submitted between March 2011 and July 2014: 1634 Type I and 1226 Type II. In situ hybridization and immunohistochemistry were used to assess copy number and protein expression of selected genes. Sequenced variants in 47 genes were analyzed using the Illumina TruSeq Amplicon Cancer Panel. Type II EC included 628 cases of uterine serous cancer (USC), 136 cases of clear cell (CC), 361 cases of carcinosarcoma (CS), 38 cases of mucinous, and 36 cases of squamous cell. PI3K/Akt/mTOR pathway was most frequently dysregulated within Type I and mucinous histologies, least altered in CS and squamous. PD-L1 expression was highest in mucinous, absent in squamous. ER/PR expression was common in Type II, most frequent in USC, mucinous, and squamous. Receptor tyrosine kinase was frequently dysregulated in Type II disease: HER2 amplification highest in USC and CC, EGFR mutations exclusively seen in mucinous EC, KRAS mutations common in mucinous, squamous, and Type I, and c-MET overexpression high in CC and mucinous. BRCA1 and BRCA2 were most frequently mutated in CS. Grade 3 EC shares features of G1 tumor and Type II disease, most notably resembling CS. Endometrial carcinomas are a molecularly heterogeneous group of tumors. A histology-based molecular map can identify rational targets to optimize treatment and guide future clinical trials.
Asunto(s)
Carcinoma Endometrioide/patología , Neoplasias Endometriales/patología , Proteínas de Neoplasias/análisis , Transcriptoma , Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/secundario , Adenocarcinoma Mucinoso/química , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/secundario , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/química , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/secundario , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/secundario , Carcinosarcoma/química , Carcinosarcoma/patología , Carcinosarcoma/secundario , Reparación del ADN/genética , ADN de Neoplasias/genética , Neoplasias Endometriales/química , Neoplasias Endometriales/genética , Neoplasias Endometriales/secundario , Femenino , Dosificación de Gen , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Transducción de Señal/efectos de los fármacos , Adulto JovenRESUMEN
A 48-year-old woman had a left breast mass identified during routine breast cancer screening. The mammogram showed pleomorphic-segmental microcalcifications in the mediolateral-oblique view of the left breast. Ultrasonography showed a hypoechoic mass approximately 3.7 cm in diameter with multiple calcifications. Contrast-enhanced magnetic resonance imaging of the breast showed non-mass like enhancement of approximately 4 cm in diameter in the C area of the left breast. She was diagnosed with glycogen-rich clear cell carcinoma (GRCC) by ultrasound-guided vacuum-assisted biopsy. Nipplesparing mastectomy was performed along with sentinel lymph node biopsy. The intraoperative consultation suggested sentinel lymph node metastasis and we therefore performed axillary lymph node dissection. Pathological examination reported microinvasive carcinomas, 0.4 cm in maximum diameter, and extensive intraductal components, 5 cm in size. The tumor cells were stained on PAS staining, but the stains were digested with diastase. The cells were negative for adipophilin. GRCC was first reported by Hull et al. This is a rare type of breast carcinoma. There is no standard therapy for this disease or any data on the prognosis of breast cancer patients with GRCC.
Asunto(s)
Adenocarcinoma de Células Claras , Neoplasias de la Mama/patología , Ganglios Linfáticos/patología , Micrometástasis de Neoplasia , Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/cirugía , Axila/patología , Neoplasias de la Mama/química , Neoplasias de la Mama/cirugía , Femenino , Glucógeno/análisis , Humanos , Mastectomía , Persona de Mediana Edad , Pronóstico , Biopsia del Ganglio Linfático CentinelaRESUMEN
OBJECTIVE: The S100P protein stimulates cell proliferation and survival, thereby contributing to cancer progression. The purposes of this study were to evaluate S100P expression in ovarian clear cell adenocarcinoma and to determine whether S100P expression was correlated with the clinicopathological features or prognoses of patients with clear cell adenocarcinoma. METHODS: We examined S100P expression in 30 ovarian clear cell adenocarcinoma specimens using immunohistochemistry analysis. The Kaplan-Meier method was used for analysis of overall survival, and comparisons were made based on the log-rank test. RESULTS: Negative staining for nuclear S100P was associated with a poor prognosis as compared with that of positive staining for nuclear S100P in specimens from patients with clear cell adenocarcinoma. CONCLUSIONS: These data suggested that S100P may serve as an independent prognostic factor and marker for acquired resistance to chemotherapeutic drugs in clear cell adenocarcinoma.
Asunto(s)
Adenocarcinoma de Células Claras/química , Proteínas de Unión al Calcio/análisis , Proteínas de Neoplasias/análisis , Neoplasias Ováricas/química , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Pronóstico , Tasa de SupervivenciaRESUMEN
OBJECTIVE: Upregulation of cyclin E and cyclin D1-6 accelerates the transition from G1 to S phase. The objective of this study was to determine if cyclin D1 and E are prognostic indicators in endometrial cancer. MATERIALS AND METHODS: Surgically-treated patients with endometrial carcinoma had their tumors stained for nuclear expression of cyclin D1 and E. Quantification of staining and measurement of growth phase fraction were performed using image analysis. FIGO stage, grade, and histology were also analyzed. RESULTS: Cyclin D1 and E expression was unrelated to DNA index (p = 0.93). While cyclin D1 expression did not correlate with S+G2M phase fraction (p = 0.69), increased cyclin E expression was directly correlated with increased S+G2M phase fraction (p = 0.002). Cyclin E expression was highest in clear cell carcinomas (p = 0.042) while cyclin D1 expression was highest in adenosquamous carcinomas (p = 0.028). Patients dying from cancer had significantly higher expression of cyclin D1 (p = 0.042) and E (p = 0.02) as compared to patients surviving their disease. Multivariate logistic regression revealed FIGO stage, grade, and lack of cyclin E overexpression to be independent prognostic indicators of survival. CONCLUSION: Cyclin E expression is related to increased growth fraction, clear cell histology, and decreased survival in patients with endometrial cancer.
Asunto(s)
Adenocarcinoma de Células Claras/mortalidad , Ciclina E/análisis , Neoplasias Endometriales/mortalidad , Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/patología , Ciclina D1/análisis , Neoplasias Endometriales/química , Neoplasias Endometriales/patología , Femenino , Humanos , Modelos Logísticos , Estadificación de Neoplasias , PronósticoRESUMEN
Hepatocyte nuclear factor-1ß (HNF-1ß) is a transcriptional factor that has an important role in endometriosis-ovarian clear cell carcinoma (OCCC) sequence by modulating cell kinetics and glucose metabolism. However, little is known about the detailed molecular mechanisms that govern its regulation and function. Herein, we focus on upstream and downstream regulatory factors of HNF-1ß in OCCCs. In clinical samples, HNF-1ß expression was positively correlated with the active form of NF-κB/p65 in OCCCs, and closely linked with a low nuclear grade and non-solid architecture. In cell lines, transfection of p65 resulted in increased HNF-1ß mRNA and protein expression in TOV-21G cells (OCCC cell line with endogenous HNF-1ß expression), in line with activation of the promoter, probably through interacting with the basic transcriptional machinery. Suppression of endogenous HNF-1ß expression by siRNA increased apoptosis in TOV-21G cells, while treatment of Hec251 cells (endometrial carcinoma cell line with extremely low endogenous HNF-1ß expression) stably overexpressing exogenous HNF-1ß with doxorubicin abrogated apoptosis of the cells, along with increased ratio of bcl-2 relative to bax. Moreover, overexpression of HNF-1ß led to upregulation of bcl-2 expression at the transcriptional level in TOV-21G cells, which provided evidence for a positive correlation between HNF-1ß and bcl-2 expression in OCCCs. These data, therefore, suggest that association between HNF-1ß and NF-κB signaling may participate in cell survival by alteration of apoptotic events, particularly in mitochondria-mediated pathways, through upregulation of bcl-2 expression in OCCCs.
Asunto(s)
Adenocarcinoma de Células Claras/metabolismo , Apoptosis/genética , Factor Nuclear 1-beta del Hepatocito/genética , FN-kappa B/genética , Neoplasias Ováricas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/patología , Adulto , Anciano , Proliferación Celular/genética , Femenino , Factor Nuclear 1-beta del Hepatocito/metabolismo , Humanos , Inmunohistoquímica , Persona de Mediana Edad , FN-kappa B/metabolismo , Quistes Ováricos/química , Quistes Ováricos/metabolismo , Quistes Ováricos/patología , Neoplasias Ováricas/química , Neoplasias Ováricas/patología , Ovario/química , Ovario/metabolismo , Ovario/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
Clear cell thymic carcinoma is a rare and invasive tumor of the mediastinum for which there are no uniform treatment guidelines. The combination of carboplatin plus paclitaxel seems to be the most effective regimen for this disease. We report a case of locally advanced clear cell thymic carcinoma treated with this schedule, in which we observed a relevant and rapid tumor shrinkage.
Asunto(s)
Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Terapia Neoadyuvante/métodos , Neumonectomía , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/terapia , Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/tratamiento farmacológico , Adenocarcinoma de Células Claras/cirugía , Adulto , Carboplatino/administración & dosificación , Quimioterapia Adyuvante , Humanos , Biopsia Guiada por Imagen/métodos , Inmunohistoquímica , Masculino , Paclitaxel/administración & dosificación , Derrame Pericárdico/etiología , Derrame Pleural/etiología , Neumonectomía/métodos , Radioterapia Adyuvante , Toracotomía , Neoplasias del Timo/química , Neoplasias del Timo/tratamiento farmacológico , Neoplasias del Timo/cirugía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Hyalinizing clear cell carcinoma (HCCC) has only been described in salivary glands of the head and neck. We report a 38-year-old man with a 2.6-cm lung tumor that was growing in a peribronchial location and had morphologic features of HCCC. The tumor cells expressed cytokeratin 7 and keratin AE1/AE3, and the vast majority of tumor cells marked also with p63 and p40. They were negative for cytokeratin 20, S-100, smooth muscle actin, napsin A, and thyroid transcription factor-1. Fluorescence in situ hybridization revealed Ewing Sarcoma Breakpoint Region 1 (EWSR1) rearrangement, and reverse-transcription polymerase chain reaction confirmed the presence of the EWSR1-Activating Transcription Factor 1 (ATF1) fusion transcript, which was subsequently sequenced. The morphologic, immunophenotypic, cytogenetic, and molecular findings together with the patient's history and location of the tumor support a diagnosis of primary pulmonary HCCC of bronchial submucosal gland origin. It is our understanding that this is the first report of HCCC arising as a primary tumor outside the head and neck region.
Asunto(s)
Adenocarcinoma de Células Claras/patología , Carcinoma Broncogénico/patología , Neoplasias Pulmonares/patología , Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/genética , Adulto , Proteínas de Unión a Calmodulina/química , Proteínas de Unión a Calmodulina/genética , Carcinoma Broncogénico/química , Carcinoma Broncogénico/genética , Reordenamiento Génico , Humanos , Epítopos Inmunodominantes/análisis , Inmunohistoquímica , Queratina-7/análisis , Queratinas Específicas del Pelo/análisis , Neoplasias Pulmonares/química , Neoplasias Pulmonares/genética , Masculino , Proteínas de la Membrana/análisis , Fragmentos de Péptidos/análisis , Proteína EWS de Unión a ARN , Proteínas de Unión al ARN/química , Proteínas de Unión al ARN/genéticaAsunto(s)
Adenocarcinoma de Células Claras/patología , Neoplasias de la Vesícula Biliar/patología , Vesícula Biliar/patología , Pólipos/patología , Enfermedad Aguda , Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/clasificación , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/epidemiología , Adenocarcinoma de Células Claras/cirugía , Anciano de 80 o más Años , Biomarcadores de Tumor , Colecistectomía , Colelitiasis/complicaciones , Diagnóstico Diferencial , Femenino , Neoplasias de la Vesícula Biliar/química , Neoplasias de la Vesícula Biliar/diagnóstico , Neoplasias de la Vesícula Biliar/epidemiología , Neoplasias de la Vesícula Biliar/cirugía , Glipicanos/análisis , Humanos , Técnicas para Inmunoenzimas , Incidencia , Absceso Hepático/complicaciones , Músculo Liso/patología , Estadificación de Neoplasias , Pancreatitis/complicaciones , Pancreatitis/etiología , Reacción del Ácido Peryódico de Schiff , Pólipos/química , Pólipos/diagnóstico , Pólipos/cirugía , Factores de RiesgoAsunto(s)
Adenocarcinoma de Células Claras/diagnóstico , Biomarcadores de Tumor/análisis , Neoplasias Ováricas/diagnóstico , Conductos Mesonéfricos/patología , Adenocarcinoma de Células Claras/química , Adulto , Anciano , Cistadenocarcinoma Seroso/diagnóstico , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/química , Pronóstico , Enfermedades Raras/diagnóstico , Receptores de Estrógenos/análisis , Sistema de Registros , Estudios Retrospectivos , Federación de Rusia/epidemiología , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/análisisRESUMEN
Epithelial ovarian cancer (EOC) is often asymptomatic and thus diagnosed at advanced stages with a poor prognosis. False-negative results for the conventional marker CA125 frequently occur in cases of clear cell carcinoma (CCC), a type of EOC; therefore, it is necessary to develop biomarkers with greater sensitivity. We previously reported a strategy to discover glycobiomarker candidates by combined lectin microarray and IGOT-LC/MS analysis. We have now optimized this strategy for discovering EOC biomarkers. Glycopeptides possessing cancerous glycans were enriched from the ascites fluids and culture supernatants of cancer cell lines with a fucose-binding lectin, AAL. IGOT-LC/MS analysis of CCC samples yielded 144 candidate glycoproteins. We selected WFA by lectin microarray as the optimal lectin to distinguish EOC from gastric and colon cancer. The candidates were narrowed by Western analysis of the WFA-bound fraction of ascites fluids. One of the final candidates, WFA-reactive ceruloplasmin, produced higher signals in the ascites fluids of EOC patients, including CCC, in comparison with the benign samples, while CA125 levels were comparable in the sandwich ELISA. Thus, our glycoproteomic strategy featuring efficient enrichment of glycans with disease-related alterations is applicable to various diseases.
Asunto(s)
Adenocarcinoma de Células Claras/química , Biomarcadores de Tumor/análisis , Ceruloplasmina/análisis , Glicoproteínas/análisis , Neoplasias Glandulares y Epiteliales/química , Neoplasias Ováricas/química , Adenocarcinoma de Células Claras/diagnóstico , Líquido Ascítico/química , Antígeno Ca-125/análisis , Carcinoma Epitelial de Ovario , Ceruloplasmina/química , Cromatografía Liquida , Femenino , Humanos , Espectrometría de Masas , Neoplasias Glandulares y Epiteliales/diagnóstico , Neoplasias Ováricas/diagnóstico , Lectinas de Plantas/química , Polisacáridos/análisis , Polisacáridos/química , Análisis por Matrices de Proteínas , Receptores N-Acetilglucosamina/químicaRESUMEN
A case of recurrent hyalinizing clear cell carcinoma (HCCC) of the parotid gland in a 46-year-old female is here introduced. The patient had undergone a left superficial parotidectomy 6 months ago in another institution for an alleged benign, circumscribed mass 2.4 cm in diameter of the left parotid gland. Histopathological examination revealed a poorly differentiated HCCC bearing a EWSR-1 translocation on FISH examination. Fine Needle Cytology (FNC) was performed on three separate soft tissue masses in the pre-masseterine area and a cytological diagnosis of recurrent, poorly differentiated, possibly aggressive variant of HCCC, was rendered. FISH performed on a destained Diff Quik stained smear demonstrated an ESWR-1 translocation, which supported the cytopathological diagnosis. The cytomorphologic features and the differential diagnosis of this aggressive variant of HCCC are briefly discussed.
Asunto(s)
Adenocarcinoma de Células Claras/patología , Recurrencia Local de Neoplasia/patología , Neoplasias de la Parótida/patología , Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/diagnóstico por imagen , Biomarcadores de Tumor/análisis , Biopsia con Aguja Fina , Femenino , Humanos , Queratinas/análisis , Persona de Mediana Edad , Neoplasias de la Parótida/química , Neoplasias de la Parótida/diagnóstico por imagen , Enfermedades Raras , UltrasonografíaAsunto(s)
Adenocarcinoma de Células Claras/patología , Glucógeno/análisis , Neoplasias Gástricas/patología , Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/clasificación , Adenocarcinoma de Células Claras/cirugía , Anciano , Biopsia , Diferenciación Celular , Gastrectomía , Humanos , Masculino , Coloración y Etiquetado , Neoplasias Gástricas/química , Neoplasias Gástricas/cirugíaRESUMEN
BACKGROUND: The microenvironmental biomarkers of different subtypes of ovarian cancers arising from endometriosis have not been studied in Taiwan. Their expression can help in understanding the carcinogenic mechanism. METHODS: Our study used immunohistochemistry to compare the expression of estrogen receptor (ER), hepatocyte nuclear factor-1 beta (HNF1ß), p53, phosphatase and tensin homolog (PTEN), BAF250a, and cyclooxygenase-2 (COX-2) among 79 cases of endometriosis-associated ovarian cancers, including 40 (50%) clear cell carcinomas (CCCs), 33 (41%) endometrioid (EM) adenocarcinomas, four (5%) serous carcinomas, one adenosquamous carcinoma, and one adenosarcoma. RESULTS: Positive stainings for ER, HNF1ß, p53, and COX-2 were identified in 34 (43%), 30 (38%), 10 (13%), and 44 (56%) cases. Loss of PTEN and BAF250a were noted in 29 (37%) and 37 (47%) cases. The expression of ER was reversely correlated with that of HNF1ß (rho = -0.417, p < 0.001) and correlated with p53 (rho = 0.284, p = 0.011). ER positivity was commonly identified in EM adenocarcinomas (91%), and rarely in CCCs (8%) and serous carcinoma (0%; p < 0.001). By contrast, HNF1ß expression was frequently noted in CCCs (65%) and serous carcinomas (50%), but less in EM adenocarcinoma (6%; p < 0.001). All staining results were similar between atypical endometriosis glandular epithelium and contiguous malignant parts. Only nine cases showed 10 minor differences (10/474, 2%) in ER, HNF1ß, and BAF250a. For the staining patterns of p53, COX-2, and PTEN, there was no difference between the invasive and precursor parts. CONCLUSION: Our results supported the suggestion that estrogen-dependent ovarian cancer arising from endometriosis is substantially more associated with EM adenocarcinoma than CCCs. The positive HNF1ß staining was a frequent finding in CCCs, but not in EM adenocarcinoma. The similar staining patterns of atypical endometriosis glandular cells with the invasive parts confirmed their precursor status.
Asunto(s)
Biomarcadores de Tumor/análisis , Endometriosis/complicaciones , Neoplasias Ováricas/química , Microambiente Tumoral/fisiología , Adenocarcinoma/química , Adenocarcinoma de Células Claras/química , Ciclooxigenasa 2/análisis , Proteínas de Unión al ADN , Endometriosis/patología , Femenino , Factor Nuclear 1-beta del Hepatocito/análisis , Humanos , Neoplasias Hormono-Dependientes/química , Proteínas Nucleares/análisis , Neoplasias Ováricas/etiología , Neoplasias Ováricas/patología , Fosfohidrolasa PTEN/análisis , Receptores de Estrógenos/análisis , Factores de Transcripción/análisis , Proteína p53 Supresora de Tumor/análisisRESUMEN
PURPOSE: Alteration of CyclinD1 was suggested to relate with development of endometrial carcinogenesis before, however CyclinD1 expression is not well defined in endometrial hyperplasia lesions. We checked the relationship between its expression and clinic-pathological variables of endometrial lesions to explore the possibility for CyclinD1 as a potential diagnostic and prognostic marker. METHODS: Cyclin D1 immunohistochemical analysis (IHC) was used to evaluate 201 fixed, paraffin-embedded endometrial samples which included simple hyperplasia (n = 27), atypical complex hyperplasia (ACH) (n = 41), endometrioid carcinoma (n = 103), endometrial serous carcinoma (ESC) (n = 21) and clear cell carcinoma (CCC) (n = 9). A breast cancer with known CyclinD1 expression was selected as a positive control in each immunohistochemistry run. We also performed follow-up study to estimate patients' prognosis. RESULTS: CyclinD1 was significantly overexpressed in atypical complex hyperplasia (ACH), endometrioid carcinoma and clear cell carcinoma (CCC). The positive signaling of CyclinD1 was showed less than 40% in simple hyperplasia and endometrial serous carcinoma (ESC). The high expression of CyclinD1 was observed in metastasis carcinoma group more significantly than non-metastasis carcinoma group. Kaplan Meier analysis demonstrated that patients with high CyclinD1 expression had an obviously poor prognosis than patients without CyclinD1 staining (p < 0.05). Moreover, according to multivariate Cox regression analysis, CyclinD1 expression, as crucial as metastasis, was a risk marker for overall survival rate. CONCLUSION: CyclinD1 exhibited a promising potential to predict the prognosis of patients with endometrial carcinoma. However, the statistical analysis demonstrated that CyclinD1 exhibited a poor ability to differentiate neoplastic lesions from non-neoplastic lesions; thus, the application of CyclinD1 only is not so credible for differentiation between benign and malignant lesions. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1871063048950173.
Asunto(s)
Adenocarcinoma de Células Claras/química , Biomarcadores de Tumor/análisis , Carcinoma Endometrioide/química , Ciclina D1/análisis , Hiperplasia Endometrial/metabolismo , Neoplasias Endometriales/química , Endometrio/química , Neoplasias Quísticas, Mucinosas y Serosas/química , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/secundario , Adulto , Biopsia , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/secundario , Distribución de Chi-Cuadrado , Hiperplasia Endometrial/mortalidad , Hiperplasia Endometrial/patología , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Endometrio/patología , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Persona de Mediana Edad , Análisis Multivariante , Neoplasias Quísticas, Mucinosas y Serosas/mortalidad , Neoplasias Quísticas, Mucinosas y Serosas/secundario , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Factores de Tiempo , Regulación hacia ArribaRESUMEN
Mezonefric cervical cancer was more prevalent in younger women (mean age 42.2 +/- 1.2 years) with no classic predisposing factors. In most cases (62.1%) the localized stage of the disease (I, II stages) dominated. Regional metastases correlated with depth of tumor invasion (with a depth of invasion of more than 10 mm--57.8%). There was marked low expression of HER2/neu (only in 1 of 14 samples it was revealed light positive reaction. Proliferation index Ki-67 was 37.5% and the signs of mutation in the p53 gene were found in 28.4% of cases. Estimating that two thirds of patients with clear-cervical cancer revealed localized forms of the disease, and that most of the women had received the combination treatment (51.8%)--a 5-year survival rate was quite high and was 79.3%.