RESUMEN
Lymphoma-like lesion (LLL) of the female genital tract is an older term in the literature that describes a florid reactive lymphoid proliferation that can be misinterpreted as lymphoma. Multiple causes of LLL have been suggested but most cases remain unexplained. We describe the clinicopathologic features of 6 patients with LLL involving the uterine cervix. Five patients presented with abnormal Papanicolaou test (Pap smear), and 3 patients had a biopsy procedure performed prior to detection of LLL in a loop electrosurgical excision procedure (LEEP). In each specimen, surface epithelial erosion was associated with a superficial, polymorphous lymphoid infiltrate with numerous scattered large cells, without cellular necrosis or sclerosis. Squamous dysplasia was present in 4 patients. Immunohistochemical studies revealed a mixed population of B- and T-lymphoid cells. T-cells were more numerous but B-cells and formed aggregates or sheets in areas. The large cells were predominantly B-cells positive for CD20 and negative for CD3 in all cases. CD30 was positive 3 cases, and Epstein-Barr virus-encoded RNA was positive in 3 cases. Assessment for clonality in 1 patient using polymerase chain reaction (PCR) methods revealed monoclonal immunoglobulin heavy chain (IgH) gene rearrangements. At last clinical follow-up there was no evidence of progressive or systemic disease. We conclude that LLL of the cervix has a number of etiologies and that a prior surgical procedure, present in 3 patients in this study, is another possible etiology. As has been reported by others, monoclonal IgH gene rearrangements can be detected in this entity which has a benign clinical course.
Asunto(s)
Cuello del Útero/patología , Seudolinfoma/patología , Enfermedades del Cuello del Útero/patología , Adulto , Linfocitos B/inmunología , Femenino , Estudios de Seguimiento , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Linfoma/patología , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Seudolinfoma/diagnóstico , Seudolinfoma/genética , Enfermedades del Cuello del Útero/diagnóstico , Enfermedades del Cuello del Útero/genética , Adulto JovenRESUMEN
Activation of telomerase plays a critical role in unlimited proliferation and immortalization of cells. The purpose of this study was to evaluate the significance of human telomerase reverse transcriptase catalytic subunit (hTERT) as a prognostic marker. The expression of hTERT in a large population of 153 patients with stage I non-small cell lung cancer was analyzed using the in situ hybridization technique. We found that diffuse and clear hTERT expression was present in 51 (33%) of 153 patients. Kaplan-Meier analysis showed that hTERT expression was associated with shorter overall survival (P = 0.04), shorter disease-specific survival (P = 0.03), and shorter disease-free survival (P = 0.02). Multivariate analysis confirmed this independent prognostic value of hTERT expression. Our results indicated that hTERT mRNA expression is associated with malignant tumor progression and poor outcome. hTERT may serve as a useful marker to identify patients with poor prognosis and to select patients with early-stage non-small cell lung cancer who might benefit from adjuvant treatment.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/biosíntesis , Telomerasa/biosíntesis , Anciano , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Causas de Muerte , Proteínas de Unión al ADN , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Hibridación in Situ , Tablas de Vida , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , ARN Mensajero/biosíntesis , ARN Neoplásico/biosíntesis , Análisis de Supervivencia , Telomerasa/genéticaRESUMEN
PURPOSE: Interleukin-10 (IL-10) may play an important role in controlling tumor growth and metastasis. Some reports have shown that IL-10 can be a potent inhibitor of tumor growth, but others suggest that IL-10 expression by the tumor is an adverse prognostic factor. Because normal bronchial epithelial cells constitutively produce IL-10, we decided to test the prognostic value of IL-10 in a well-defined population of patients with stage I non-small cell lung cancer (NSCLC) treated in a single institution. PATIENTS AND METHODS: Using immunohistochemical analysis, we retrospectively analyzed IL-10 expression in specimens from 138 patients with completely resected clinical/radiographic stage I NSCLC for whom clinical follow-up data were available. RESULTS: IL-10 expression was retained (IL-10 labeling index > or = 10%) in 94 patients (68.1%) and lost in 44 patients (31.9%). The duration of overall, disease-specific, and disease-free survival in the 44 patients lacking IL-10 expression was worse than in the 94 patients with IL-10 expression (P = 0.08, 0.02, and 0.05, respectively; Log-rank test). Interestingly, IL-10 expression was observed more frequently in tumors with squamous cell histology than in tumors of other histological subtypes (P = 0.04; chi(2) test). Multivariate analysis confirmed the independent prognostic value of IL-10 expression for disease-specific survival (P = 0.04). CONCLUSION: Lack of IL-10 expression by the tumor was associated with a significantly worse outcome of early stage NSCLC. The mechanisms underlying this clinically and biologically important finding need to be further explored.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Interleucina-10/metabolismo , Neoplasias Pulmonares/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Neoplasias de los Bronquios/metabolismo , Neoplasias de los Bronquios/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
PURPOSE: The PTEN gene at chromosome 10q23.3 is a tumor-suppressor genethat is inactivated in several types of human tumors. Althoughmutation and homozygous deletion are the most commonmechanisms of PTEN inactivation, promoter methylation and translational modification can also account for PTEN silencing. The aim of this study was to investigate the expression of PTEN protein in primary non-small cell lung cancer (NSCLC) samples and to investigate the promoter methylation status of the gene in a panel of NSCLC cell lines as well as primary tumors. EXPERIMENTAL DESIGN: We analyzed PTEN expression by immunohistochemistry in tissue samples from 125 patients with early-stage NSCLC. We also evaluated PTEN promoter methylation status by methylation-specific PCR in 20 microdissected PTEN-negative primary tumors from among the last specimens as well as in a panel of 16 NSCLC cell lines. Western and Northern blotting were performed in the same panel of NSCLC cell lines. RESULTS: Thirty (24%) of the 125 specimens showed a lack of staining for PTEN. PTEN methylation was detected in 7 (35%) of the 20 PTEN-negative NSCLC samples and in none of the 10 PTEN-positive NSCLC samples that were microdissected. Furthermore, PTEN methylation was observed in 11 (69%) of the 16 NSCLC cell lines tested. PTEN mRNA expression was increased in the NCI-H1299 cell line by in vitro treatment with the demethylating agent 5-aza-2'-deoxycytidine. PTEN methylation was well correlated with PTEN expression in NSCLC cell lines by Western and Northern blot (P = 0.025). CONCLUSIONS: Although genetic alterations of the PTEN gene are rare in NSCLC, loss of PTEN protein is not an uncommon event in early-stage NSCLC. Lack of PTEN expression may be partially explained by promoter methylation.
Asunto(s)
Azacitidina/análogos & derivados , Carcinoma de Pulmón de Células no Pequeñas/patología , Metilación de ADN , Neoplasias Pulmonares/patología , Monoéster Fosfórico Hidrolasas/genética , Regiones Promotoras Genéticas/genética , Proteínas Supresoras de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/farmacología , Azacitidina/farmacología , Northern Blotting , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/genética , Células Cultivadas , Metilasas de Modificación del ADN/antagonistas & inhibidores , ADN de Neoplasias/genética , ADN de Neoplasias/metabolismo , Decitabina , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Fosfohidrolasa PTEN , Monoéster Fosfórico Hidrolasas/metabolismo , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células Tumorales Cultivadas , Proteínas Supresoras de Tumor/metabolismoRESUMEN
It is well documented that nevus cells can be found within the fibrous capsule and trabeculae of lymph nodes; however, it is less well known that nevus cells can also be found in the lymph node parenchyma. We report the findings in 13 cases of nevus cell aggregates located within the cortical and/or medullary parenchyma of lymph nodes. Seven of the 13 patients had a primary diagnosis of melanoma, three had no known malignancy, one had breast carcinoma, one had adnexal carcinoma of the skin, and one had squamous cell carcinoma of the tonsil. Of the seven patients with melanoma, four had axillary lymph node dissections and three had inguinal lymph node dissections. The patient with adnexal carcinoma had metastatic carcinoma in 14 of 20 lymph nodes that had been dissected; one of them also had intraparenchymal nevus cells. The patient with squamous cell carcinoma of the tonsil had an intraparenchymal nevus cell aggregate in one of the 21 dissected lymph nodes; all 21 were negative for carcinoma. Nests of intraparenchymal nevus cells ranged from clusters of only a few cells up to 2.1-mm aggregates. No mitotic figures, prominent nucleoli, or lymphatic-vascular invasion were detected in any of the melanocytic aggregates. The melanocytic cells of the nevus cell aggregates expressed S-100 protein and/or MART-1 but not gp100 protein (HMB-45). Less than 1% of the nevus cells expressed Ki-67. The purpose of this study was to draw attention to the finding of nevus cells in the parenchyma of lymph nodes and to alert pathologists to this as a potential diagnostic pitfall, especially in patients with concurrent melanoma or carcinoma. Awareness that nevus cells can be present in nodal parenchyma, analysis of their morphologic features (including comparison with any previous or existing melanoma or carcinoma), and immunophenotyping will help pathologists to establish the correct diagnosis in most instances.
Asunto(s)
Ganglios Linfáticos/patología , Melanoma/diagnóstico , Nevo/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adulto , Anciano , Biomarcadores/análisis , Errores Diagnósticos , Femenino , Granulocitos , Humanos , Técnicas para Inmunoenzimas , Isoantígenos/metabolismo , Ganglios Linfáticos/metabolismo , Masculino , Persona de Mediana Edad , Nevo/metabolismo , Proteínas S100/metabolismoRESUMEN
Basal cell nevus syndrome is a genetically determined disease characterized by 5 major manifestations (multiple basal cell carcinomas, jaw cysts, skeletal abnormalities, pits of the hands and feet, and ectopic calcification) and a variety of developmental anomalies. We present a case of basal cell nevus syndrome in which the patient had adenoid cystic carcinoma of the minor salivary glands develop in the soft palate resulting in distant pulmonary metastases. The patient died at the age of 44 years of respiratory complications. To our knowledge, this is the first simultaneous occurrence of basal cell nevus syndrome with adenoid cystic carcinoma of salivary gland.