RESUMEN
BACKGROUND: Understanding the mechanism of prostate cancer metastasis is essential to the design of a more effective therapy. An effective therapy for this disease will depend on the development of a clinically relevant in vivo model. PURPOSE: We describe the development of such a model by using orthotopic implantation of human prostate cells in BALB/c nude mice. METHOD: We compared the tumorigenicity of and the incidence of metastasis of human prostate cancer PC-3M and LNCaP-FGC (LNCaP) cell lines subsequent to prostatic (orthotopic) or subcutaneous (ectopic) implantations in male nude mice. RESULTS: LNCaP cells produced tumors only in the prostate. Enhanced tumorigenicity at the orthotopic site was found for PC-3M cells. Lymph node metastases were observed in practically all mice given an injection of PC-3M cells in the prostate, but they were uncommon with subcutaneous injection of these cells. Bilateral orchiectomy did not alter the tumorigenicity of either PC-3M or LNCaP cells or the incidence of lymph node metastasis by PC-3M cells. LNCaP tumors in the mouse prostate (but not PC-3M tumors) elaborated detectable levels of human prostate-specific antigen (PSA) in the serum, even when tumors were small (1.5 mm in diameter). Immunohistochemistry analysis revealed the presence of the PSA marker in tissue sections of LNCaP but not of PC-3M tumors. CONCLUSIONS: The implantation of human prostate cancer cells in an ectopic environment does not permit expression of metastatic potential. In contrast, intraprostatic implantation does. IMPLICATIONS: These data suggest that the orthotopic injection of human prostate cancer cells into the nude mouse may provide a valuable model to study the biology and therapy of human prostate cancer.
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Modelos Animales de Enfermedad , Metástasis de la Neoplasia/patología , Neoplasias de la Próstata/patología , Animales , Antígenos de Neoplasias/análisis , Biomarcadores de Tumor/sangre , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Colagenasa Microbiana/biosíntesis , Invasividad Neoplásica , Antígeno Prostático Específico , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/enzimología , Trasplante Heterólogo , Células Tumorales CultivadasRESUMEN
Murine hybridomas were generated against purified carcinoembryonic antigen (CEA), and their monoclonal antibodies (MAb) were assayed for their ability to recognize specific CEA epitopes. One of the MAb, designated 7F, was found to recognize an epitope of CEA that was expressed in human colonic carcinoma tissues but not in normal colonic tissues. When extracts of 13 colonic carcinoma tissues and 9 normal colonic tissues were examined with the Western blot technique using MAb 7F, 11 colonic carcinoma tissues (85%) reacted with 7F, but none of the 9 normal colonic tissues (including many obtained from the areas adjacent to the colonic carcinomas) did. Western blot analysis indicated a Mr 180,000 band in 11 of 13 (85%) colonic carcinoma extracts. The limit of detectability of CEA was 0.5 micrograms/lane. According to immunohistochemical techniques, 16 of 18 (89%) formalin-fixed paraffin-embedded sections of colonic carcinomas reacted with MAb 7F, whereas 9 of 9 (100%) frozen sections of colonic carcinomas reacted with the antibody. Of the 32 paraffin-embedded and frozen sections of normal colonic tissues examined, none showed any reactivity with MAb 7F. MAb 7F did not react with nonspecific cross-reacting antigen either. This antibody has been examined for its usefulness in detecting CEA in suspension and has been found to work both in sandwich enzyme-linked immunosorbent assays and in sandwich radioimmune assays. The detection of CEA in colon tumors but not in normal colonic tissues may be attributed to two possible explanations. It is possible that the level of CEA expression in normal colonic tissue is below the sensitivity of the assays employed. Alternatively, MAb 7F may recognize a "specific" epitope of CEA which was found in colon tumors but not in CEA of normal colonic tissues. At the present time, it is not possible to discern between these two possibilities. Nevertheless, MAb 7F was capable of detecting the differential expression of CEA in colonic carcinomas and, therefore, may be useful for the immunodiagnosis, radioimaging, and immunotherapy of colon cancer.
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Anticuerpos Monoclonales/inmunología , Antígenos de Neoplasias/inmunología , Antígeno Carcinoembrionario/inmunología , Carcinoma/inmunología , Colon/inmunología , Neoplasias del Colon/inmunología , Anticuerpos Antineoplásicos/inmunología , Western Blotting , Ensayo de Inmunoadsorción Enzimática , Epítopos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/inmunología , RadioinmunoensayoRESUMEN
PURPOSE: The objectives of this study were to assess clinical outcomes and prognostic factors in unselected, consecutive patients with poorly differentiated carcinoma (PDC) or poorly differentiated adenocarcinoma (PDA). PATIENTS AND METHODS: The 1,400 patients analyzed were referred to our unknown-primary tumor (UPT) clinic from January 1, 1987 through July 31, 1994. Clinical data from these patients were entered into a computerized data base for storage, retrieval, and analysis. Survival was measured from the time of diagnosis; survival distribution was estimated using the product-limit method. Multivariate survival analyses were performed using proportional hazards regression and by recursive partitioning. RESULTS: Nine hundred seventy-seven patients were diagnosed with unknown-primary carcinoma (UPC) and 337 of these patients had PDC or PDA. No clinical differences were identified among patients with PDC, PDA, or UPC patients with other carcinoma or adenocarcinoma subtypes. PDC patients enjoyed better survival than PDA patients. Poor cellular differentiation was not an important prognostic variable. Variables predictive of survival included lymph node metastases, sex, number of metastatic sites, histology (PDC v PDA), and age. Although chemotherapy did not appear to influence survival for the entire group of PDC or PDA patients, a subset of patients with good prognostic features experienced median survival durations of up to 40 months. CONCLUSION: The long median survival and chemotherapy responsiveness of UPC patients with PDC and PDA could not be confirmed. However, subpopulations with prolonged median survival durations could be defined, and the value of chemotherapy in this group remains to be determined. Identification and exclusion of treatable or slow-growing malignancies may account for the poor survival of the PDC and PDA patients reported in this study.
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Adenocarcinoma/mortalidad , Carcinoma/mortalidad , Neoplasias Primarias Desconocidas/mortalidad , Adenocarcinoma/sangre , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Carcinoma/sangre , Carcinoma/tratamiento farmacológico , Carcinoma/patología , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Proteínas de Neoplasias/sangre , Neoplasias Primarias Desconocidas/sangre , Neoplasias Primarias Desconocidas/tratamiento farmacológico , Neoplasias Primarias Desconocidas/patología , Pronóstico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
A patient with systemic lupus erythematosus (SLE) and lupus retinopathy showed resolution of subretinal edema documented with fluorescein angiography. Subsequently at autopsy, immunofluorescence studies disclosed ocular deposition of immunoglobulins in the vascular layer of choroid capillaries and basement membranes of ciliary processes and bulbar conjunctivas. To our knowledge, these findings represent the first reported documentation of probable immune-complex ocular vasculitis in lupus retinopathy using immunofluorescent techniques, and they support the hypothesis that lupus retinopathy is caused by immune complex deposition as are other manifestations of SLE.
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Oftalmopatías/etiología , Ojo/inmunología , Enfermedades del Complejo Inmune/etiología , Lupus Eritematoso Sistémico/inmunología , Adolescente , Coroides/inmunología , Proteínas del Sistema Complemento/análisis , Conjuntiva/inmunología , Edema/etiología , Edema/inmunología , Ojo/irrigación sanguínea , Femenino , Humanos , Inmunoglobulina A/aislamiento & purificación , Inmunoglobulina G/aislamiento & purificación , Inmunoglobulina M/aislamiento & purificación , Properdina/análisis , Enfermedades de la Retina/etiología , Enfermedades de la Retina/inmunología , Vasculitis/etiología , Vasculitis/inmunologíaRESUMEN
In preparation for a clinical trial of the recombinant p53 adenovirus Ad5CMV-p53 for the treatment of lung cancer, the potential adverse effects of Ad5CMV-p53 were assessed in vitro and in vivo. No infectious replication of Ad5CMV-p53 was detectable in HeLa cells infected with extracts from HeLa cells previously infected with Ad5CMV-p53. No Ad5CMV-p53 DNA replication was detected by 32Pi labeling in lung cancer cells infected with Ad5CMV-p53 at multiplicities of infection (moi) up to 1,000 pfu/cell (total of 5 x 10(9) pfu viruses). The infectivity and cytotoxicity of Ad5CMV-p53 were examined in vitro in normal human bronchial epithelial (NHBE) cells. At a moi of 50 pfu/cell, Ad5CMV-p53 infection and expression were detectable in 80% of the treated cells. The exogenous p53 protein was first detected by western blotting at 8 hr and peaked at 48 hr after infection. Growth of NHBE cells was not affected by Ad5CMV-p53 infection at a moi of 100 pfu/cell. The pathogenicity of Ad5CMV-p53 was assessed in BALB/c mice. The virus was given to four groups of mice by intratracheal injection at dosages from 10(7) to 10(10) pfu; a fifth group received phosphate-buffered saline alone. None of the viral injections proved to be lethal. Mild to moderate peribronchiolar and perivascular infiltration by mononuclear cells and lymphocytes, with patches of pneumonitis, was the most acute toxic effect detected by histologic analysis in the two high-dose groups. Immunohistochemical analysis of the same paraffin-embedded sections showed that infectivity and level of expression of p53 in lung tissue were dose-dependent. Our results demonstrate that Ad5CMV-p53 is a replication-defective virus that yields a relatively low degree of acute toxicity in mice; these data document a safety profile encouraging for clinical trials of Ad5CMV-p53 in the therapy of lung cancer.
Asunto(s)
Adenovirus Humanos/genética , Genes p53/genética , Vectores Genéticos/toxicidad , Proteína p53 Supresora de Tumor/toxicidad , Adenovirus Humanos/patogenicidad , Adenovirus Humanos/fisiología , Animales , Bronquios/citología , Células Cultivadas , Replicación del ADN , Células Epiteliales , Vectores Genéticos/genética , Células HeLa , Humanos , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Replicación ViralRESUMEN
Punch biopsies were examined by indirect immunofluorescence for immune complex deposits containing C-type viral antigen. Antisera specific for immunoglobulins and HEL-12 virus mediated fluorescence at the dermal-epidermal junction and in vessel walls of 16 of 16 biopsies involved skin from patients with systemic lupus erythematosus (SLE). Preimmune sera did not mediate fluorescence and gradient purified HEL-12 virus, simian sarcoma virus and baboon endogenous virus but not Rous sarcoma virus blocked the reaction of anti-HEL-12 virus serum with SLE tissue. Ten biopsies from uninvolved skin of the patients with SLE did not react with the antiviral serum, nor did tissue from 9 patients with discoid lupus erythematosus, psoriasis, bullous pemphigoid or normal skin. These data support the hypothesis that C-type viral immune complexes participate in the pathogenesis of SLE.
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Complejo Antígeno-Anticuerpo , Lupus Eritematoso Sistémico/inmunología , Retroviridae/inmunología , Animales , Especificidad de Anticuerpos , Haplorrinos , Humanos , Sueros Inmunes , Piel/inmunologíaRESUMEN
Among 1324 patients with well differentiated (papillary, follicular, Hurthle cell) thyroid carcinoma treated at the University of Texas M. D. Anderson Hospital and Tumor Institute between January 1950 and July 1984, 125 had a history of external irradiation to the head and neck region during childhood. This study was a comparison of the characteristics and disease course of thyroid carcinoma in these patients with those of patients who had not received such irradiation. Each irradiated patient was matched to 3 nonirradiated patients by age, sex, and extent of disease. The groups had similar distributions of histological type of lesion, surgical procedures, and number of patients who received radioactive iodine as part of their initial treatment. The two groups' recurrence and mortality rates were similar as well, although patients who had head and neck irradiation as children more often presented with thyroid cancer not limited to the thyroid gland and bilateral thyroid lobe involvement (P less than 0.005). The data indicate that patients who received head and neck irradiation have, at the time of diagnosis, more extensive thyroid carcinoma. However, the prognosis of well differentiated thyroid carcinoma in patients who have a history of head and neck irradiation is similar to that in patients without such a history.
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Cabeza/efectos de la radiación , Cuello/efectos de la radiación , Neoplasias Inducidas por Radiación/patología , Neoplasias de la Tiroides/etiología , Adulto , Factores de Edad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/mortalidad , Neoplasias Inducidas por Radiación/terapia , Factores Sexuales , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapiaRESUMEN
Well differentiated thyroid carcinoma was diagnosed in 1,127 patients at The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston from 1951 to 1981. Of those 1,127 patients, 101 had documented pulmonary metastasis. A retrospective analysis was conducted, and these patients were followed up until 1983. The primary tumors in these patients were histologically classified as papillary (67%), follicular (22%), or Hurthle cell (11%). The age at diagnosis ranged from 5-87 yr. Lung metastasis was diagnosed by both chest x-ray and positive uptake of 131I in 49 patients. Forty-two patients had positive chest x-ray results and negative 131I scans, and 10 patients had positive 131I scans and negative chest x-ray results. The patients were treated with radioactive iodine (76%), chemotherapy (9%), external radiotherapy (2%), or supportive care only (14%). Sixty-seven patients subsequently died of thyroid carcinoma. Our studies showed the following. 1) Patients who were younger than 40 yr of age at diagnosis had better prognosis (71% survival) compared with those over 40 yr of age (16% survival; P less than 0.01). 2) Uptake of radioactive iodine by lung metastasis is a favorable prognostic factor, especially in patients with negative radiological findings. Patients treated with radioactive iodine have a longer survival than those not treated with radioactive iodine (P less than 0.002). 3) The incidence of pulmonary metastasis is significantly less in patients who are treated by total thyroidectomy than in those treated with less than total thyroidectomy (P less than 0.03). 4) The incidence of pulmonary metastasis is lowest in patients with papillary carcinoma (9%), compared with that in patients with follicular (13%) or Hurthle cell (25%) carcinoma.
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Carcinoma/radioterapia , Radioisótopos de Yodo/uso terapéutico , Neoplasias Pulmonares/secundario , Neoplasias de la Tiroides/radioterapia , Adolescente , Adulto , Factores de Edad , Anciano , Carcinoma/patología , Carcinoma/secundario , Niño , Preescolar , Femenino , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Factores Sexuales , Neoplasias de la Tiroides/patologíaRESUMEN
This study was undertaken to evaluate the prognostic value of calcitonin (CT) immunostaining in medullary carcinoma of the thyroid (MCT). Primary tumors and metastases from 44 patients with MCT were stained for CT using the immunoperoxidase method. According to the number of cells stained in the primary tumors, the patients were subdivided into 3 groups. Group A included 9 patients with CT-poor tumors (less than 25% of cells stained), group C consisted of 21 patients with CT-rich tumors (greater than 75% of cells stained), and group B included 14 patients with intermediate tumors (25-75% of cells stained). Group A and B patients presented with more advanced disease and had a higher rate of recurrence than group C patients, but the difference was not statistically significant. The number of cells stained correlated well with survival, which was significantly longer for group C than groups B (P = 0.044) and A (P = 0.001). Group B patients survived longer than did those of group A (P = 0.036). The 5-yr survival rates were 52.7%, 93%, and 100% for groups A, B, and C, respectively. Eighty-three percent of patients with multiple endocrine neoplasia IIa had CT-rich tumors, whereas 78.3% of those with sporadic disease had CT-poor ones (P less than 0.001). CT-rich metastases were compatible with prolonged survival even if they were affecting vital organs, whereas CT-poor metastases were virulent and carried a poor prognosis. Therefore, CT immunostaining is recommended for all patients with MCT, as it can predict the course of the disease. It also can be used as a staging procedure and may help the clinician in making a decision regarding the therapeutic approach.
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Calcitonina/análisis , Carcinoma/patología , Neoplasias de la Tiroides/patología , Adulto , Anciano , Carcinoma/mortalidad , Carcinoma/secundario , Femenino , Histocitoquímica , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Coloración y Etiquetado , Neoplasias de la Tiroides/mortalidadRESUMEN
Effects of gestation on volume homeostasis and renal function were studied in awake spontaneously hypertensive rats (SHR). Systolic blood pressure was similar to that of virgin littermates during most of SHR pregnancy but decreased near term (p less than 0.005). Plasma renin activity was lower in SHR than in age-matched Wistar-Kyoto (WKY) rats (p less than 0.001), but values were similar in gravid and nonpregnant animals from each strain. Renal renin content and lipid volume fractions of papillary interstitial granules were significantly greater in pregnant animal of each strain and those of the gravid WKY were also greater than both pregnant and virgin SHR. Saralasin had no effect on mean arterial pressure in gravid and virgin rats from either group. Plasma volume increased significantly near term in animals of both strains. Kidney weight, glomerular filtration rate (GFR), and renal blood flow were lower in SHR compared to WKY, and the hypertensive rats failed to demonstrate an increase in GFR during gestation, unlike the WKY. All SHR and pregnant WKY excreted infused sodium better than the virgin WKY. Also, regular Wistar animals excreted a salt load better than the virgin WKY. Finally, uterine blood flow, pup number and conceptus weight were similar in SHR and WKY. We conclude that pregnancy induces a decrease in blood pressure in SHR, and that angiotensin II does not seem to play an important role in maintaining blood pressure during gestation in either SHR or WKY. Despite a lower GFR and its failure to increase during pregnancy, renal sodium handling is not impaired in the SHR. The virgin WKY has a decreased ability to excrete sodium which is ameliorated during gestation.
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Presión Sanguínea , Hipertensión/fisiopatología , Riñón/fisiopatología , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Animales , Femenino , Tasa de Filtración Glomerular , Hemodinámica , Médula Renal/patología , Metabolismo de los Lípidos , Natriuresis , Volumen Plasmático , Embarazo , Ratas , Ratas Endogámicas , Sistema Renina-AngiotensinaRESUMEN
This study analyzed the impact of prognostic variables of age, sex, histopathological diagnosis, extent of disease at diagnosis, and surgical intervention on well differentiated thyroid carcinoma and how surgical treatment, radioactive iodine, and radiotherapy influence the patients' outcomes. There have been 1599 patients with well differentiated thyroid cancer treated and followed at the University of Texas M.D. Anderson Cancer Center from 1948 to 1989. The median follow-up for all patients was 11.0 yr, with the maximum follow-up being 43 yr and the minimum follow-up being 1 yr. The patients were predominantly female (2.3:1), with papillary (81%) and intrathyroidal carcinomas (42%) at the time of diagnosis. Sixty-six percent of the patients had a total thyroidectomy, 7% received external radiotherapy, and 46% had radioactive iodine as part of the treatment of the original disease; the overall recurrence rate was 23%, and the death rate was 11%. This study showed that treatment with radioactive iodine was the single most powerful prognostic indicator for increased disease-free interval (P less than 0.001) and that its use significantly increased survival as well. No benefit was obtained from treatment with external radiotherapy. Children had the best overall survival, but of the adult patients, females who had intrathyroidal papillary disease treated with total thyroidectomy, who had been given radioactive iodine, and whose disease had been diagnosed between 20-59 yr of age had the best prognosis.
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Carcinoma/terapia , Neoplasias de la Tiroides/terapia , Adolescente , Adulto , Carcinoma/patología , Carcinoma/radioterapia , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Radioisótopos de Yodo/uso terapéutico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Cuidados Posoperatorios , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/radioterapia , TiroidectomíaRESUMEN
The natural history and prognostic factors of medullary carcinoma of the thyroid (MCT) were studied in 161 patients seen at the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston between 1944 and 1983. One hundred twenty-five patients (77.6%) had the sporadic variety of MCT, 31 patients (19.3%) had multiple endocrine neoplasm (MEN) type IIa and 5 patients (3.1%) had MEN-IIb. The disease occurred equally in both sexes (M:F ratio 1:1.05). Thyroid nodules were the most common presenting feature especially in patients with the sporadic disease and MEN-IIb. Fifteen patients with MEN-IIa had occult MCT; the diagnosis was made through screening of family members with calcitonin measurement before and after stimulation with calcium or pentagastrin. Sixteen patients with MEN-II had pheochromocytoma and 7 had hyperparathyroidism. Total thyroidectomy was the most commonly performed operation. The lowest incidence of recurrence occurred in patients who underwent total thyroidectomy and modified neck dissection. Radioactive 131I was used as adjunct to surgery in 19 patients but it did not improve the survival or lower the incidence of recurrence. Patients who received postoperative radiotherapy had significantly lower adjusted survival rates than those treated by surgery alone, but we tended to irradiate patients with more advanced disease. Chemotherapy was administered to 11 patients with disseminated metastases but the response was poor. The 5- and 10-year adjusted survival rates of all the patients with MCT were 78.2% and 61.4%, respectively. Patients with MEN-IIa had much better rates than patients with sporadic disease (p = 0.0005), who were 7.74 times more likely to die of MCT. The stage of the disease at presentation was a major prognostic factor. Patients with stages III or IV disease were 7.31 times more likely to die of MCT than those with stages I or II. There was no significant difference in survival between patients with stages I and II or III and IV. The presence of cervical lymph node metastases did not affect the survival adversely. Direct extension with involvement of tissue was a bad prognostic sign. Patients younger than 40 years old at the time of diagnosis of MCT had a significantly better adjusted survival rate than those who were older. Women had a better prognosis than men, who were 1.89 times more likely to die of MCT. Diarrhea was a bad prognostic sign. However, it occurred more frequently in patients with advanced stages of the disease and larger tumor mass.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Carcinoma/patología , Neoplasias de la Tiroides/patología , Adolescente , Neoplasias de las Glándulas Suprarrenales/patología , Adulto , Anciano , Carcinoma/mortalidad , Carcinoma/terapia , Niño , Terapia Combinada , Femenino , Enfermedades Gastrointestinales/complicaciones , Humanos , Hiperparatiroidismo/complicaciones , Radioisótopos de Yodo/uso terapéutico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Primarias Múltiples/patología , Feocromocitoma/patología , Pronóstico , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/terapia , TiroidectomíaRESUMEN
To determine whether IL-1 alpha and/or IL-1 beta protein is expressed by human melanoma tumor in vivo, we first analyzed nine human melanoma cell lines and optimized the in situ detection of these proteins. Three of the melanoma cell lines stained positively for both IL-1 alpha and IL-1 beta using immunohistochemistry (IHC). THe specificity of IHC was confirmed by the ability of purified recombinant IL-1 alpha and IL-1 beta protein to abolish the staining after being adsorbed by their respective antibodies before use in IHC. The three positively staining cell lines were also the only lines to demonstrate IL-1 production by western blot analysis as well as IL-1 secretion by ELISA. Next we examined 29 surgically obtained melanoma tumor specimens (6 primary and 23 metastases) that had been formalin fixed and paraffin embedded. Using the same anti-IL-1 antibodies, 5 of 23 metastatic tumors stained positively. None of the 6 primary lesions stained for either IL-1 alpha or IL-1 beta. Comparison of staining pattern performed on serially sectioned tissue using preimmune serum and antibodies against S-100 protein, melanoma-associated antigen (HMB-45), and CD68 (kappa P1), which recognizes monocyte-macrophage cell lineage, demonstrates for the first time that IL-1 protein is produced by human melanoma tumor cells in vivo. These findings provide the basis for examination of what may be a previously unrecognized biologically distinct subset of patients.
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Interleucina-1/biosíntesis , Melanoma/metabolismo , Análisis de Varianza , Especificidad de Anticuerpos , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Antígenos de Neoplasias/análisis , Humanos , Inmunohistoquímica , Melanoma/patología , Melanoma/cirugía , Antígenos Específicos del Melanoma , Proteínas de Neoplasias/análisis , Reproducibilidad de los Resultados , Proteínas S100/análisis , Células Tumorales CultivadasRESUMEN
A 37-year-old woman presented with acute psychosis and cognitive impairment. Skull x-ray showed an enlarged sella turcica with erosion of the floor. Endocrinologic workup suggested the diagnosis of Cushing's disease and hyperprolactinemia. She had no cushingoid feature, and the only physical sign was mild generalized obesity. She showed a paradoxic response to dexamethasone suppression, and underwent trans-sphenoidal resection of a pituitary macroadenoma. Electron microscopy showed the tumor to be a Crooke's cell adenoma. Results of immunohistochemical staining were positive only for ACTH and beta-endorphin. The neuropsychiatric manifestations resolved after surgery.
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Adenoma/diagnóstico , Síndrome de Cushing/diagnóstico , Neoplasias Hipofisarias/diagnóstico , Trastornos Psicóticos/diagnóstico , Adenoma/ultraestructura , Adulto , Síndrome de Cushing/patología , Femenino , Humanos , Microscopía Electrónica , Neoplasias Hipofisarias/ultraestructuraRESUMEN
PURPOSE: The prognostic influence of 6 biomarkers correlated to histologic subtypes of non-small cell lung cancer (NSCLC) on loco-regional control, overall survival, disease-free survival (DFS), and distant disease control (DDC) rates, all measured at 5 years, were examined. MATERIALS & METHODS: Cell blocks from the primary tumors of 137 patients with pathologically staged N1 NSCLC at MDACC were analyzed by 6-biomarker status correlated to histological subtypes and their outcomes. RESULTS: The ranges of biomarker values were as follows: apoptotic index, 0.2-2.8%; mitotic index, 0-1.8%; the proportion of cells in S+G2M, 3-36%; p53 status, 0-100%; Ki-67, 0-9.3%; DNA index, 1.0-2.74. Subtypes of 137 cases from the postoperative pathology specimen showed that 74 patients had squamous carcinoma and 63 patients had adenocarcinoma. Mean and median lengths of follow-up were 4.21 years and 2.43 years, respectively. Patients with squamous cell carcinoma (SCC) had a better 5-year survival (p = 0.006), DFS (p = 0.002), and distant metastasis control (p = 0.002) than patients with adenocarcinoma (AC). Among patients with AC, the DNA index was a significant predictor of 5-year DFS (p = 0.02), DDC rate (p = 0.04), and local-regional control (p < 0.05). Higher apoptosis (p = 0.03) and mitosis indices (p = 0.03) were also univariate predictors of increased distant disease among patients with AC. Multivariate analysis of patients with AC revealed that the DNA index and Ki-67 were the only significant independent predictors of distant metastasis (p < 0.04 and p < 0.02, respectively) and DFS (p < 0.04 for both). Among patients with SCC, univariate analysis showed that S+G2M proportion (p < 0.05) and Ki-67 levels (p < 0.02) were significant predictors for local-regional control; for SC, multivariate analysis showed that only mitosis was a significant predictor in this case for overall survival (p < 0.04). CONCLUSION: Spontaneous apoptotic index and Ki-67 were significantly higher in SC than in AC. Patients with SC had less distant metastasis better DFS and overall survival than those with AC. Multivariate analysis revealed that DNA index and Ki-67 status were significant predictors for DDC and DFS in patients with AC, but only mitotic index was a significant predictor of overall survival for patients with SCC.
Asunto(s)
Adenocarcinoma/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Neoplasias Pulmonares/patología , Adenocarcinoma/genética , Adenocarcinoma/inmunología , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Análisis de Varianza , Apoptosis , Biomarcadores , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , ADN de Neoplasias/análisis , Femenino , Estudios de Seguimiento , Marcadores Genéticos , Humanos , Antígeno Ki-67/análisis , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Índice Mitótico , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
Despite numerous histochemical, ultrastructural, and immunohistochemical studies, differentiation between malignant epithelial pleural mesothelioma and adenocarcinoma of the lung remains extremely difficult. Although there is general agreement that immunohistochemical methods can aid in this distinction, some studies have produced conflicting results with some of the proposed markers for mesothelioma. To obtain comparable and reproducible results, 19 unequivocal epithelial mesotheliomas and 23 unequivocal primary lung adenocarcinomas were studied by the avidin-biotin-peroxidase complex method on formalin-fixed, paraffin-embedded tissue specimens. Well-characterized, commercially available antibodies to carcinoembryonic antigen (CEA), a high- and low-molecular-weight keratin, vimentin, epithelial membrane antigen, human milk fat globule, Leu-M1, TAG-72 (identified by monoclonal antibody B72.3), beta 1 pregnancy-specific glycoprotein (SP1), human placental lactogen, secretory component (SC), CA19-9, and S-100 protein were used. Twenty-one adenocarcinomas (91.3%) reacted for CEA, 14 (60.9%) for Leu-M1, 14 (60.9%) for SC, nine (39.1%) for CA19-9, and eight (34.8%) for SP1; no mesotheliomas stained for any of these markers. Nineteen adenocarcinomas (82.6%) and one mesothelioma (5.3%) reacted with B72.3. Adenocarcinomas and mesotheliomas did not significantly vary in reaction to the remaining antibodies. None of the antibodies used was specific for mesothelioma, but CEA was the single most useful marker. One of the two adenocarcinomas negative for CEA was positive for TAG-72, Leu-M1, and SC, and the only B72.3-positive mesothelioma was negative for CEA, Leu-M1, SC, CA19-9, and SP1. These findings indicate that greater sensitivity in differentiating mesothelioma and adenocarcinoma can be achieved by immunostaining for both CEA and one or more of the markers TAG-72 (B72.3), Leu-M1, SC (these three have the highest sensitivity and specificity after CEA), CA19-9, and SP1.
Asunto(s)
Adenocarcinoma/diagnóstico , Antígenos de Neoplasias/análisis , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Neoplasias Pleurales/diagnóstico , Adenocarcinoma/análisis , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Diagnóstico Diferencial , Femenino , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/análisis , Neoplasias Pulmonares/patología , Masculino , Mesotelioma/análisis , Mesotelioma/patología , Ratones , Persona de Mediana Edad , Neoplasias Pleurales/análisis , Neoplasias Pleurales/patología , ConejosRESUMEN
The distinction between malignant pleural mesotheliomas and adenocarcinomas, particularly those originating in the lung, is a difficult diagnostic problem that can be facilitated by the use of immunohistochemical markers. In this study, the immunoreactivity of thyroid transcription factor-1 (TTF-1), E-cadherin, BG8, WT1, and CD44S was investigated in 50 epithelial mesotheliomas, and 40 pulmonary and 95 nonpulmonary adenocarcinomas. After analyzing the results, it was concluded that E-cadherin and BG8 are useful markers for distinguishing between epithelial mesotheliomas and adenocarcinomas of various origins, including the lung. Because TTF-1 expression is found almost exclusively in adenocarcinomas of the lung but is absent in mesotheliomas, immunostaining for this marker is particularly useful for distinguishing between these two malignancies. Although WT1 immunostaining may also be useful, its value, as determined in this study, is lower than that reported by other investigators. CD44S immunostaining does not have any practical value in discriminating between epithelial mesothelioma and lung adenocarcinoma.
Asunto(s)
Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/análisis , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Neoplasias Pleurales/diagnóstico , Adenocarcinoma/química , Adenocarcinoma/secundario , Cadherinas/análisis , Proteínas de Unión al ADN/análisis , Diagnóstico Diferencial , Células Epiteliales/química , Células Epiteliales/patología , Humanos , Receptores de Hialuranos/análisis , Antígenos del Grupo Sanguíneo de Lewis/análisis , Neoplasias Pulmonares/química , Mesotelioma/química , Proteínas Nucleares/análisis , Neoplasias Pleurales/química , Factor Nuclear Tiroideo 1 , Factores de Transcripción/análisis , Proteínas WT1RESUMEN
Deciduoid mesothelioma is the designation given to an unusual morphologic variant of epithelial mesothelioma that closely simulates exuberant ectopic decidual reaction. Because all four previously reported cases involved the peritoneum and occurred in young women without a history of asbestos exposure, it was suggested that deciduoid mesothelioma was a subtype of epithelial mesothelioma characterized by its unique morphology, that it affects a distinct patient population, and that it is unrelated etiologically to asbestos. The author reports four cases of mesothelioma with deciduoid features, all of which originated in the pleura. Three of the patients were men and one was a woman. Their ages ranged from 46 to 78 years (mean age, 67 yrs). Two of the patients had a history of asbestos exposure. These findings indicate that this morphologic variant of mesothelioma is not limited to a specific patient population nor is it restricted to the peritoneum.
Asunto(s)
Mesotelioma/patología , Neoplasias Pleurales/patología , Anciano , Amianto/efectos adversos , Niño , Decidua/patología , Exposición a Riesgos Ambientales , Femenino , Humanos , Inmunohistoquímica , Masculino , Mesotelioma/diagnóstico , Mesotelioma/cirugía , Persona de Mediana Edad , Pleura/patología , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/cirugía , NeumonectomíaRESUMEN
The distinction between small cell lung carcinoma (SCLC) and small cell carcinomas of other sites is difficult by routine histology. Thyroid transcription factor-1 (TTF-1) is a homeodomain-containing transcription factor that is selectively expressed in thyroid and pulmonary epithelial cells. TTF-1 expression has also been demonstrated in adenocarcinomas of the thyroid and lung, and SCLC. However, the value of TTF-1 immunostaining in discriminating between SCLC and nonpulmonary small cell carcinomas has not been investigated. In the present study using an immunoperoxidase staining procedure on paraffin sections, we investigated the expression of TTF-1 and cytokeratin 20 (CK20), a marker that has previously been demonstrated in small cell carcinomas of the skin (Merkel cell carcinomas), in 82 small cell carcinomas from a wide variety of sites (28 lung, 18 skin, 12 gastrointestinal tract, 8 sinonasal, 5 bladder, 3 prostate, 3 uterine cervix, 2 thyroid, 2 salivary gland, and 1 pancreas). Twenty-seven (96%) of the 28 SCLCs were positive for TTF-1. Among the nonpulmonary small cell carcinomas, two tumors of the gastrointestinal tract, one of the bladder, and one of the uterine cervix exhibited TTF-1 positivity. Sixteen (89%) of the 18 Merkel cell carcinomas and one SCLC were CK20-positive. All other small cell carcinomas were negative for this marker. These results indicate that although TTF-1 is not a specific marker for SCLC, it may assist in distinguishing SCLC from some nonpulmonary small cell carcinomas, particularly Merkel cell carcinoma, especially when it is used in conjunction with CK20.
Asunto(s)
Biomarcadores de Tumor/biosíntesis , Carcinoma de Células Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Nucleares/biosíntesis , Factores de Transcripción/biosíntesis , Carcinoma de Células de Merkel/diagnóstico , Carcinoma de Células de Merkel/metabolismo , Carcinoma de Células de Merkel/patología , Carcinoma de Células Pequeñas/diagnóstico , Carcinoma de Células Pequeñas/patología , Diagnóstico Diferencial , Femenino , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/patología , Humanos , Técnicas para Inmunoenzimas , Proteínas de Filamentos Intermediarios/biosíntesis , Queratina-20 , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Masculino , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/metabolismo , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Adhesión en Parafina , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/metabolismo , Neoplasias de las Glándulas Salivales/patología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Factor Nuclear Tiroideo 1 , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patologíaRESUMEN
The distinction between pleural mesothelioma and peripheral pulmonary adenocarcinoma involving the pleura continues to be a diagnostic problem in surgical pathology. In recent years, the use of various immunohistochemical markers to facilitate this differential diagnosis has become common. In this study, the value of monoclonal antibodies 44-3A6, SM3, HBME-1, and thrombomodulin is compared in the differentiation of these conditions. Fifteen (68.2%) of 22, and 10 (52.6%) of 19 mesotheliomas stained positively with 44-3A6 and SM3, respectively, whereas all 23 (100%) adenocarcinomas reacted with both antibodies. Sixteen (80%) of 20 mesotheliomas and 14 (63.6%) of 22 lung adenocarcinomas reacted with HBME-1, whereas 16 (80%) of 20 mesotheliomas and only three (11.1%) of 27 adenocarcinomas were positive for thrombomodulin. Because thrombomodulin was expressed in most mesotheliomas but in only a few lung adenocarcinomas, this marker may have some diagnostic value when it is included in the standard immunohistochemical panel of markers used in the evaluation of mesotheliomas, especially when a positive marker for mesothelioma is needed. Antibodies 44-3A6, SM3, and HBME-1 have no practical value in discriminating epithelial pleural mesothelioma from lung adenocarcinoma.