RESUMEN
Porphyria cutanea tarda (PCT), a liver disease with skin lesions caused by excess liver production of uroporphyrin (URO), is associated with consumption of alcoholic beverages or estrogens, and moderate iron overload. Recently, it has been shown that many PCT patients carry mutations in the HFE gene, which is responsible for hereditary hemochromatosis. Mice homozygous for either the null mutation in the Hfe gene or the C282Y missense mutation rapidly accumulate hepatic parenchymal iron similar to patients with hemochromatosis. Here we investigated whether disruption of the murine Hfe gene would result in hepatic uroporphyria. Mice homozygous for the Hfe-null mutation accumulated high levels of hepatic URO when fed 5-aminolevulinate (ALA). Hfe (+/-) mice also accumulated hepatic URO when fed ALA, but at a much slower rate. The amount of accumulated URO in the null mutant mice was similar to that in wild-type mice treated with iron carbonyl in the diet, or injected with iron dextran. Iron in both wild-type and Hfe (+/-) mice was mostly in Kupffer cells. In contrast, Hfe (-/-) mice had considerable parenchymal iron deposition as well, in a pattern similar to that observed in wild-type mice treated with iron carbonyl. URO accumulation was accompanied by 84% and 33% decreases in hepatic uroporphyrinogen decarboxylase activities in Hfe (-/-) and Hfe (+/-) mice, respectively. No increases in CYP1A2 or other cytochrome P450s were detected in the Hfe-null mutant mice. We conclude that this experimental model of uroporphyria is a valid model for further investigations into the mechanism of PCT.
Asunto(s)
Ácido Aminolevulínico , Hemocromatosis/genética , Hierro/fisiología , Mutación/fisiología , Porfiria Cutánea Tardía/genética , Uroporfirinas/metabolismo , Ácido Aminolevulínico/farmacología , Animales , Citocromo P-450 CYP1A2/metabolismo , Modelos Animales de Enfermedad , Hierro/metabolismo , Compuestos de Hierro Carbonilo , Complejo Hierro-Dextran/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones , Compuestos Organometálicos/farmacología , Porfiria Cutánea Tardía/metabolismo , Valores de Referencia , Uroporfirinógeno Descarboxilasa/metabolismoRESUMEN
CYP2E1 has been reported to have an essential role in alcohol-mediated increases in hepatic steatosis and acetaminophen hepatotoxicity. We found that pretreatment of Cyp2e1(-/-) mice with ethanol plus isopentanol, the predominant alcohols in alcoholic beverages, for 7 days resulted in micro- and macrovesicular steatosis in the livers of all mice, as well as a dramatic increase in acetaminophen hepatotoxicity. In Cyp2e1(-/-) mice administered up to 600 mg acetaminophen/kg alone and euthanized 7 h later, there was no increase in serum levels of ALT. In Cyp2e1(-/-) mice pretreated with ethanol and isopentanol, subsequent exposure to 400 or 600 mg acetaminophen/kg resulted in centrilobular necrosis in all mice with maximal elevation in serum levels of ALT. Acetaminophen-mediated liver damage was similar in males and females. Hepatic microsomal levels of APAP activation in untreated females were similar to those in males treated with the alcohols. However, the females, like the males, required pretreatment with the alcohols in order to increase APAP hepatotoxicity. These findings suggest that, in the Cyp2e1(-/-) mice, the alcohol-mediated increase in acetaminophen hepatotoxicity involves the contribution of other factors, in addition to induction of CYP(s) that activate acetaminophen. Alternatively, CYP-mediated activation of acetaminophen measured in vitro may not reflect the actual activity in vivo. Our findings that a 7-day treatment with ethanol and isopentanol causes extensive hepatic steatosis and increases acetaminophen hepatotoxicity in Cyp2e(-/-) mice indicate that CYP2E1 is not essential for either response.
Asunto(s)
Acetaminofén/toxicidad , Analgésicos no Narcóticos/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas , Citocromo P-450 CYP2E1/metabolismo , Etanol/toxicidad , Hígado Graso Alcohólico/etiología , Pentanoles/toxicidad , Acetaminofén/farmacocinética , Analgésicos no Narcóticos/farmacocinética , Animales , Benzoquinonas/metabolismo , Biotransformación/efectos de los fármacos , Citocromo P-450 CYP2E1/genética , Sinergismo Farmacológico , Hígado Graso Alcohólico/enzimología , Femenino , Iminas/metabolismo , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/patología , Hepatopatías/enzimología , Masculino , Ratones , Ratones Endogámicos C57BL , Factores SexualesRESUMEN
Ethanol and isopentanol are the predominant alcohols in alcoholic beverages. We have reported previously that pretreatment of rats with a liquid diet containing 6.3% ethanol plus 0.5% isopentanol for 7 days results in a synergistic increase in acetaminophen hepatotoxicity, compared with rats treated with either alcohol alone. Here, we investigated the role of CYP3A in acetaminophen hepatotoxicity associated with the combined alcohol treatment. Triacetyloleandomycin, a specific inhibitor of CYP3A, protected rats pretreated with ethanol along with isopentanol from acetaminophen hepatotoxicity. At both 0.25 and 0.5 g acetaminophen/kg, triacetyloleandomycin partially prevented elevations in serum levels of alanine aminotransferase. At 0.25 g acetaminophen/kg, triacetyloleandomycin completely protected 6 of 8 rats from histologically observed liver damage, and partially protected the remaining 2 rats. At 0.5 g acetaminophen/kg, triacetyloleandomycin decreased histologically observed liver damage in 7 of 15 rats. In rats pretreated with ethanol plus isopentanol, CYP3A, measured immunohistochemically, was decreased by acetaminophen treatment. This effect was prevented by triacetyloleandomycin. These results suggest that CYP3A has a major role in acetaminophen hepatotoxicity in animals administered the combined alcohol treatment. We also found that exposure to ethanol along with 0.1% isopentanol for only 3 days resulted in maximal increases in acetaminophen hepatotoxicity by the combined alcohol treatment, suggesting that short-term consumption of alcoholic beverages rich in isopentanol may be a risk for developing liver damage from acetaminophen.
Asunto(s)
Acetaminofén/toxicidad , Hidrocarburo de Aril Hidroxilasas , Enfermedad Hepática Inducida por Sustancias y Drogas , Etanol/farmacología , Pentanoles/farmacología , Troleandomicina/farmacología , Analgésicos no Narcóticos/toxicidad , Animales , Citocromo P-450 CYP3A , Inhibidores Enzimáticos del Citocromo P-450 , Sistema Enzimático del Citocromo P-450/metabolismo , Interacciones Farmacológicas , Etanol/administración & dosificación , Hepatopatías/enzimología , Hepatopatías/patología , Hepatopatías/prevención & control , Masculino , Oxidorreductasas N-Desmetilantes/antagonistas & inhibidores , Oxidorreductasas N-Desmetilantes/metabolismo , Pentanoles/administración & dosificación , Sustancias Protectoras/farmacología , Ratas , Ratas Endogámicas F344RESUMEN
Previous work has implicated CYP1A2 in experimental uroporphyria caused by polyhalogenated aromatic compounds, and in uroporphyria caused by iron and 5-aminolevulinate (ALA) in the absence of inducers of CYP1A2. Here we examined whether the different susceptibilities of SWR and C57BL/6 strains of mice to uroporphyria in the absence of inducers of CYP1A2 are related to different levels of CYP1A2. Enzymological assays (ethoxy- and methoxyresorufin dealkylases, and uroporphyrinogen oxidation) and immunoblots indicated that there was about twice the amount of hepatic CYP1A2 in SWR mice compared with C57BL/6 mice. Immunohistochemistry revealed that CYP1A2 was located centrilobularly in the liver, and the staining was more intense in SWR mice than in C57BL/6 mice. Hepatic non-heme iron was about double in SWR compared with C57BL/6 mice. In SWR mice given iron dextran, hepatic iron was 1.7-fold that of C57BL/6 mice given iron dextran. SWR mice administered ALA in the drinking water accumulated much less hepatic protoporphyrin than did C57BL/6 mice. To confirm the importance of small increases in CYP1A2, C57BL/6 mice were given a low dose of 3-methylcholanthrene (MC) (15 mg/kg), as well as iron and ALA. There was about a 5- to 6-fold increase in hepatic uroporphyrin accumulation after 32 days on ALA compared with animals not given MC. In these animals, CYP1A2 was increased by 10-fold at 2 days, but returned to basal levels by 14 days. We conclude that small and transient differences in CYP1A2 may be important in the development of uroporphyria.
Asunto(s)
Ácido Aminolevulínico/farmacología , Citocromo P-450 CYP1A2/metabolismo , Hierro/farmacología , Hígado/enzimología , Uroporfirinas/orina , Animales , Citocromo P-450 CYP1A2/análisis , Inmunohistoquímica , Hígado/efectos de los fármacos , Hígado/patología , Ratones , Ratones Endogámicos C57BL , Especificidad de la Especie , Uroporfirinas/metabolismoRESUMEN
History of the concept and definition of hepatitis is briefly reviewed. The landmarks of progress are based on better understanding of liver structure and introduction of biopsy techniques to follow the pathologic alterations in acute and chronic hepatitis, cirrhosis, dysplasia and hepatoma. Modern achievements are recognition of the etiologic agents of viral hepatitis A through G, viral nucleic acid sequencing, viral genome and gene products leading to development of immunologic tests to etiologic diagnosis. Viral particles are visualized by electron microscopy. In tissue, localization of viral products is obtained by histochemical, immunologic and by in situ hybridization methods. Diagnostic criteria for each of the viral etiologic agents is reviewed, as is cirrhosis and its occurrence in viral hepatitis and alcohol abuse.
Asunto(s)
Hepatitis/historia , Cirrosis Hepática/historia , Hepatitis/diagnóstico , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/historia , Hepatitis Viral Humana/diagnóstico , Hepatitis Viral Humana/historia , Historia del Siglo XVII , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Historia Antigua , Humanos , Cirrosis Hepática/diagnósticoRESUMEN
Novel thiazolidine prodrugs were prepared by the condensation of L-cysteine with aldose disaccharides. Using a disaccharide in prodrug construction allows for a terminal cyclic sugar moiety to be present on the prodrug, which may allow the delivery of the agent to specific receptors, such as the asialoglycoprotein receptor (ASGPR) of hepatocytes, that require specific structural motifs for recognition. Three L-cysteine prodrugs were synthesized with a pendant cyclic galactose moiety; two related glucose-bearing prodrugs were synthesized for comparison. The prodrugs were designed to release L-cysteine, which is then available to support glutathione (GSH) biosynthesis and provide cytoprotection against a variety of toxic insults. Protection studies in Swiss-Webster mice used acetaminophen (575 mg/kg), a well-documented hepatotoxin which depletes GSH at overdose. Three prodrugs performed exceptionally well against acetaminophen-induced hepatotoxicity, as measured by increased survival and improved histological profiles of liver tissue after 48 h. In further experimentation, two of the disaccharide-based prodrugs, prepared from alpha- and beta-lactose, were compared with the monosaccharide-based compound prepared from ribose. Co-administration of the selected prodrugs with a 400 mg/kg dose of acetaminophen to Swiss-Webster mice prevented the short-term depletion in hepatic GSH and also reduced hepatotoxicity as determined by histological damage and serum levels of alanine aminotransferase. A single dose of the prodrugs alone had no effect on hepatic drug metabolizing enzymes [glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase (QOR), UDP-glucuronosyltransferase (UGT), and cytochrome P450], but, concordant with the reduction of hepatotoxicity, the latentiated forms prevented the significant elevation in QOR activity and mRNA and GST mRNA elicited by acetaminophen itself. GST activity, UGT activity and mRNA, and cytochrome P450 concentration were all unaffected by acetaminophen or the prodrugs. These studies identified novel L-cysteine prodrugs with potentially useful hepatoprotective activity. However, no structure-activity relationships were obvious. In addition, the occurrence of targeted delivery to hepatocytes remains ambiguous.
Asunto(s)
Acetaminofén/antagonistas & inhibidores , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Cisteína/análogos & derivados , Cisteína/farmacología , Acetaminofén/toxicidad , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Disacáridos/química , Glutatión/metabolismo , Ratones , Profármacos/química , Quinona Reductasas/metabolismo , ARN Mensajero/biosíntesisRESUMEN
New Hampshire and Vermont currently have two rabies epizootics occurring in raccoon and fox populations. These are continuations of the established raccoon strain which has been migrating northward from the mid-Atlantic and the fox strain which is migrating south and eastward from Canada and New York. These started in the early 1990s, and the wild animal cases have increased from 0 to 1 case per year in Vermont in the late 1980s to 179 in 1995, and from 0 to 4 cases in New Hampshire to 152 in 1995. Since 1992 there has been a slight increase in domestic animal cases, but no human cases have been reported. The cost of prophylaxis and animal testing has greatly increased, including one episode where 665 persons were exposed to a rabid kitten and underwent postexposure prophylaxis at an estimated cost of $1.5 million. This paper gives epidemiologic data for the two states and reviews the current literature to discuss history, clinical features, testing, postexposure prophylaxis, and treatment of rabies.
Asunto(s)
Zorros , Rabia/epidemiología , Rabia/veterinaria , Mapaches , Animales , New Hampshire , Rabia/diagnóstico , Rabia/economía , Rabia/prevención & control , Rabia/terapia , VermontRESUMEN
CYP2E is considered the only form of cytochrome P450 responsible for ethanol-mediated increases in acetaminophen hepatotoxicity. However, in experimental systems used for investigating ethanol-mediated increases in acetaminophen hepatotoxicity, animals are withdrawn from ethanol for 16 to 24 hr before the administration of acetaminophen to ensure the clearance of ethanol from the circulation. In rats, CYP2E has been shown to decrease to control levels after this time period of withdrawal from ethanol. We have previously shown in cultured human and rat hepatocytes, and in intact rats, that ethanol induces CYP3A in addition to CYP2E. To determine if there might be a role for CYP3A in ethanol-mediated APAP hepatotoxicity in addition to the recognized role for CYP2E, we investigated the effect of triacetyloleandomycin (TAO) on acetaminophen hepatotoxicity in ethanol-pretreated rats, as well as the effect of 11 hr withdrawal from ethanol on hepatic levels of CYP3A and CYP2E. TAO was dissolved in saline instead of dimethylsulfoxide, the solvent most usually employed, since dimethylsulfoxide inhibits CYP2E. Rats were administered 6.3% ethanol as part of the Lieber-DeCarli diet for 7 days, followed by replacement of the liquid diet with water for 11 hr. This 11-hr withdrawal from ethanol resulted in a decrease in hepatic levels of ethanol-induced CYP2E; however, considerable induction was still evident. There was no significant decrease in CYP3A. TAO completely prevented the histologically observed liver damage from acetaminophen in ethanol-pretreated rats, but did not prevent the increase in serum levels of AST. In ethanol-pretreated rats, exposure to APAP in the absence of TAO was associated with a 75% decrease in CYP3A, compared to animals exposed to APAP in the presence of TAO. These results suggest that CYP3A may have been suicidally inactivated by acetaminophen in the absence of TAO. Our findings suggest that CYP3A has a major role in ethanol-mediated increases in acetaminophen hepatotoxicity.
Asunto(s)
Acetaminofén/toxicidad , Analgésicos no Narcóticos/toxicidad , Hidrocarburo de Aril Hidroxilasas , Depresores del Sistema Nervioso Central/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Citocromo P-450 CYP2E1/biosíntesis , Sistema Enzimático del Citocromo P-450/biosíntesis , Etanol/farmacología , Hígado/enzimología , Oxidorreductasas N-Desmetilantes/biosíntesis , Animales , Antibacterianos/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citocromo P-450 CYP3A , Inhibidores Enzimáticos del Citocromo P-450 , Esquema de Medicación , Interacciones Farmacológicas , Inducción Enzimática/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Oxidorreductasas N-Desmetilantes/antagonistas & inhibidores , Ratas , Ratas Endogámicas F344 , Troleandomicina/farmacologíaRESUMEN
Cytochrome P450 2E (CYP2E) is considered responsible for ethanol-mediated increases in acetaminophen (APAP) hepatotoxicity. However, it has been shown in cultured human and rat hepatocytes and intact rats that ethanol induces CYP3A in addition to CYP2E. Therefore, an investigation was made in rats to see whether or not an inhibitor of CYP3A, triacetyloleandomycin (TAO), would protect against ethanol-mediated increases in APAP hepatotoxicity. Rats, treated with 6.3 percent ethanol in the Lieber-DeCarli diet for 7 days, were administered APAP (lg/kg, i.g.) 11 hrs after removal of the diet. Triacetyloleandomycin (500 mg/kg, saline solution) was injected i.p. 2 hrs before the administration of APAP. In rats pretreated with ethanol, treatment with APAP for 7 hrs resulted in focal centrilobular congestion and steatosis. Triacetyloleandomycin completely prevented the histological liver damage in all 8 animals. These results suggest that, in ethanol-treated rats, CYP3A plays a major role in increasing APAP hepatotoxicity.
Asunto(s)
Acetaminofén/toxicidad , Hidrocarburo de Aril Hidroxilasas , Inhibidores Enzimáticos del Citocromo P-450 , Etanol/farmacología , Hígado/metabolismo , Oxidorreductasas N-Desmetilantes/antagonistas & inhibidores , Troleandomicina/farmacología , Animales , Citocromo P-450 CYP3A , Sistema Enzimático del Citocromo P-450/metabolismo , Inhibidores Enzimáticos/farmacología , Histocitoquímica , Hígado/citología , Hígado/lesiones , Masculino , Oxidorreductasas N-Desmetilantes/metabolismo , Ratas , Ratas Endogámicas F344RESUMEN
It is now possible to detect low copy numbers of messenger ribonucleic acid (mRNA) while retaining good histologic morphology for the determination of specific gene expression in diseased tissues. This technology will allow the pathologist to provide important prognostic information about tumors (expression of oncogenes and growth factors), to identify the subclones within the tumor which may be most likely to metastasize (expression of adhesion molecules and proteases) and to identify etiologic genetic aberrations (viral insertions). A technique for in-situ hybridization to mRNA has been developed for use in formalin fixed paraffin embedded tissues which is suitable for a hospital histology laboratory. Optimal conditions for the procedure were determined by using a biotinylated poly (d)T oligonucleotide probe. Results were dependent on the tissue type, fixation time, condition of the tissue prior to fixation, and degree of digestion before hybridization. The temperature and conditions of hybridization were optimized so that the poly d(T) control probe and the longer test probe could be run simultaneously. Streptavidin and avidin alkaline phosphatase detection systems were tested using levamisole to minimize background staining, and a biotin blocking agent to reduce reaction to renal tubular biotin. Increasing the temperature of stringency washes did not significantly improve the specificity but had a markedly detrimental effect on tissue morphology. The mRNA appears to remain stable within routinely fixed surgical material over long periods of time allowing for large retrospective studies. A review of c-erbB-2 expression in 16 human breast lesions was carried out comparing mRNA in-situ hybridization to immunoperoxidase and cytosolic methods. By direct localization of both message and antigen, it was possible to demonstrate focal positivity that cytosolic methods did not detect. Aberrant translation was noted in one case, and c-erbB-2 expression in non-malignant breast was detected in two cases.
Asunto(s)
Biotina , Hibridación in Situ/métodos , Sondas de Oligonucleótidos , ARN Mensajero/metabolismo , Animales , Neoplasias de la Mama/metabolismo , Citosol/metabolismo , Enfermedad Fibroquística de la Mama/metabolismo , Genes erbB-2 , Técnicas para Inmunoenzimas , Ratas , Ratas Endogámicas F344 , Coloración y EtiquetadoRESUMEN
Fifty-two human breast tumors were screened for the presence of DNA homology to mouse mammary tumor virus (MMTV) using molecularly cloned MMTV proviral genomic DNA probes and dot-blot hybridization. Seven patients were found to contain an entire provirus (gag, pol, env, and LTR positive at high stringency). Fifty percent (5/10) of patients having a first degree relative with breast carcinoma were found to have DNA homology to the gag-pol portion of the MMTV genome when hybridization and washing was performed at moderate (56C) stringency. Thirty-nine percent (7/18) of patients with any positive family history and 23 percent (8/34) of patients with a negative family history demonstrated homology under these parameters. Of the patients positive for gag-pol at moderate stringency, fewer had taken exogenous hormones than the sample group (20 percent vs 52 percent), more were parous (93 percent vs 68 percent), estrogen receptor positive (69 percent vs 48 percent), and male (13 percent vs 4 percent). At higher stringency (62C) no correlation to family history, hormone use or sex was detected, but positivity was noted among estrogen and progesterone receptor positive patients (67 percent vs 48 percent). Under lower stringency wash conditions, mismatched MMTV-related sequences are identified suggesting the existence of an endogenous gene with partial homology to MMTV. High stringency hybridization may identify a related retrovirus with significant homology to MMTV.
Asunto(s)
Neoplasias de la Mama/genética , ADN de Neoplasias/análisis , ADN Viral/análisis , Genoma Viral , Virus del Tumor Mamario del Ratón/genética , Homología de Secuencia de Ácido Nucleico , Adulto , Anciano , Anciano de 80 o más Años , Animales , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Estrógenos/farmacología , Femenino , Genes gag , Genes pol , Humanos , Masculino , Virus del Tumor Mamario del Ratón/ultraestructura , Ratones , Ratones Endogámicos C3H , Persona de Mediana Edad , Progesterona/farmacología , Provirus/genética , Estándares de Referencia , Factores SexualesRESUMEN
The involvement of the liver by malignancy, whether it be primary or metastatic, carries a grave prognosis. At this time, chemotherapy is solely palliative, and no survival advantage has been established. Resection of metastatic or primary carcinoma of the liver in a select number of patients may provide a survival advantage and an occasional cure. However, studies are difficult to control, and claims of survival benefits have been based on historical data of untreated disease prior to 1978. Currently, clinical trials are underway combining modes of therapy in the hope of increasing patient survival. Reduction of operative mortality to below five percent for liver resection is attributable to a major advance in operative technique. Other advances are improved diagnostic techniques for detection of liver metastases and selection of patients for resection. Finally, newer strategies for chemotherapy made practicable continuous infusion by implantable or external pumps, redoubling response rates to fluorodeoxyuridine (FUDR) in regional and 5-fluorouracil (5-FU) in systemic chemotherapy. A review of the current literature is presented along with data accumulated over the three-year experience of the Moffitt Cancer Center, Tampa, Florida. The case material from Moffitt Cancer Center is included to illustrate progress and limitations of combined surgical, regional, and systemic chemotherapy for primary and metastatic liver cancers.
Asunto(s)
Adenocarcinoma/terapia , Neoplasias Hepáticas/terapia , Melanoma/terapia , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Terapia Combinada , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Melanoma/tratamiento farmacológico , Melanoma/secundario , Melanoma/cirugía , PerfusiónRESUMEN
Approximately 1,000 assays for estrogen receptor (ER) in primary human breast tumors have been performed at St. Joseph's Hospital over a period of seven years; 700 of these included assays for progesterone receptor (PR). Based on the method of analysis (dextran-coated charcoal) and criteria for a positive result used for this survey, 80 percent of the primary tumors were ER-positive and 56 percent were PR-positive. In those cases where both assays were performed, 47.4 percent were ER-positive, PR-positive; 19.8 percent were ER-positive, PR-negative; 6.2 percent were ER-negative, PR-positive; and 26.6 percent were ER-negative, PR-negative. The mean concentration of ER increased with the advancing age of the patient; essentially the same relationship was observed for PR. The concentration of ER and PR was not directly dependent upon the degree of cellularity of the tumor. Lobular carcinoma and the mixed types containing ductal and lobular elements had the highest frequency of being positive for both steroid receptors, while medullary and papillary carcinomas were lowest. Three hundred and twenty-two cases had follow-up studies and were examined on the basis of the available information in the files of St. Joseph's Hospital Tumor Registry. A higher survival rate in patients with both ER and PR positivity became evident. In a community hospital setting, our data confirm the usefulness of estrogen and progesterone receptor assays in decisions of clinical management and considerations of prognosis in patients with mammary carcinoma.