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NEOPLASIA V&
ENVIROMENTAL DISEASES
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Host Defense Against Tumor
Immune surveillance
a normal function of the immune system(emerging malignant cells)
idea supported by many observations-lymphocytic infiltrates around tumors-increased incidence of some cancers in
immunodeficient individuals immune
Surveillance is imperfect and often cannotcontrol rapidly growing tumors
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Immune surveillance
Immune surveillance
also the effect of the immune system in
selecting for tumor variants.
These variants have reduced
immunogenicity
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TUMOR ANTIGENS
Classified into two categories based on theirpatterns of expression:
1.-tumor-specific antigens,which are
present only on tumor cells and not on anynormal cells.
2.-tumor-associated antigens, which arepresent on tumor cells and also on somenormal cells.
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TUMOR ANTIGENS
Cytotoxic T lymphocytes (CTLs,CD8+)are the major immune defense
mechanism against tumors.
Recognize peptides bound to class I
major histocompatibility complex(MHC) molecules
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The modern classification of tumor antigens isbased on their molecular structure and source
1.-Products of Mutated Genes
Oncogenes: RAS mutated, Bcr/Abl Tumor Suppressor Genes: p53 mutated2.-Overexpressed or Aberrantly
Expressed Cellular Proteins:
Tyrosinase, an enzyme involved in
melanin biosynthesis that is expressedonly in normal melanocytes andmelanomas
Melanoma antigen (MAGE) genes
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classification of tumor antigens
3.-Tumor Antigens Produced by Oncogenic Viruses:Human papilloma virus E6 &E7 proteins in cervicalcancer. EBNA proteins in EBV Lymphoma
4.-Oncofetal Antigens.
Carcinoembryonic antigen (CEA)alpha-fetoprotein (AFP). (Tumor Markers)5.-Cell Type-Specific Differentiation Antigens.
lymphomas may be diagnosed as B cell-derived tumors
by the detection of surface markers characteristic of thislineage, such as CD10 (previously called common acutelymphoblastic leukemia antigen, or CALLA) and CD20
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ANTITUMOR EFFECTORMECHANISMS
Cytotoxic T lymphocytes
Natural killer cells
Macrophages Antibodies
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Mechanisms by which tumorsevade the immune system.
Selective outgrowth of antigen-negative variants: Lack of costimulation (costimulatory molecule
B7-1)
Immunosuppression: Tumors or tumor productsmay also be immunosuppressive. For example,TGF-
Antigen masking (glycocalyx molecules)
Apoptosis of cytotoxic T cells: Some melanomasand hepatocellular carcinomas express Fasligand
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DIAGNOSTICO DELABORATORIO DEL CANCERMarcadores tumorales bioqumicos
(suero, orina heces)
Mtodos morfolgicosFrotis citolgico
Biopsia por aspiracin con aguja delgada
(forma de frotis citolgico)
Biopsia tisular con aguja gruesa o incisional (tincin HE yespeciales)
Inmunohistoqumica
Citometra de flujo
Diagnstico molecular
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MARCADORES TUMORALESMARCADORES TUMORALESBIOQUIMICOSBIOQUIMICOS
HORMONASHORMONAS ANTGENOS ONCOFETALESANTGENOS ONCOFETALES PROTENAS ESPECFICAS (Igs, Ag prostPROTENAS ESPECFICAS (Igs, Ag prost
especfico)especfico) CARBOHIDRATOS (CA-19-9 CaCARBOHIDRATOS (CA-19-9 Ca
pncreas)pncreas)
MUCINAS Y GLUCOPROTENAS (CA-MUCINAS Y GLUCOPROTENAS (CA-125 Ca ovario,)125 Ca ovario,)
NUEVOS MARCADORES (p53 y RASNUEVOS MARCADORES (p53 y RAS
mutante en suero, orina, heces etc. )mutante en suero, orina, heces etc. )
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Hormonas
Gonadotrofina corinica humana
Epitelio placentario
Mola hidatidiformeCoriocarcinoma
CatecolaminasFeocromocitoma (mdula suprarrenal)
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Antgenos oncofetalesAntgenos oncofetales
Antgeno carcinoembrionarioAntgeno carcinoembrionario ACE CEAACE CEA
GLUCOPROTENAGLUCOPROTENA
TEJIDO EMBRIONARIO DE INTESTINOTEJIDO EMBRIONARIO DE INTESTINOPNCREAS HGADOPNCREAS HGADO
CANCERRES COLORRECTALES, DECANCERRES COLORRECTALES, DEPNCREAS Y GSTRICOSPNCREAS Y GSTRICOS
PATOLOGA NO NEOPLSICAPATOLOGA NO NEOPLSICA
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Antgenos oncofetalesAntgenos oncofetales
Alfa feto-protenaAlfa feto-protena
GLUCOPROTENAGLUCOPROTENA Normalmente en SACO EMBRIONARIONormalmente en SACO EMBRIONARIO CA HGADO Y CLULAS GERMINALESCA HGADO Y CLULAS GERMINALES
TESTICULARESTESTICULARES CA COLON, PULMN ,PANCREAS Y CACA COLON, PULMN ,PANCREAS Y CA
HEPATOCELULARES.HEPATOCELULARES. NO NEOPLSICASNO NEOPLSICAS
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Carcinoma Lymphoma Melanoma Sarcoma
Pankeratain + - - -
Leu Comm
Antigen(LCA)- + - -
Prot S/199HMB/45
- - + -
Desmin - - - +
Vimentin - - + +
Immunohistochemistry algorithm forpoorly differentiated tumores
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BIOLOGIA MOLECULARPATOLOGIA DIAGNOSTICA
MOLECULARPCR
RT-PCRHibridacin in situ
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PATOLOGIA DIAGNOSTICAMOLECULAR
El material para el PCR y sus variantes sepuede obtener de los tejidos conservadosen el Servicio de Patologa, ya sea en
formol o de los bloques de parafina
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HIBRIDACION IN SITU (ISH)
La hibridacin in situ es la tcnica molecularms usada en la patologa diagnstica
2 variantes
1.- Fluorescencia
2.- Cromgenos
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FISH
Sondas de oligonucleticos marcadas confluorescencia
3 tipos generales
1.- Cromosoma entero
2.- Sondas centromricas ( enumeran
copias de cromosoma especfico)3.- Sondas de alelos especficos
(gene supresor tumoral p53 o el oncogen
HER2/neu )
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Aplicaciones FISH
1.- Diagnstico, pronstico y monitoreo deneoplasias hematolgicas (leucemias ylinfomas)
2.- Pruebas para blanco teraputico
Ej: HER2/neu (del oncogen del receptordel factor de crecimiento epidrmicohumano del cncer de mama)
Fluorescence in situ hybridization analysis for
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Fluorescence in situ hybridization analysis for
BCR-ABL
chromosomal translocations. (Chronic myeloid
leukemia)
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HER2 FISH signal is red orange
and CEN 17 FISH signal is green in the blue
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Brightfield in situ hybridization and dual color fluorescence in situhybridization (FISH) for HER2 and CEN 17.
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ENVIRONMENTAL
DISEASES
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Environmental Pathology
The overall fatality rate for occupationalexposures is 4.8 per 100,000 workers; thehighest rates occur in the mining,
agricultural, construction, transportation,and public utility industries.
In addition it may lead to premature
death . The magnitude of occupationaldiseases is most likely underestimated
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Reported Occupational Diseases inthe United States in 1997
Repeated trauma
Skin disorders
Lung conditions due to toxic exposures Physical injury
Poisoning
Lung disease due to dusts
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Organ-Specific Carcinogens in
Tobacco Smoke
Organ Lung, larynx Esophagus Pancreas Bladder Oral cavity (smoking) Oral cavity (snuff)
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Deaths Attributable to Cigarette Smoking in the
United States
Cancer
Cardiovascular disease
Respiratory disease Residential fires
Perinatal deaths
Lung cancer and heart diseaseattributable to passive smoking
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Alcohol Abuse
Liver (Fatty change,Acute hepatitis Alcoholiccirrhosis)
Central Nervous system (S. de Wernicke y de
Korsakoff) Peripheral neuropathy
Cardiovascular system (Cardiomyopathy)
Hypertension Vasopressor Gastrointestinal tract (Gastritis)
Pancreatitis
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Alcohol Abuse
Skeletal muscle ( Rhabdomyolysis)
Reproductive system (Testicular atrophy,
Spontaneous abortion)
Fetal alcohol syndrome (Growth retardation,Mental retardation, Birth defects )
Cancer ( oral cavity, pharynx, esophagus, liver,and possibly the breast )
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Alcohol Abuse
One of its metabolites, acetaldehyde, may act asa tumorpromoter
Ethanol inhibits the detoxification of chemical
carcinogens such as nitrosamines, which havebeen associated with tumors of the uppergastrointestinal tract.
Heavy alcohol use synergizes with chronic
hepatitis B or C infection in predisposing to thedevelopment of hepatocellular carcinoma
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Obesity and cancer
In 2001, experts concluded that cancers ofthe colon, breast (postmenopausal),endometrium, kidney, and esophagus
are associated with obesity. Some studieshave also reported links between obesityand cancers of the gallbladder, ovaries,
andpancreas.
http://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=gallbladder&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=pancreas&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=pancreas&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=gallbladder&version=Patient&language=English8/3/2019 NEOPLASIA V.2011
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Combined use interacts in amultiplicative way on cancer risk.
Alcohol drinking and smoking areindependent risk factors forupperaerodigestive tract cancers.
Convincing evidence that acetaldehyde,the first metabolite of ethanol and aconstituent of tobacco smoke, is a local
carcinogen in humans. Int J Cancer.2004 Sep 10;111(4):480-3