NEOPLASIA V.2011

8/3/2019 NEOPLASIA V.2011

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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=English


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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

NEOPLASIA V.2011

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