Pre-Cancerous Pre-Cancerous Lesions: Red Flags Lesions: Red Flags for future Cancers for future Cancers

Gerardo H. Cornelio.MD, FPCP, Gerardo H. Cornelio.MD, FPCP, FPSMO, FPSOFPSMO, FPSO

Magnitude of Cancer Magnitude of Cancer ProblemProblem

in the Philippinesin the PhilippinesINCIDENCEINCIDENCE 3rd in incidence after communicable & 3rd in incidence after communicable &

cardiovascular diseasescardiovascular diseases 1 out of 1,000 Filipinos has cancer1 out of 1,000 Filipinos has cancer 114:103 Females to Males, Filipino114:103 Females to Males, Filipino Incidence rates increase w/ Age:Incidence rates increase w/ Age:

0-14 yr.: 3.6% of cancers0-14 yr.: 3.6% of cancers >35 yr.: 91% of cancers>35 yr.: 91% of cancers >=50 yr.: 76% of cancers>=50 yr.: 76% of cancers

THE TEN LEADING CANCER THE TEN LEADING CANCER SITES IN THE PHILIPPINESSITES IN THE PHILIPPINES

0.00%

2.00%

4.00%

6.00%

8.00%

10.00%

12.00%

14.00%

16.00% LungBreastLiverCervix LeukemiasColonThyroidStomachNasopharynxLymphomas

Philippine Cancer Facts and Estimates, 1998

ESTIMATED LEADING ESTIMATED LEADING CAUSES OF CANCER CAUSES OF CANCER

DEATHSDEATHS

01,0002,0003,0004,0005,0006,0007,0008,0009,000

10,000

# OF CASES

CANCER SITES

LUNG

LIVER

BREAST

CERVIX

COLON

STOMACH

PANCREAS

PROSTATE

RECTUM

Philippine Cancer Facts and Estimates, 1998

TEN LEADING CANCER SITES TEN LEADING CANCER SITES IN MALES IN MALES

LUNG(1)

LIVER(2)

ORAL(10)

RECTUM(9)

LYMPHOMA (8)

NASOPAHRYNX(7)

STOMACH(6)

COLON(5)

LEUKEMIA(4)

PROSTATE (3)

Philippine Cancer Facts and Estimates, 1998

TEN LEADING CANCER SITES TEN LEADING CANCER SITES IN WOMEN IN WOMEN

BREAST(1)

UTERUS(10)STOMACH(9)

LIVER(8)

COLON(7) LEUKEMIAS(6)

OVARY(5)

THYROID(4)

LUNG(3)

CERVIX(2)

Philippine Cancer Facts and Estimates, 1998

What are the Top TenWhat are the Top Ten Cancers in the Philippines? Cancers in the Philippines?Male Female Child

Lung Breast Leukemia (ALL)

Liver Cervix Lymphoma (NHL)

Stomach Lung Brain/ Spinal (Medullablastoma;Astrocytoma)

Colon Ovary Retinoblastoma

Rectum Stomach Bone (Osteosarcoma)

NasopharynxLeukemiaOral cavityPancreas

NHL

LiverThyroid

Oral cavityColon

Rectum

STS (Rhabdo-myosarcoma)Kidney (Wilm’s)Gonadal GCTEpithelioma

CANCERCANCER

MANAGEMENT

Environment

Genetics

Clinical Manifestations

Metastasis

Anaplasia

Proliferation

DIAGNOSISBiopsy

StagingPreventive

Curative

Supportive

THE NINE WARNING THE NINE WARNING SIGNSSIGNS

C

A

U

T

I

O

N

U

S

•Change in bowel or bladder habits.

•A sore that does not heal.

•Unusual bleeding or discharge.

•Thickening of a lump in breast or elsewhere.

•Indigestion or difficulty in swallowing.

•Obvious change in a wart or mole.

•Nagging cough or hoarseness.

•Unexplained anemia.

•Sudden, unexplained weight loss.

What is Cancer?What is Cancer?

CANCER CELLS AND CANCER CELLS AND NORMAL CELLSNORMAL CELLS

CANCER CELLS AND CANCER CELLS AND NORMAL CELLSNORMAL CELLS

CANCER CELLSCANCER CELLS NORMAL CELLSNORMAL CELLS

Loss of contact inhibitionLoss of contact inhibition

Increase in growth factor secretionIncrease in growth factor secretion

Increase in oncogene expressionIncrease in oncogene expression

Loss of tumor suppressor genesLoss of tumor suppressor genes

Oncogene expression is rareOncogene expression is rare

Intermittent or co-ordinatedIntermittent or co-ordinatedgrowth factor secretiongrowth factor secretion

Presence of tumor suppressorPresence of tumor suppressorgenesgenes

NormalNormalcellcell

FewFewmitosesmitoses

FrequentFrequentmitosesmitoses

NucleusNucleus

Blood vesselBlood vessel

AbnormalAbnormalheterogeneous cellsheterogeneous cells

Cancer GenesCancer Genes

Proto-oncogenesProto-oncogenes – normally promote – normally promote normal cell growth; mutations normal cell growth; mutations convert them to oncogenes.convert them to oncogenes.

Tumor suppressor genesTumor suppressor genes – normally – normally restrain cell growth; loss of function restrain cell growth; loss of function results in unregulated growth.results in unregulated growth.

DNA repair genesDNA repair genes – when faulty, – when faulty, result in an accumulated rate of result in an accumulated rate of mutations.mutations.

ONCOGENESONCOGENESONCOGENE FUNCTION ASSOCIATED HUMAN CANCER

SIS Platelet-derived growth factorERB1 Epidermal growth factorFMS CSF-1 receptorKIT Stem cell growth factor receptorMET Hepatic growth factor receptor Papillary renal cancerHER2/ NEU/ ERBB2 Heregulin receptor Cancer of breast, ovary, bladder; glioblastomaRET Neurotrophic growth receptor Medullary thyroid cancerTRKA Nerve growth factor receptorERBA Thyroid hormone receptor (nuclear)RAS (H,K,N) GTPase Cancer of lung, pancreas, bladder, colon, rectumBCR-ABL Cytoplasmic tyrosine kinase Chronic myelogenous leukemiaRAF Cytoplasmic tyrosine kinaseSRC Cytoplasmic tyrosine kinase

FOS Transcription factorJUN Transcription factorMYC (c,L,N) Transcription factor Burkitt’s lymphoma, neuroblastoma, lung

cancerBCL6 Transcription factor Large cell lymphomaBCL2 Anti-apoptosis Prostate cancer, lymphoma

Multistage Multistage CarcinogenesisCarcinogenesis

CARCINOGENSCARCINOGENS Occupation related causesOccupation related causes Lifestyle related causesLifestyle related causes

TobaccoTobacco DietDiet Sexual practicesSexual practices

Multifactorial causesMultifactorial causes Viral carcinogensViral carcinogens Chemical carcinogensChemical carcinogens Ionizing radiationIonizing radiation

Occupational Risk Occupational Risk FactorsFactors

EtiologyEtiologyArsenicArsenic

AsbestosAsbestos

BenzeneBenzene

BenzedineBenzedine

Chromium cpdsChromium cpds

Radiation (mining)Radiation (mining)

Mustard gasMustard gas

Polycyclic hydrocarbonsPolycyclic hydrocarbons

Vinyl ChlorideVinyl Chloride

Site of MalignancySite of MalignancyLung, skin, liverLung, skin, liver

Mesothelium, lungMesothelium, lung

LeukemiaLeukemia

BladderBladder

LungLung

Numerous locationsNumerous locations

LungLung

Lung, skinLung, skin

Angiosarcoma of liverAngiosarcoma of liver

Lifestyle Risk FactorsLifestyle Risk Factors

Tobacco-related:Tobacco-related: Lung cancerLung cancer Pancreatic cancerPancreatic cancer Bladder cancerBladder cancer Renal cancerRenal cancer Cervical cancerCervical cancer

Diet-Related Risk Diet-Related Risk FactorsFactors

NitratesNitrates

SaltSalt

Low vitamins A, C, ELow vitamins A, C, E

Low consumption of Low consumption of yellow-green yellow-green vegetablesvegetables

Gastric CancerGastric Cancer

Esophageal Esophageal CancerCancer

Diet-Related Risk Diet-Related Risk FactorsFactors

High fatHigh fat

Low fiberLow fiber

Low calciumLow calcium

High boiled or High boiled or fried foodsfried foods

Colon CancerColon Cancer

Pancreatic CancerPancreatic Cancer

Prostate CancerProstate Cancer

Breast CancerBreast Cancer

Uterine CancerUterine Cancer

MycotoxinsMycotoxins Liver CancerLiver Cancer

Sexual Practices Risk Sexual Practices Risk FactorsFactors

Cervical CancerCervical Cancer

Sexual promiscuitySexual promiscuity

Multiple partnersMultiple partners

Unsafe SexUnsafe Sex

Human Human PapillomavirusPapillomavirus

Multifactorial FactorsMultifactorial Factors

Tobacco + AlcoholTobacco + AlcoholOral Cavity CancerOral Cavity Cancer

Esophageal CancerEsophageal Cancer

Tobacco + AsbestosTobacco + Asbestos

Tobacco + miningTobacco + mining

Tobacco + uranium Tobacco + uranium + radium+ radium

Respiratory Respiratory Tract CancerTract Cancer

Lung CancerLung Cancer

Chemical Chemical CarcinogenesisCarcinogenesis

Chemical Chemical CarcinogenCarcinogen

Promoter(s)Promoter(s)

Initiator(s)Initiator(s)(electrophilic, mutagenic)(electrophilic, mutagenic)

Normal CellsNormal Cells

Inactive MetabolitesInactive Metabolites

Initiated CellsInitiated Cells

Tumor CellsTumor Cells

ClonesClones

Gross TumorsGross Tumors

Radiation CarcinogenesisRadiation Carcinogenesis

Radiation-induced mutation in the Radiation-induced mutation in the host cellhost cell

Transmits irreversible changes in Transmits irreversible changes in gene expression to cell progenygene expression to cell progeny

Sources of Potentially Sources of Potentially Carcinogenic RadiationCarcinogenic Radiation

SunlightSunlight Artificial sources of UV lightArtificial sources of UV light X-raysX-rays Radio-chemicalsRadio-chemicals Nuclear fissionNuclear fission

Viral CarcinogenesisViral Carcinogenesis Viral carcinogens are classified Viral carcinogens are classified

into RNA and DNA viruses.into RNA and DNA viruses.

Most RNA oncogenic viruses Most RNA oncogenic viruses belong to the family of belong to the family of retroviruses that contain retroviruses that contain reverse reverse transcriptasetranscriptase mediates mediates transfer of viral RNA into virus transfer of viral RNA into virus specific DNA. specific DNA.

Sequence of Disease Sequence of Disease ProgressionProgression

Leukoplakia / ErythroplakiaLeukoplakia / Erythroplakia

DysplasiaDysplasia

Carcinoma in situCarcinoma in situ

Invasive CarcinomaInvasive Carcinoma

Regional / Distant MetastasisRegional / Distant Metastasis

Lung Cancer ProfileLung Cancer ProfileSmoke: 25 or moreSmoke: 25 or more

15 – 2415 – 24

14 or lower14 or lower

+ 50+ 50

+ 25+ 25

+ 10+ 10

1 or more cigars the past year1 or more cigars the past year + 5+ 5

3 or more vegetables a day3 or more vegetables a day - 5- 5

Parent, brother or sister w lung cancerParent, brother or sister w lung cancer + 10+ 10

Lived with a smokerLived with a smoker + 5+ 5

Live near a large city for 10 yearsLive near a large city for 10 years + 5+ 5

Asbestos worker without protection 5-20 yrs/ >20Asbestos worker without protection 5-20 yrs/ >20 +25 /50+25 /50

Radon, Cadmium, aluminum, silica, sulfur 5-20 />20Radon, Cadmium, aluminum, silica, sulfur 5-20 />20 +10 / 25+10 / 25

Eats 3 or more servings of fruits per dayEats 3 or more servings of fruits per day - 5- 5

Risk ChartRisk ChartScoreScore Your risk is:Your risk is:

Less than 0Less than 0 Very much below averageVery much below average

0 - 60 - 6 Much below averageMuch below average

7 - 107 - 10 Below averageBelow average

11 - 1211 - 12 AverageAverage

13 - 2113 - 21 Above averageAbove average

22 - 5322 - 53 Much above averageMuch above average

54 or higher54 or higher Very much above averageVery much above average

Lung CancerLung Cancer

Bronchial intraepithelial lesionsBronchial intraepithelial lesions

Squamous metaplasia or dysplasia in Squamous metaplasia or dysplasia in former smokersformer smokers

Loss of retinoic acid receptor-B Loss of retinoic acid receptor-B expressionexpression

BREAST CANCERBREAST CANCERSigns and symptoms at Signs and symptoms at

presentationpresentation Mass or painMass or pain

in the axillain the axilla

Palpable massPalpable mass ThickeningThickening PainPain

Nipple dischargeNipple discharge Nipple retractionNipple retraction

Edema or erythemaEdema or erythema

of the skinof the skin

Non Invasive Breast Non Invasive Breast CancerCancer

Lobular Carcinoma in situ (LCIS)Lobular Carcinoma in situ (LCIS) PremalignantPremalignant 20% develop IBC over 15 years20% develop IBC over 15 years 30% bilateral30% bilateral Annual mammography / Tamoxifen risk Annual mammography / Tamoxifen risk

reduction (56%) – NSABP P1reduction (56%) – NSABP P1 Ductal Carcinoma in situ (DCIS)Ductal Carcinoma in situ (DCIS)

MalignantMalignant Recurs in 35% in 10-15 yrs if biopsy aloneRecurs in 35% in 10-15 yrs if biopsy alone >25% develop IBC>25% develop IBC

BREAST CANCERBREAST CANCERMammographyMammography

BREAST CANCERBREAST CANCERSigns and symptoms at Signs and symptoms at

presentationpresentation Mass or painMass or pain

in the axillain the axilla

Palpable massPalpable mass ThickeningThickening PainPain

Nipple dischargeNipple discharge Nipple retractionNipple retraction

Edema or erythemaEdema or erythema

of the skinof the skin

BREAST CANCERBREAST CANCERSigns and symptoms at Signs and symptoms at

presentationpresentation Mass or painMass or pain

in the axillain the axilla

Palpable massPalpable mass ThickeningThickening PainPain

Nipple dischargeNipple discharge Nipple retractionNipple retraction

Edema or erythemaEdema or erythema

of the skinof the skin

Colorectal CancerColorectal Cancer

PhilippinesPhilippines 33rdrd leading cancer site leading cancer site

33rdrd in males in males 44thth in females in females

4rth leading cause of death4rth leading cause of death

RECTAL CANCERRECTAL CANCERSigmoidoscopySigmoidoscopy

All rights reserved.

Dr Ligoury, CNRI.

COLON CANCERCOLON CANCERFlexible sigmoidoscopyFlexible sigmoidoscopy

Dr Larpent, Clermont-Ferrand; CNRI.

All rights reserved.

Precancerous LesionsPrecancerous Lesions

G-E JunctionG-E Junction KidneyKidney

GERD / Acid refluxGERD / Acid reflux Intratubular Intratubular epithelial epithelial dysplasiadysplasia

H. Pylori infection H. Pylori infection

Genital WartsGenital Warts

Human Papilloma VirusHuman Papilloma Virus Main risk factor for cervical cancerMain risk factor for cervical cancer

Treatment:Treatment: VaccineVaccine Early detectionEarly detection

SkinSkin

Actinic keratosisActinic keratosis Atypical or dysplastic neviAtypical or dysplastic nevi Premalignant LentigoPremalignant Lentigo

Causes:Causes: UV radiationUV radiation GeneticsGenetics Exposure to carcinogens like Arsenic, Tar, Exposure to carcinogens like Arsenic, Tar,

X-rayX-ray

THANK YOU!THANK YOU!