Pre-Cancerous Lesions:
Red Flags for future
Cancers
Gerardo H. Cornelio.MD, FPCP, FPSMO, FPSO
Magnitude of Cancer Problem
in the Philippines
INCIDENCE




3rd in incidence after communicable &
cardiovascular diseases
1 out of 1,000 Filipinos has cancer
114:103 Females to Males, Filipino
Incidence rates increase w/ Age:
 0-14 yr.: 3.6% of cancers
 >35 yr.: 91% of cancers
 >=50 yr.: 76% of cancers
THE TEN LEADING CANCER SITES
IN THE PHILIPPINES
16.00%
14.00%
12.00%
10.00%
8.00%
6.00%
4.00%
2.00%
0.00%
Lung
Breast
Liver
Cervix
Leukemias
Colon
Thyroid
Stomach
Nasopharynx
Lymphomas
Philippine Cancer Facts and Estimates, 1998
ESTIMATED LEADING CAUSES
OF CANCER DEATHS
#
O
F
C
A
S
E
S
LUNG
10,000
9,000
8,000
7,000
6,000
5,000
4,000
3,000
2,000
1,000
0
LIVER
BREAST
CERVIX
COLON
STOMACH
PANCREAS
PROSTATE
RECTUM
CANCER SITES
Philippine Cancer Facts and Estimates, 1998
TEN LEADING CANCER SITES IN
MALES
NASOPAHRYNX(7)
LUNG(1)
PROSTATE (3)
COLON(5)
RECTUM(9)
ORAL(10)
LYMPHOMA (8)
STOMACH(6)
LIVER(2)
LEUKEMIA(4)
Philippine Cancer Facts and Estimates, 1998
TEN LEADING CANCER SITES IN
WOMEN
BREAST(1)
THYROID(4)
LUNG(3)
LIVER(8)
OVARY(5)
CERVIX(2)
STOMACH(9)
UTERUS(10)
COLON(7)
LEUKEMIAS(6)
Philippine Cancer Facts and Estimates, 1998
What are the Top Ten
Cancers in the Philippines?
Male
Female
Child
Lung
Breast
Leukemia (ALL)
Liver
Cervix
Lymphoma (NHL)
Stomach
Lung
Colon
Ovary
Brain/ Spinal (Medullablastoma;
Astrocytoma)
Retinoblastoma
Rectum
Stomach
Bone (Osteosarcoma)
Nasopharynx
Leukemia
Oral cavity
Pancreas
NHL
Liver
Thyroid
Oral cavity
Colon
Rectum
STS (Rhabdo-myosarcoma)
Kidney (Wilm’s)
Gonadal GCT
Epithelioma
Genetics
CANCER
Environment
Proliferation
Anaplasia
Clinical Manifestations
Metastasis
Biopsy
DIAGNOSIS
Preventive
Curative
Supportive
Staging
MANAGEMENT
THE NINE WARNING SIGNS
C
•Change in bowel or bladder habits.
A
•A sore that does not heal.
U
•Unusual bleeding or discharge.
T
•Thickening of a lump in breast or elsewhere.
I
•Indigestion or difficulty in swallowing.
O
•Obvious change in a wart or mole.
N
•Nagging cough or hoarseness.
U
•Unexplained anemia.
S
•Sudden, unexplained weight loss.
What is Cancer?
CANCER CELLS AND NORMAL
CELLS
CANCER CELLS
NORMAL CELLS
Frequent
mitoses
Normal
cell
Nucleus
Blood vessel
Few
mitoses
Abnormal
heterogeneous cells
Loss of contact inhibition
Oncogene expression is rare
Increase in growth factor secretion
Intermittent or co-ordinated
growth factor secretion
Increase in oncogene expression
Loss of tumor suppressor genes
Presence of tumor suppressor
genes
Cancer Genes



Proto-oncogenes – normally promote normal
cell growth; mutations convert them to
oncogenes.
Tumor suppressor genes – normally restrain cell
growth; loss of function results in unregulated
growth.
DNA repair genes – when faulty, result in an
accumulated rate of mutations.
ONCOGENES
ONCOGENE
SIS
ERB1
FMS
KIT
MET
HER2/ NEU/ ERBB2
RET
TRKA
ERBA
RAS (H,K,N)
BCR-ABL
RAF
SRC
FUNCTION
Platelet-derived growth factor
Epidermal growth factor
CSF-1 receptor
Stem cell growth factor receptor
Hepatic growth factor receptor
Heregulin receptor
Neurotrophic growth receptor
Nerve growth factor receptor
Thyroid hormone receptor (nuclear)
GTPase
Cytoplasmic tyrosine kinase
Cytoplasmic tyrosine kinase
Cytoplasmic tyrosine kinase
FOS
JUN
MYC (c,L,N)
Transcription factor
Transcription factor
Transcription factor
BCL6
BCL2
Transcription factor
Anti-apoptosis
ASSOCIATED HUMAN CANCER
Papillary renal cancer
Cancer of breast, ovary, bladder; glioblastoma
Medullary thyroid cancer
Cancer of lung, pancreas, bladder, colon, rectum
Chronic myelogenous leukemia
Burkitt’s lymphoma, neuroblastoma, lung
cancer
Large cell lymphoma
Prostate cancer, lymphoma
Multistage Carcinogenesis
CARCINOGENS


Occupation related causes
Lifestyle related causes







Tobacco
Diet
Sexual practices
Multifactorial causes
Viral carcinogens
Chemical carcinogens
Ionizing radiation
Occupational Risk Factors
Etiology
Site of Malignancy
Arsenic
Asbestos
Benzene
Benzedine
Chromium cpds
Radiation (mining)
Mustard gas
Polycyclic hydrocarbons
Vinyl Chloride
Lung, skin, liver
Mesothelium, lung
Leukemia
Bladder
Lung
Numerous locations
Lung
Lung, skin
Angiosarcoma of liver
Lifestyle Risk Factors
Tobacco-related:
 Lung cancer
 Pancreatic cancer
 Bladder cancer
 Renal cancer
 Cervical cancer
Diet-Related Risk Factors
Nitrates
Salt
Low vitamins A, C, E
Low consumption of
yellow-green vegetables
Gastric Cancer
Esophageal
Cancer
Diet-Related Risk Factors
High fat
Low fiber
Low calcium
High boiled or
fried foods
Colon Cancer
Pancreatic Cancer
Prostate Cancer
Breast Cancer
Uterine Cancer
Mycotoxins
Liver Cancer
Sexual Practices Risk Factors
Sexual promiscuity
Multiple partners
Unsafe Sex
Human Papillomavirus
Cervical Cancer
Multifactorial Factors
Tobacco + Alcohol
Tobacco + Asbestos
Tobacco + mining
Tobacco + uranium +
radium
Oral Cavity Cancer
Esophageal Cancer
Respiratory Tract
Cancer
Lung Cancer
Chemical Carcinogenesis
Normal Cells
Initiator(s)
(electrophilic, mutagenic)
Chemical
Carcinogen
Promoter(s)
Inactive Metabolites
Initiated Cells
Tumor Cells
Clones
Gross Tumors
Radiation Carcinogenesis


Radiation-induced mutation in the host cell
Transmits irreversible changes in gene
expression to cell progeny
Sources of Potentially
Carcinogenic Radiation





Sunlight
Artificial sources of UV light
X-rays
Radio-chemicals
Nuclear fission
Viral Carcinogenesis
 Viral
carcinogens are classified into RNA and
DNA viruses.
 Most
RNA oncogenic viruses belong to the
family of retroviruses that contain reverse
transcriptase
mediates transfer of viral
RNA into virus specific DNA.
Sequence of Disease Progression
Leukoplakia / Erythroplakia
Dysplasia
Carcinoma in situ
Invasive Carcinoma
Regional / Distant Metastasis
Lung Cancer Profile
Smoke: 25 or more
15 – 24
14 or lower
+ 50
+ 25
+ 10
1 or more cigars the past year
+5
3 or more vegetables a day
-5
Parent, brother or sister w lung cancer
+ 10
Lived with a smoker
+5
Live near a large city for 10 years
+5
Asbestos worker without protection 5-20 yrs/ >20
+25 /50
Radon, Cadmium, aluminum, silica, sulfur 5-20 />20
+10 / 25
Eats 3 or more servings of fruits per day
-5
Risk Chart
Score
Your risk is:
Less than 0
Very much below average
0-6
Much below average
7 - 10
Below average
11 - 12
Average
13 - 21
Above average
22 - 53
Much above average
54 or higher
Very much above average
Lung Cancer

Bronchial intraepithelial lesions

Squamous metaplasia or dysplasia in former
smokers

Loss of retinoic acid receptor-B expression
BREAST CANCER
Signs and symptoms at
presentation

Mass or pain
in the axilla

Palpable mass

Thickening

Pain

Nipple discharge

Nipple retraction

Edema or erythema
of the skin
Non Invasive Breast Cancer

Lobular Carcinoma in situ (LCIS)



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Premalignant
20% develop IBC over 15 years
30% bilateral
Annual mammography / Tamoxifen risk reduction (56%) –
NSABP P1
Ductal Carcinoma in situ (DCIS)



Malignant
Recurs in 35% in 10-15 yrs if biopsy alone
>25% develop IBC
BREAST CANCER
Mammography
BREAST CANCER
Signs and symptoms at
presentation

Mass or pain
in the axilla

Palpable mass

Thickening

Pain

Nipple discharge

Nipple retraction

Edema or erythema
of the skin
BREAST CANCER
Signs and symptoms at
presentation

Mass or pain
in the axilla

Palpable mass

Thickening

Pain

Nipple discharge

Nipple retraction

Edema or erythema
of the skin
Colorectal Cancer

Philippines

3rd leading cancer site
 3rd
in males
 4th in females

4rth leading cause of death
RECTAL CANCER
Sigmoidoscopy
All rights reserved.
Dr Ligoury, CNRI.
COLON CANCER
Flexible sigmoidoscopy
All rights reserved.
Dr Larpent, Clermont-Ferrand; CNRI.
Precancerous Lesions

G-E Junction
 GERD

/ Acid reflux
H. Pylori infection
Kidney
Intratubular epithelial
dysplasia
Genital Warts

Human Papilloma Virus

Main risk factor for cervical cancer

Treatment:
Vaccine
 Early detection

Skin

Actinic keratosis
Atypical or dysplastic nevi
Premalignant Lentigo

Causes:


UV radiation
 Genetics
 Exposure to carcinogens like Arsenic, Tar, X-ray

THANK YOU!