Types of Lung Cancer
Ben Wiltsie
Biology of the Cancer Cell
8-5-04
Lung Cancer Statistics
Leading cause of death due to cancer in both men
and women-
It accounts for 14% of cancer cases and 28% of all
cancer deaths
Cigarette smoke is estimated to cause 87% of lung
cancer deaths
Only 10% of all lung cancer patients are ultimately
cured
173,770 new cases in 2004
160,440 deaths in 2004
Causes of Lung Cancer
• Lung cancer most common cancer and
most preventable
• Smoking leading cause
• Exposure to asbestos
• Exposure to radon
2 Major Types
• Small Cell
• Non-Small Cell
Small Cell Lung Cancer
• SCLC 20 – 25% of lung cancer cases
• Often called „oat cell‟ carcinoma
• Begins in bronchial submucosa, layer beneath
epithelium.
• Fast progression and early metastases
• Very often has already metastasized by the time of
diagnosis.
• 35 weeks average survival with treatment
• Patients often cough up metastatic small cells in mucous
• Source: Lung Cancer and Metastasis http://www.medicinenet.com/lung_cancer/page1.htm
SCLC deadlier than NSCLC
• Most aggressive type of lung cancer
• Symptoms are brief before cancer is
diagnosed- poor prognosis
• Often discovered through symptoms of
metastatic disease
• Develops in
• Patients are rarely surgical canidates
• Considered a systematic disease
• Oat shaped undifferentiated cell
• Invasion into neighboring tissue
• Early spread to lymphnodes
Causes of SCLC
• Smoking is the main cause
• Radiation exposure is also shown to
increase incidence of SCLC
• Exposure to industrial agents such as
chloromethyl ether
Genetic Factors for SCLC
• Myc oncogene often involved
– Reduced differentiation and increased proliferation
• Retinoblastoma gene mutated in almost all SCLC cases
– Less regulation of G1/S checkpoint
• P53 tumor suppressor mutations also very common
– Less regulation of G2/M checkpoint
• Deletion on Short Arm of Chromosome 3- 90% of SCLC
cases
– 3 known oncogenes
• Beta-retinoic acid receptor gene
• Zinc-finger containing genes
• Protein tyrosine phosphate (PTP)-gmma gene
• Tumor suppressing enzyme that regulates growth
2 Types of SCLC
• Classic- 70% • Variant
– Long doubling time • Grows more rapidly
– Poor ability to be cloned in • Shorter Doubling Time
vitro • Radio resistant
– Radiosensitive • Resemble large-cell
undifferentiated carcinoma
– Typical morphological
• Amplification of c-myc
features resembling gene
intermediate cell type
• 33 Week survival
– 53 week survival
– Source: Biology of small-cell lung cancer
http://web4.inf otrac.galegroup.com/itw/inf omark/92/462/
5338475ow.htm
Small Cell Diagnosis
• Usually seen as a mass in the center of the chest on x-
ray.
• SCLC patients survive 11 months average
• Primary tumor spreads to lymph nodes of the chest and
then to the blood.
• Commonly metastasize to the liver, bone, spinal cord,
kidneys pancreas and adrenal glands.
• Surgery is usually not an option because it has usually
already spread.
• Source: Lung Cancer and Metastasis http://www.medicinenet.com/lung_cancer/page1.htm
Genetic factors for NSCLC
• RB and p16 mutations involved in 50-80% of
NSCLC cases
– Non-functioning Rb cannot inactivate E2F to hold
transcription for DNA repair or cell growth
• K-Ras mutations in 90% of NSCLC cases
– Signaling pathway for proliferation and differentiation
• P53 mutations in about 60% of NSCLC cases
– Allows cells to continue and gain mutations with out
G1 arrest. Avoids apoptosis.
• Source; Cumulative Mutations of Pathways handout
• Tumor Progression and Metastasis: http://carcin.oupjournals.org/cgi/content/full/21/3/497
Types of Non-Small Cell
Carcinoma
• Large cell carcinomas- 10% of NSCLCs
• Fewer Structural features compared to other types
• Difficult to distinguish from secondary tumors from other organs
• Squamous cell carcinomas- 30-40% of NSCLCs
• Central location in lungs, usually bronchus
• Cause symptoms earlier in growth
• Coughing and phlegm are symptoms
• Shortness of breath
• Bronchoalveolar carcinoma
• Found throughout respiratory tract
• Good prognosis when still a single mass- 75-90% 5 year survival
• Poor survival after it spreads
• Adenocarcinoma- most common NSCLC in the U.S.
• Majority of these are found in the periphery of the lung and produce no
symptoms at the time of diagnosis.
• Tend to metastasize to the bone, central nervous system, adrenal glands
and liver.
Squamous cell
• 30% of all lung cancers- most common
worldwide
• Large association with smoking
• Slow progression and late to metastasize
• Removed Surgically before it spreads
• Over 50% 5 year survival when detected
before spreading
• Source: Lung Cancer: http://www.alahv.org/bookfiles4/lung_cancer.html
• Epithelial origin- cells
lined up
• Nuclei are large and
irregular
• Nuclei not centrally
located in the cell
• Squamous
metaplasia in
adjacent epithelium
Adenocarcinoma
• 35% of all lung cancers- increasing in U.S.
• Most Common type in women and non-smokers
• Developed in out edges of lung
• Cube or column shaped cells
• Small association to smoking
• Average progression rate and ability to spread
• Surgical removal unlikely
• Less than 10% 5 year survival
• Source: Lung Cancer: http://www.alahv.org/bookf iles4/lung_cancer.html
• Adenocarcinoma
– Stained for CD15.
– Dark staining in neoplastic cells
Large Cell Lung Cancer
• 15% of all lung cancers
• Cancers that do not fit into the other categories
• Developed between outer edges and central
lung
• Large association to smoking
• Very fast progression with an early ability to
spread
• Surgical removal unlikely
• Less than 10% 5 year survival
• Source: Lung Cancer: http://www.alahv.org/bookf iles4/lung_cancer.html
Other types of lung cancer
• Secondary lung tumors
– Can result from primary metastatic tumors of the
bladder, breast, as well as melanoma, osteosarcoma,
renal adenocarcinoma,testicular cancer and thyroid
carcinoma
• Mesothelioma
– Cancerous tumor of lining of lung and chest- pleura
– Almost always caused by exposure to asbestos
– Smoking dramatically increases risk
– 20-25 years between asbestos exposure and
symptoms
• Source: Lung Cancer: http://www.alahv.org/bookf iles4/lung_cancer.html
Treatment
• Radiation therapy for patients with regional
nodal involvement
• Chemotherapy used to treat patients with
full metastatic cancer
– Best method to treat small cell
• Surgical removal before metastasis
– Small cell cancers have usually spread by the
time of diagnosis
Differences between NSCLC and
SCLC
• Small Cell • Non-small cell
– Metastasizes early – Metastasizes late
– Shorter Latency – Long latency period
– Usually discovered after – Usually discovered and
spreading to regional treated before it spreads
nodes – Slow growing and
– Resemble oats- oat cells progressing
– Poor prognosis and very – Good prognosis if
low 5 year survival discovered early
– Treated with radiation and – Higher 5 year survival than
chemotherapy SCLC
– Patients die at a younger – Treated with surgery before
age metastasis. After Radiation
and Chemotherapy
Sources:
• “CD15 in neoplasms” NIQC, Aug 20, 2003. http://www.nordiqc.org/Epiropes/CD15-fig2.htm.
• “Lung Cancer” Cedars-Sinai http://www.cedars-sinai.edu/5270.html.
• “Lung Cancer, Small Cell” eMedicine, Jan 27, 2004. http://www.emedicine.com/RADIO/topic405.htm.
• “Squamous cell crcinoma of lung” ttp://www.brown.edu/Courses/Digital_path/lungs/suamous_cell_carcinoma.htm.
• “Thyroid transcription factor-1” NIQC, Aug 20, 2003. http://www.nordiqc.org/Epiropes/TTF/TTF -1.htm.