Teratoma

Teratoma

• Tumor from totipotential germ cells
• Can differentiate along three germ layers
• Common in ovary and testis

• Mature teratoma(Benign): All tissues are mature
• Immature teratoma(Malignant): Elements of immautre tissue

• Malignant teratoma: Malignancy arising within mature teratomta

Hamartoma

benign-appearing masses composed of cells indingeous to the site

Cowden syndrome: PTEN genetic disorder characterized by multiple hamartomas

Anaplasia

loss of structural and functional differentiation of normal cells. Indicative of malignancy

Anaplastic Cells: Pleomorphism, increased mytosis, and atypical mitoses, large nuclei, bizare nuclear shapes

Differentiation

Well differentiated: closely resembles normal cell

Poorly differentiated: Does not resemble normal cell. Associated with anaplastic cells

Small round blue cell tumors

common neoplasms of infancy and childhood

Neuroblastoma

Wilms tumor

Retinoblastoma

Acute leukemias

rhabdomyoscarcomas

Neurofibromatosis 1

NF1 Gene

Lish nodules, cafe-au-lait spots

Autosomal dominant

Inherited Cancer Syndromes

Rb

p53

APC

NF1, NF2

BRCA1, BRCA2

MEN1, RET

MSH2, MLH1

PTEN

Inherited Cancer Syndromes

Rb: retinoblastoma

p53: Lif-raumeni syndrome

APC: FAP

NF1, NF2: Neurofibromatosis

BRCA1, BRCA2: Breast Cancer

MEN1, RET: Multiple endocrine neoplasia

MSH2, MLH1: Nonpolyposis colon cancer

PTEN: Cowden syndrome(epithelial cancers)

Defective DNA repair Cancers
Generally Autosomal Recessive

Xeroderma pigmentosa: nucleotide excission repair

Ataxia Telangiectasia: ATM- dsDNA breaks

HNPCC: DNA mismatch repair

CHD1 Gene

Encodes E-Cadherin

Mutation leads to lobular cancer of breast

EGF receptor family

Squamous cell Carcinoma. 80% of total

RAS

Mutation of RAS is most commone oncogene abnormality

Point mutatoin in 90% of pancreatic adenocarcinoma

Mutant RAS cannot inactivate by hydrolysis of GTP

Chronic Myeloid Leukemia(CML)

BCR-ABL hybrid has potent tyrosine kinsase activity → Growth promotion

Philadelphia chromosome: 9;22, BCR-ABL

Normal ABL protein causes apoptosis in DNA damage → Apoptosis is impaired in hybrid

Treated with Gleevac(Imatinib)

MYC

MYC protein induced rapidly when quiescent celsl receive cell division signal(Nuclear TF)

C-MYC: Burkitt lymphoma 8;14

N-MYC: Neuroblastoma(Double minutes) & SCC. Double minutes harbor oncogenes(gene amplification)

L-MYC: Small cell carcinoma

p53

Most human cancers have muation in p53

Li-fraumeni inherit one bad copy

E6 protien of HPV binds and degrades p53

Rb

Retinoblastoma

Key in cell cycle regulation(active form prevents progression)

Rb is inactive in hyperphosphorylated state in G1/S checkpoint

Inactive releases E2F → progression

APC/B-catenin

Tumor suprresor

Inherit mutation: FAP 1000's of polyps in late teens

B-catenin-E-cadherin germline mutation increases risk of gastric cancer

Tumor Supressor Genes

PTEN

NF1/NF2

VHL

WT1

Tumor Supressor Genes

PTEN: Cowdens

NF1/NF2: neurofibromatosis type 1/2

VHL: Renal cell carcinoma

WT1: Wilms tumor

Warburg Effect

Cancer cells use aerobic glycolysis

Allows visulation via PET

Gene Amplification

Double Minutes and homologous staining regions

N-myc and ERB2

Steps in chemical Carcinogenesis

Initiation & promoters

Steps in chemical carcinogenesis

Initiation causes permanent DNA damage and is not reversible

Promoters induce tumors in initiated cells but are reversible as theey do not affect the DNA

HTLV-1

Causes T-cell Leukemia and lymphoma

Tropism for CD4 lymphocytes

In japan and caribbean

Tax Gene stimulates proliferation

EBV Virus & Cancer

Burkitt Lymphoma t(8;14) Activates MYC gene

B cell lymphomas in immunocompromised

EBV genome found in 100% of nasopharyngeal carcinoma

LMP-1 induce angiogenic factors: VEGF, MMP9

HPV

What types in cancer?

HPV

Strains 16 and 18 in cervical and anogenital SCC

E6 and E7 viral proteins

Hepatitis B/C

&

Cancer

Hepatitis B/C

Chronic inflammation, hepatocellular injury, stimulation of hepatocyte proliferation and production of ROS that damage DNA

Acitvation of NF-KB pathway blocks apoptosis in hepatocytes

Grading and staging of tumors

Grade:  Degree of differentiation & number of mitosis

Stage: based on size of primary lesion, spread to lymph nodes and presense of blood born metastasis

T for Primary Tumor

N for regional lymph node involvement

M for metasis