25 HIGH YIELD POINTS OF GENERAL ONCOLOGY

[1] Anaplasia is considerd hallmark of malignant transformation.

[2] Most reliable feature to distinguish malignant vs benign is = MEASTASIS ( Next best = invasiveness).

 

[3] IMPORTANT PROTO-ONCOGENES TO REMEMBER

[*] RET = MEN 2A, MEN 2B & Familial medulary carcinoma thyroid.

[Note that complete loss of RET gene function leads to = HIRSCHSPRNG DISEASE]

[*] RAS :-

[a] K-RAS =Kolon(colon)

[b] H-RAS = Bladder & kidney tumors

[c] N-RAS = MELANOMA

[*] MYC :-

[a] C-MYC = Burkitt lymphoma

[b] N-MYC= NEUROBLASTOMA

[c] L-MYC= Lung = small cell carcinoma of lung

 

[4] Most common abnormality of dominant oncogene in human tumors is = Point mutation of RAS family.

Note:- P53 mutation is most common gene defect found in human tumors but it is a tumor suppressor gene.

So most common gene defect = P53, Most common oncogene involved = RAS , Most common tumor supp gene = P53.

 

[5] Phosphorylation of RB gene{Retinoblastoma, 13q14} is molecular on-off switch for cell cycle.

[6] Guardian of genome/Molecular policeman = P53 gene (ch 17p13.1)

P53 Gene [AIIMS 2004] [PGI 2002]

Major activities of this gene is cell cycle arrest ( act by activating p21 leading to G1/S arrest and less commonly by activating GADD45 leading to G2M arrest) and initiation of apoptosis.

MAIN ACTIVITY IS G1/S ARREST [AIIMS 2005]

Most common target for genetic alterations in human tumors (see above also)

Li-fraumani syndrome = inherited mutation in one p53 allele.

“Big brother of p53″ = p73

 

[7] Defects in DNA repair leads to ” genomic instability syndromes” and these are at increased risk of developing cancer.

eg = Defect in mismatch repair(MMR) gene= HNPCC (hereditary non polyposis cancer syndrome)

Defect in Nucleotide excision repair gene = Xeroderma pigmentosum[AIIMS 2005]

 

[8] Down regulation of E-Cadherin in tumor cells makes them non cohesive and this phenomena is important for tumor to metastasize.

[9] Most potent chemical carcinogen = Polycyclic aromatic hydrocarbon.

[10] Mutagenic potential is most commonly studied by = Ames test[ AI 2005] .Uses the ability of chemicals to induce mutation in bacterium Salmonella typhimurium. If chemical is carcinogenic then it converts the bacterium Hist- to Hist+ and mutated bacterium has the ability to grow in histidine deficient medium. It identifies > 90% of known carcinogens.

[11] UV Rays = Risk of devloping cancer = UV B > UV A > UV C [UV rays = formation of pyrimidine dimers]

[12] Most common radiation induced cancer = leukemia [ Note that CLL never develops after radiation].

 

[13] HPV Carcinogenesis

Viral protein E6 acts by degrading p53

Viral protein E7 acts by degrading RB

 

[14] EBV carcinogenesis

EBV = Enter B-cell via CD21——– LMP1 of virus activate —–CD40 receptor of B-Cells = Immortalisation of B-Cells.

 

[15] Germinal, hematopoetic stem cells and tumor cells express telomerase which protect length of telomers [AI 2006]

 

[16] Important for :-

[a] G1/S TRANSITION = Cyclin D/CDK 4

[B] G2/M TRANSITION = Cyclin B/CDK 1 [AIIMS 2003]

[C] Main propagotor of cell cycle that propels cell beyond prophase = CYCLIN B

[17] MAIN INHIBITORS OF CELL CYCLE = p21 , p27, p53, INK4/ARF family (They inhibit CDK) [AIIMS 2003]

[18] TELOMERE shortens with each cell division and causes growth arrest.

Telomerase is a enzyme that adds TTAGGG (= TELOMERE) at 3′ end of chromosome and is expressed by stem cells, germ cells and tumor cells.

[19] HNPCC is most common cancer predisposition syndrome.

[20] Relative biological effects(RBE) of radiations = NEUTRON > ALPHA PARTICLE > X-RAYS > GAMMA RAYS> ELECTRONS

[21] Cells are most sensitive to radiation in G2/M Phase ( M > G1) > Early S > Late S

[22] Highly Radioresistant tumors :-

[a] MELANOMA

[B] OSTEOSARCOMA

[C] PANCREATIC CA

[D] HEPATOMA

[23] Most radiosensitive tumor = Semonoma/Dysgerminoma.

[24] TUMOR LYSIS SYNDROME is charecterised by Hyperuricemia, Hyperkalemia , Hyperphosphatemiaa, Hypocalcemia, Lactic acidosis. [AI 2001 , AIIMS 2003]

[25] Radiation must produce ” double strand breaks” in DNA to kill a cell.

Advertisements

Cystic neoplasms of Pancreas (For AIPGME 2014)

Cystic neoplasms of pancreas include:

1. Serous cystic neoplasms (30%)
2.Mucinous cystic neoplasm (50%)
3. Intraductal papillary mucinous neoplasm

Serous cystic neoplasms (SCN)

Mean Age:62years

Site:Head of pancreas

Macroscopy:Small spongy clusters of clear cysts <2cms

CT scan: 1. Central sunburst/stellar scar appearance 2. Each cluster resembles BUNCH OF GRAPES 3. HONEYCOOMB appearance

Mucinous cystic neoplasm (MCN)

Mean Age: 53 years

Site:Body and uncinate process

Macroscopy: Large cysts >2cms (~ 6 in number)

CT scan:  Papillary invaginations into cyst (ovarian stroma +)

Intraductal papillary mucinous neoplasm (IPMN)

Mean Age:63yrs

Site:Head of pancreas ,tail of pancreas

Macroscopy: Pancreatic duct dilatation

CT scan:Fish mouth sign

SCN and MCN common in females and IPMN common in males.

Stereotactic Radiotherapy with Nov AIIMS 2012 Question.

Stereotactic radiotherapy-A specialized type of external beam radiotherapy which uses focused radiation beams targeting a well defined tumor,precise treatment set up to deliver the radiation dose with extreme accuracy (ie stereotactically).

There are two types of stereotactic radiation-

1)Stereotactic radiosurgery (SRS)-

One or several stereotactic radiation treatments of Brain and Spine.

-Glioma and other primary brain tumors

-Brain metastases

-Meningiomas

-Acoustic neuromas

-Brain AV malformations.

2) Stereotactic body radiation therapy (SBRT)-

One or several stereotactic radiation treatments with the body,excluding the Brain and Spine.

-Small lung cancer

-lung and liver metastases

Other Names for Stereotactic Radiation-

Cyber Knife,Gamma Knife,X-Knife,Tomo Therapy

Nov AIIMS 2012 Question-

Q.Stereotactic radiosurgery used in treatment of-

a.Brain

b.Lung

c.cervix

d.AV malformation

Ans-a. Brain>d.AV malformation

Q.Stereotactic body radiothearpy used in treatment of-

a.Brain

b.Lung

c.Cervix

d.AV malformation

Ans-b lung

Newer concept in radiotherapy and Oncology (Must for AIIMS)

3D  CRT (Three dimensional conformal radition therapy)-

Combines multiple radiation treatment fields to deliver precise doses of radiation to BRAIN.

Tailoring each of the radiation beams to patient’s tumor allows coverage of diseased cells while keepng radiation away from near by organ,such as eyes.

IMRT (Intensity modulated radiation therapy)-

IMRT differs from 3D-CRT by modifying the intensity of radiation within each of radiation beams.

Improved outcomes have been show for PROSTATE cancer patient receiving IMRT.

Radiolabelled antibodies-

These are newer most concept as a means to delivering high level of radiation locally to tumor bed,there by avoiding systemic toxicity.

Ibritumomab tiuxetan and tositumomab are first radiolabeled antibodies to be FDA approved for the treatment of cancer-specifically,relapsed low-grade non Hodgkin lymphoma.

RHABDOMYOSARCOMA [AIIMS MAY 2013]

Q] Marker used for identification of Rhabdomyosarcoma…[AIIMS MAY 2013]
[A] DESMIN
[B] VIMENTIN
[C] CYTOKERATIN
[D] S-100

OR which of the following is superior to other markers for identification of Rhabdomyosarcoma?

Ans = [A] DESMIN

Desmin is a intermediate filament and is a sensitive marker for tumors of both smooth and skeltal muscle origin. More than 90 % of Rhabdomyosarcomas are positive , including those that are very poorly differentiatedDesmin has been proven to be superior to other muscle markers for identification of Rhabdomyosarcoma. In smooth muscle tumors desmin reactivity is variable. Note that MYOGLOBIN is found exclusively in skeltal muscle lesions and so it is specific for Rhabdomyosarcoma but its sensitivity is far less than that of desmin.[Ref : Strernbergs diagonostic surgical pathology 5ed/ vol 1/ page 134]

VIMENTIN : It is known as intermediate filament of mesenchymal tissues however vimentin positivity is not that informative from a diagonostic point of view because many tumors including carcinomas and melanomas contain vimentin.

CYTOKERATIN (CK) : Cytokeratins are specific for tumors of epithelial origin. The two sarcomas that characteristically displays epithelial markers are = Synovial sarcoma & Epitheloid sarcoma .