Neoplasia (M) Flashcards
What is neoplasia?
It is the abnormal mass of tissue
What is the characteristic of neoplasia?
The growth of w/c is virtually autonomous and exceeds that of normal tissues
True or False
Growth of tumors persists after cessation of the stimulus that initiated the change
True
What is the meaning of term neoplasia?
It means new growth and does not imply benign / malignant
True or False
There are benign neoplasms, and there are malignant neoplasms
True
What are the 2 broad categories of neoplasms?
1) Benign
2) Malignant
What are the characteristics of benign neoplasm?
1) It is common in younger age grp
2) It grows slowly, usually by expansion
3) It is not fixed to the tissues, movable, easily removed at operations w/ less chances of recurrence
4) It is usually encapsulated
5) Metastasis is rarely observed, w/ no blood or lymphatic invasion
* 6) Pt’s w/ this has no cachexia
7) The cells w/c look more like normal cells differentiated, less mitotic figures (<1/1,000 cells), not hyperchromatic, less tendency to hemorrhage and necrosis
What is cachexia?
It is a condition that causes the body muscles to waste away is observed
What are the characteristics of malignant neoplasia?
1) It is common in the older age grp
2) It grows rapidly either by infiltration / by expansion
* 3) The metastasis is produced thru lymphatic and blood invasion
4) It produces ultimate death either by cachexia, mechanical pressure, hemorrhage, and infection
5) It is undifferentiated, more mitotic figures (20/1,000 cells), and hyperchromatic
6) It has more tendency to hemorrhage and necrosis
What are the 2 components of neoplastic tissues?
1) Parenchyma
2) Stroma
What is parenchyma?
It is the transformed neoplastic cells
What is the characteristic of parenchyma?
It is the active element of neoplastic tissues
What is stroma?
It is the connective tissue framework w/ lymphatic and vascular channels
What are the nomenclature for general categories of neoplasms (for malignant tumors)?
1) Carcinoma
2) Sarcoma
What is carcinoma?
These are malignant tumors of the epithelial tissue organ
What is the characteristic of carcinoma?
It has the less tendency to produce supporting tissue / stroma
What is sarcoma?
These are malignant tumors of connective tissue origin
What is the characteristic of sarcoma?
These are characterized by abundant intercellular tissue framework (fat muscle)
*What are the nomenclature for general categories of neoplasms (for malignant neoplasms)?
1) Lymphoma
2) Melanoma
What is lymphoma?
These are malignant neoplasms derived from lymphocytes
What is melanoma?
These are malignant neoplasms w/c are derived from melanocytes
What are the exs of nomenclature for benign neoplasms?
1) Adenoma
2) Fibroadenoma
3) Leiomyoma
What is adenoma?
It is the benign neoplasm of glandular epithelium
What is fibroadenoma?
It is the benign neoplasm of the breast
What is leiomyoma?
It is the benign neoplasm of smooth muscle
What are some exceptions w/ regards to the nomenclature for benign neoplasms?
1) Hepatoma
2) Melanoma
3) Mesothelioma
4) Seminoma
What is hepatoma?
It is the malignant neoplasm of liver
What is melanoma?
It is the malignant neoplasm of melanocytes
What is mesothelioma?
It is the malignant neoplasm of mesothelial cells
What is seminoma?
It is the malignant germ cell neoplasm of testis
What are the exs of nomenclature for malignant neoplasms?
1) Adenocarcinoma
2) Rhabdomyosarcoma
3) Leiomyosarcoma
What is adenocarcinoma?
It is the malignant neoplasm of glandular tissue
What is rhabdomyosarcoma?
It is the malignant neoplasm of skeletal muscle
What is leiomyosarcoma?
It is the malignant neoplasm of smooth muscle
*What is the principle of differentiation of terminologies related to the microscopic appearance of neoplasms?
How histologically similar to the normal tissue the neoplasm (i.e., how analogous the neoplastic cells look to the tissue type from w/c they arose)- terms used are well differentiated, or poorly differentiated
True or False
Differentiation is not a subjective determination made by the patho
False, because differentiation is a subjective determination made by the patho
What is the characteristic of anaplasia?
It lacks differentiation
What is dysplasia?
It is the disordered growth of epithelium
What are the characteristics of dysplasia?
1) There is a loss of cellular uniformity and architectural orientation
2) The cells may have an increased # of mitotic figures
3) It does not necessarily form a mass or tumor
4) In many cases, it is a precursor of malignancy, but it does not always progress to malignancy
5) It can be reversible, if the inciting agent is removed
What is the characteristic of carcinoma present in situ?
Presence of full-thickness dysplasia of the epithelium
*In terms of terminology, is the term carcinoma in situ related to neoplasms?
Yes, it is a miscellaneous terminology related to neoplasms
What is hamartoma?
It is a disorganized collection of tissue, w/ the tissue composing the mass being tissue that is normally found in the organ in w/c the mass occurred
What is the characteristic of hamartoma?
It is not a neoplasm
What is choristoma?
It is a mass composed of ectopic tissue
What are the characteristics of choristoma?
1) It is otherwise a fairly normal tissue
2) It is located at a site where it normally is not found
3) It is not a neoplasm
What is polyp?
It is a mass projecting from a mucosal surface
In terms of terminology, what is the characteristic of the term polyp?
It is not a descriptive term
True or False
The mass causing polyp is a neoplasm
False, because the mass causing polyp may or may not be a neoplasm
*What are the terminologies related to the microscopic appearance of (neoplasms?)?
1) Anaplasia
2) Dysplasia
3) Carcinoma in situ
4) Hamartoma
5) Choristoma
6) Polyp
What are the features used to distinguish benign neoplasms from malignant neoplasms?
1) Histologic features of malignancy
2) Rate of growth
3) Invasion and metastases
What is the principle of histologic features of malignancy (as a feature used to distinguish benign neoplasms from malignant neoplasms)?
Histologic features are reliable indicators of malignancy in many organs, although in some sites
What are the histologic features of malignancy that can be observed (as a way to distinguish benign neoplasms from malignant neoplasms)?
1) Pleomorphism
2) Abnormal mitotic figures
3) Hyperchromasia
4) Hypercellularity
What is pleomorphism?
It is the variation in nuclear and cytoplasmic shape bet cells
What is associated along abnormal mitotic figures (that can be used to distinguish benign neoplasms from malignant neoplasms)?
Increased #s of mitotic figures
What is hyperchromasia?
It is the condition where there is an increased basophilia (/ basophils) of the nucleus
What is associated along hypercellularity (that can be used to distinguish benign neoplasms from malignant neoplasms)?
It is associated w/ a loss of normal polarity
What is the principle of rate of growth (as a feature used to distinguish benign neoplasms from malignant neoplasms)?
Benign neoplasms tend to grow slower whereas malignant neoplasms tend to grow more quickly often at a rate corresponding to their degree of anaplasia
*What is under rate of growth?
Growth fraction
What is growth fraction?
It is the proportion of neoplastic cells in the proliferative phase
What is the percentage of growth fraction at the point when most malignant tumors are clinically detected?
It is usually < 20%
What is the characteristic of most neoplasms (in connection to rate of growth)?
Most neoplasms have their most rapid rate of growth prior to detection
What is the principle of invasion and metastases (as a feature used to distinguish benign neoplasms from malignant neoplasms)?
Histologic features and rate of growth alone cannot always distinguish bet benign and malignant neoplasms
What are the 2 features that reliably distinguish benign from malignant neoplasms (in connection to invasion and metastases)?
1) Invasion
2) Metastasis
What is invasion?
It is the infiltration of tumor cells into surrounding organs
What is metastasis?
It is the spread of tumor cells to distant organs through the blood
What is the characteristic of sarcomas (in relation to metastasis)?
The spread of tumor cells to distant organs through the blood
What is the characteristic of carcinomas (in relation to metastasis)?
The spread of tumor cells to distant organs through the lymphatics
What are the viruses associated w/ neoplasms?
1) Human T-cell leukemia virus type 1 (HTLV-1)
2) Human papillomavirus (HPV)
3) Epstein-Barr virus (EBV)
4) Hepatitis B virus (HBV)
5) Helicobacter pylori
6) Human herpesvirus 8 (HHV-8)
What is the neoplasm associated w/ HTLV-1?
Adult T-cell leukemia / lymphoma
What is the mechanism of HTLV-1?
TAX gene of HTLV-1 can activate transcription of host cell genes, including c-fos and IL-2, w/c are both impt in the proliferation and differentiation of T cells
What is the neoplasm associated w/ HPV?
Squamous cell carcinoma of the cervix
What is the mechanism of HPV?
Production of viral E6 and E7 proteins, w/c interfere w/ the fxn of p53 and RB, respectively
What are the neoplasms associated w/ EBV?
1) Burkitt lymphoma
2) Post-transplantation lymphoproliferative disorder
3) B-cell lymphomas in AIDS pts
4) Nasopharyngeal carcinoma
5) Some cases of Hodgkin lymphoma
What is the mechanism of EBV?
EBV enters B cells through binding w/ CD21. EBV viral genes activate the transcription of latent membrane protein-1 (LMP-1), w/c activates nuclear factor-κβ (NF-κβ and JAK / STAT) (Janus kinase / signal transducers and activation of transcription) signaling pathway. Activation of the JAK / STAT pathway promotes B cell survival
What is the associated neoplasm w/ HBV?
Hepatocellular carcinoma
What is the mechanism of HBV?
Through chronic inflammation; also because HBV protein binds p53, interfering w/ its fxn
*What are associated w/ helicobacter pylori?
MALTomas of the stomach (neoplasm of mucosa-associated lymphoid tissue [MALT])
*What are associated w/ HHV-8?
1) Primary effusion lymphoma
2) Kaposi sarcoma
*What are the diff types of effects of tumors?
1) Effects of tumors based upon location
2) Types of paraneoplastic syndromes
a. Hormone production
*What is the principle of effects of tumors based upon location (as part of effects of tumors)?
Consider the location of the tumor to determine the effects
*Provide an ex of the principle of effects of tumors based upon location (as a part of effects of tumors)?
A 2.0 cm tumor in the brainstem may kill a pt; a 2.0 cm tumor in the leg may not even be noticed
What are the various effects of neoplasms that are extensive and not exhaustive (w/c may have based upon there location)?
1) A space-occupying lesion can obliterate bone marrow causing pancytopenia, impinge upon the brain leading to herniations, or it can block a cardiac valve orifice
2) Growth of a mass can impinge upon vasculature and can cause ischemia and infarction of tissue (w/ arterial compression) or congestion and infarction of tissue (w/ venous compression)
3) Invasion of a nerve can lead to neurologic deficits or pain
4) A mass can cause ulceration of overlying mucosa
5) A mass in the brain can serve as a focus for seizures or other neurologic deficits
6) A mass can obstruct the colon causing constipation; obstruct the bile duct causing jaundice; or obstruct the bronchus causing pneumonia or bronchiectasis
7) Bone destruction can lead to fracture (i.e., pathologic fracture)
What is cachexia?
It is the loss of body fat and muscle; weakness and anorexia associated w/ a neoplasm
*What is the mechanism of cachexia?
It is caused by cytokines produced by the tumor (possibly TNF) and by host response to the tumor
What are paraneoplastic syndromes?
These are side effects of a neoplasm not attributable to fxns normally associated w/ the cell type of origin or by the location of the tumor
In connection to hormone production, what is the mechanism of the production of parathyroid hormone (PTH)-like protein?
PTH like protein is produced by squamous cell carcinoma of the lung, breast carcinoma, and renal cell carcinomas; results to hypercalcemia
In connection to hormone production, what is the mechanism of the production of adrenocorticotropic hormone (ACTH)-like protein?
ACTH-like protein is produced by small cell lung carcinoma and pancreatic carcinoma; results in Cushing syndrome
*In connection to hormone production, what is the mechanism of the production of syndrome of inappropriate antidiuretic hormone (SIADH)?
SIADH is produced by the small cell carcinoma of the lung and cerebral neoplasms; results in retention of H2O
In connection to hormone production, what is the mechanism of the production of erythropoietin (EPO)?
EPO is produced by renal cell carcinoma, hepatocellular carcinoma, and cerebellar hemangioblastoma; results in polycythemia
*What are the characteristics of carcinogenesis?
1) Acquire self-sufficiency in growth signals and ignore growth inhibitory signals
2) Evade apoptosis, since apoptosis is the body’s mechanism to rid itself of cells w/ genetic damage so they cannot propagate that damage
3) Acquire defects in DNA repair
4) Acquire the ability to divide an unlimited # of times
5) Promote angiogenesis
6) Invade surrounding tissue, passing through the basement membrane and spreading to distant organs (i.e., metastasize)
*What is the process (or steps) of carcinogenesis?
1) The cell acquires mutations, which are nonlethal, so the cell can survive to divide and thus propagate the mutations. Mutations are acquired through damage caused by initiators. Promoters cause cell growth through promotion of the cell cycle and thus cause the propagation of mutations induced by initiators. Neither an initiator nor a promoter acting on its own can cause neoplasia; both must act on the cells. Genes most commonly affected during carcinogenesis
2) Proto-oncogenes: Proto-oncogenes are genes commonly used during normal growth and development; without control, they have the potential to produce neoplasms through their uncontrolled expression. Oncogenes are genes that have made the transition and are now capable of producing neoplasms. Most commonly, oncogenes cause unregulated cell growth through promotion of cellular division, which results in further mutations
3) Tumor suppressor genes: Genes that function to help control cell growth; their loss thus results in uncontrolled cell growth through loss of regulation of division.
4) Apoptosis genes
5) DNA repair genes
What are the impt points regarding genes involved w/ carcinogenesis?
1) No one mutation will result in a malignant neoplasm; malignant neoplasms result from the survival of cells that have accumulated multiple mutations.
2) Conversion of one of the two allelic genes from a protooncogene to an oncogene is sufficient to promote neoplasia. However, it requires loss of both tumor suppressor genes to promote neoplasia, as one of the two genes is sufficient to produce enough product to inhibit neoplasia.
What are the roles of oncogenes?
1) Synthesize growth factors
2) Synthesize growth factor receptors
3) Synthesize signal-transducing proteins
4) Synthesize nuclear transcription factors
5) Loss of regulation of cyclins and cyclin- dependent kinases
*What is the principle of synthesizing growth factors (as a role of oncogenes)?
Synthesize growth factors to w/c the neoplastic cell is also responsive
Provide an ex of synthesizing growth factors (as a role of oncogenes)?
Glioblastomas produce PLT derived growth factor (PDGF)
Provide exs of the role of oncogenes w/c is to synthesize growth factor receptors
1) RET receptor for glial cell line-derived neurotrophic factor- in medullary and papillary thyroid carcinoma (MEN syndrome)
2) ERB B1, an epidermal growth factor (EGF) receptor, is overexpressed in squamous cell carcinoma of the lung
3) ERB B2, an EGF receptor, is overexpressed in 25% of breast carcinomas
*Provide an ex of a sp gene that is associated w/ the role of oncogenes w/c is to synthesize signal-transducing proteins
RAS gene
What is the principle of incidence of mutations in RAS gene?
Mutations of the RAS gene are in 30% of all malignant neoplasms and in 90% of pancreatic adenocarcinomas
What is the principle of the role of normal RAS gene?
The RAS gene codes for protein that is associated w/ a growth factor receptor. When stimulated by a growth factor, RAS binds guanosine triphosphate (GTP) and activates the mitogen-activated protein (MAP) kinase pathway, which results in activation of transcription. The RAS protein is controlled by its GTPase activity; it cleaves the GTP bound to it to guanosine diphosphate (GDP), which inactivates the RAS protein
What is the principle of effects of mutations in the RAS gene?
The RAS protein loses its GTPase activity, so it remains activated, resulting in continual promotion of transcription
*Provide an ex of a sp gene that is associated w/ the role of oncogenes w/c is to synthesize nuclear transcription factors
MYC gene
What are the neoplasms that are associated w/ mutations of the MYC gene?
1) Burkitt lymphoma Also amplified in: 2) Breast 3) Lung 4) Colon cancers
What is the principle of the role of normal MYC gene?
MYC protein binds to DNA and activates transcription of several genes, including cyclindependent kinases (CDK). CDK proteins help drive the cell through the cell cycle
What is the principle of the effect of activation to oncogene?
Overexpression of MYC results in overpromotion of the cell cycle
What is implied by two-hit hypothesis?
It implies that w/ many hereditary neoplasms, a tumor suppressor gene is involved
Is the protein product from 1 gene is enough to prevent neoplasms from developing?
Yes
True or False
The protein product from 1 gene is enough to prevent neoplasms from developing, however, individuals born w/ a mutation of 1 gene are 1 step closer to the development of a neoplasm than those born w/ 2 normal genes
True
*In relation to mutations in tumor suppressor genes, what should be done?
Select tumor suppressor genes
*In connection to selecting tumor suppressor genes w/c should be done in relation to mutations in tumor suppressor genes, what are the most common tumor suppressor genes w/ mutations within neoplasms?
1) Retinoblastoma
2) p53
*What are the tumor suppressor genes that mutate?
1) Retinoblastoma (RB) gene
2) p53 gene
3) Other tumor suppressor genes
a. APC / β-catenin
b. INK4a / ARF
c. TGF-β (transforming growth factor beta)
d. NF-1
e. VHL
f. PTEN (phosphatase and tensin homologue)
4) Apoptosis genes
a. Bel-2
b. p53
What are the associated neoplasms in RB gene mutation?
1) Familial retinoblastoma
2) Osteosarcoma
3) Breast cancer
4) Small cell lung carcinoma
What is the role of normal RB gene?
Retinoblastoma binds E2F transcription factor, w/c is needed for the cell to move from the G1 phase of the cell cycle to the S phase. When retinoblastoma is phosphorylated, the E2F is released and the cell moves through the cell cycle
What are the effects of mutations of RB gene?
It can affect retinoblastoma / the proteins that phosphorylate retinoblastoma, resulting in hyperphosphorylation of RB
*What is the incidence of p53 gene?
Mutations of the p53 gene are found in more than 70% of tumors
What are the roles of p53 gene?
- 1) It is activated by DNA damage
2) It arrests the cell cycle by transcription of CDK21 (p21)
3) It promotes production of GADD45
4) If cellular damage is not repaired, it promotes the induction of the Bax gene
What are the fxns of CDK1 (p21)?
1) It inhibits cyclin / CDK complexes
2) It prevents phosphorylation of RB
What is the fxn of GADD45?
It helps repair the cell
What is the fxn of p53?
If cellular damage is not repaired, its production is induced w/c in turn promotes apoptosis
What are the other tumor suppressor genes?
1) APC / β-catenin
2) INK4a / ARF
3) TGF-β
4) NF-1
5) VHL
6) PTEN
What is the normal fxn of the protein product APC / β-catenin?
APC protein down-regulates β-catenin
What is the result of mutation of APC / β-catenin?
Elevated lvls of β-catenin result in interaction w/ TCF
The elevated lvls of β-catenin w/c result in interaction w/ TCF results in what?
It results in increased lvls of c-MYC and cyclin D1
What are the percentages of incidence of APC / β-catenin?
1) It is found in 70 - 80% of nonfamilial colon carcinomas
2) It is also found in 50% of hepatoblastomas
3) It is also found in 20% of hepatocellular carcinomas
What is the normal fxn of the protein product INK4a / IRF?
It blocks cyclin D-CDK4 activity in the cell cycle
What are the percentages of incidence and of INK4a / IRF and in what cases are this incidentally present?
1) 20% of familial melanomas
2) 50% of pancreatic adenocarcinomas
3) Present in squamous cell carcinomas of the esophagus
What are the percentages of incidence and of TGF-β and in what cases are this incidentally present?
1) It is inactivated in 70% > of colon cancers in pts w/ hereditary nonpolyposis colon cancer (HNPCC)
2) It is incidentally present in pts w/ sporadic colon cancer w/ microsatellite instability
What are the associated mutations of TGF-β?
SMAD4 w/c is originally termed as DPC4 (deleted in pancreatic cancer)
What is the fxn of SMAD4?
It encodes part of the TGF-β growth inhibitory pathway
Mutations of SMAD4 are seen in what percentage of cases?
It is seen in 50% of cases of pancreatic adenocarcinomas
What is the normal fxn of the protein product NF-1?
Neurofibromin is a GTPase-activating enzyme
What is the effect of mutation of NF-1?
RAS is trapped in an active form
What are the associated neoplasms of NF-1?
1) Neurofibromas
2) Malignant peripheral nerve sheath tumors
What is the normal fxn of the protein product VHL?
VHL protein is a ubiquitin ligase whose substrate includes HIF-1
What is the fxn of HIF-1?
It regulates vascular endothelial growth factor (VEGF)
What is the associated neoplasms of VHF?
Nonfamilial renal cell carcinomas
What is the normal fxn of the protein product PTEN?
It blocks the cell cycle
How does PTEN block the cell cycle?
It blocks the cell cycle by increased transcription of p27
What is the effect of mutation of PTEN?
Cells are allowed to easily progress into the cell cycle
In what conditions is PTEN incidentally present?
It is frequently found in:
1) Endometrial carcinomas
2) Glioblastomas
It is associated w/ Cowden syndrome
What is the normal fxn of Bel-2?
It is an inhibitor of apoptosis
What is the method of activation of Bel-2?
Often a translocation of bcl-2 gene adjacent to a more heavily used gene, such as the Ig heavy chain gene
What is the consequence of activation of Bel-2?
Increased production of bcl-2
Increased production of bcl-2 results to what?
It results in inhibition of apoptosis
What is the associated neoplasm w/ Bel-2?
Follicular lymphoma
What is the normal fxn of p53?
It promotes production of Bax
What is Bax?
It is a proapoptotic gene
What is the consequence of mutation of p53?
Less p53 results in less Bax
Less p53 w/c results in less Bax results to what?
It results to an indirect cause of inhibition of apoptosis
What is the process / general morphology of cancer development in epithelial cells?
Normal cells -> hyperplasia -> dysplasia -> in situ carcinoma -> invasive carcinoma -> metastatic carcinoma
What is hyperplasia?
It is the increase in the # of normal cells
What is dysplasia?
It is the disorganized cell growth
What are the characteristics of dysplasia?
1) There are cells having hyperchromasia
2) There are mitotic figures present
3) There is an increased nuclear to cytoplasmic ratio
What is the characteristic of in situ carcinoma?
Dysplastic changes throughout the full thickness of the epithelium w/ no evidence of invasion
What is the event present in invasive carcinoma?
Tumor cells invading through the basement membrane
What is the event present in metastatic carcinoma?
Tumor cells spreading to distant organs
What are tumor Ags?
These are Ags that are sp for the tumor
What is the action of tumor Ags?
These can provoke an inflammatory response
*What are the mechanisms of production?
1) Product of mutated oncogene or tumor suppressor gene
2) Protein produced by oncogenic virus
3) Altered cell surface glycoprotein / glycolipid
4) Overexpressed protein
5) Oncofetal Ags
6) Cell-type-specific differentiated Ag (such as expression of CD10)
What are the methods of evading detection by immune system?
1) Growth of Ag-negative variant
2) Apoptosis of cytotoxic T cells through production of FAS ligand
3) Immunosuppression
4) Loss of MHC molecule
What are the type of methods utilized for the dx of neoplasms?
Noninvasive methods
What is the fxn of noninvasive methods in terms of dx of neoplasms?
To detect neoplasms at an early point in their development
What is the importance of utilizing noninvasive methods to detect neoplasms at an early point in their development?
These are crucial to improve the prognosis
What is the action of neoplasms?
These secretes tumor markers into the blood
True or False
Tumor markers are not proteins
False, because tumor markers are proteins
Since the action of neoplasms is to secrete tumor markers, what are the results / uses of this action?
1) It allows for the dx of the tumor or
2) For monitoring of the tumor following treatment
True or False
Metastatic nodules, poorly differentiated neoplasms, and as well as those sharing histologic features may be difficult to be diagnosed microscopically
True
What is crucial for pt care in cases of metastatic nodules?
Determining the site of origin
What is immunohistochemistry?
It is a specialized form of histology employing Abs to identify sp proteins within the tumor to allow for better differentiation of tumor type
*What are the results of dx of neoplasms depending on the differentiation of the tumor?
1) Well differentiated
2) Moderately differentiated
3) Poorly differentiated
What is grade?
It is the differentiation of a tumor as determined by the patho (i.e., subjective evaluation)
What is differentiation?
It is how similar the tumor cells look when compared w/ the cell type of origin
Provide an ex of differentiation
Well-differentiated squamous cell carcinoma looks very similar to stratum corneum, and poorly differentiated squamous cell carcinoma may be difficult to determine w/out immunohistochemical stains directed against squamous cell-specific proteins
What is stage?
It is the extent of the tumor based upon both objective pathologic and objective clinical criteria
What is the most common system used in terms of the principle of grade and stage?
TNM
What does TNM stands for?
T - tumor characteristics
N - lymph node status
M - metastases
What is the characteristic of stage of the tumor?
It has good prognostic value
