General Neoplasia Flashcards
Nodules of cancer frequently display central necrosis (umbilication). Causes of tumor cell death in situ include 1. apoptosis 2. ischemia 3. paucity of nutrients 4. vulnerability to host defenses
Causes of tumor cell death in situ include 1. apoptosis 2. inadequate blood supply & ischemia 3. a paucity of nutrients 4. vulnerability to specific and non-specifc host defenses
_____ is a tumor marker for
- adenocarcinomas of the colon
- malignant tumors of the pancreas, lung, and ovary
CEA is a tumor marker for
- adenocarcinomas of the colon
- malignant tumors of the pancreas, lung, and ovary
Neuroendocrine tumors can be identified by their content of _____.
Neuroendocrine tumors can be identified by their content of chromogranins.
_____ is expressed by hepatocellular and yolk sac tumors.
AFP is expressed by hepatocellular and yolk sac tumors.
Chorionic gonadotropin is secreted by ___carcinomas.
Chorionic gonadotropin is secreted by choriocarcinomas.
Tumor marker for soft tissue sarcomas. An intermediate filament.
Vimentin
Tumor marker for soft tissue sarcomas. An intermediate filament.
Malignant lymphomas are generally positive for _____.
Malignant lymphomas are generally positive for leukocyte common antigen (LCA).
Hypermethylation is an example of _____ modification.
Hypermethylation of many _____ _____ and _____ _____ genes has been demonstrated in human tumors, including the p53 pathway.
Unlike genetic changes in cancer, epigenetic changes are reversible.
Hypermethylation is an example of epigenetic modification.
Hypermethylation of many tumor supressor and DNA repair genes has been demonstrated in human tumors, including the p53 pathway.
Unlike genetic changes in cancer, epigenetic changes are reversible.
_____ are benign tumors composed of tissues from all three primary germ layers: ectoderm, mesoderm, endoderm.
They are most common in the ovary, testis, and extragonadal sites.
They contain a variety of structures – skin, neurons, glial cells, cartilage, glandular epithelium.
Teratomas are benign tumors composed of tissues from all three primary germ layers: ectoderm, mesoderm, endoderm.
They are most common in the ovary, testis, and extragonadal sites.
They contain a variety of structures – skin, neurons, glial cells, cartilage, glandular epithelium.
_____ are malignant tumors that harbor embryonal carcinoma stem cells.
Teratocarcinomas are malignant tumors that harbor embryonal carcinoma stem cells.
Localized, disordered differentiation during embryonic development results in a _____, a disorganized caricature of normal tissue components such as cartilage, blood vessels, lymphoid tissue, ducts or bronchi.
Localized, disordered differentiation during embryonic development results in a hamartoma, a disorganized caricature of normal tissue components such as cartilage, blood vessels, lymphoid tissue, ducts or bronchi.
Cancer Epidemiology - what country is associated with each cancer?
Stomach cancer: _____
Colorectal cancer: _____
Prostate cancer: _____
Cancer Epidemiology
Stomach cancer: Japan
Colorectal cancer: United States
Prostate cancer: American blacks
Disease: _____ _____
- autosomal recessive
- increased sensitivity to UV radiation
- pyrimidine dimers
- high incidence of skin cancer
- germline mutations in gene encoding nucleotide excision repair enzyme
Xeroderma Pigmentosum
- autosomal recessive
- increased sensitivity to UV radiation
- pyrimidine dimers
- high incidence of skin cancer
- germline mutations in gene encoding nucleotide excision repair enzyme
Li-Fraumeni syndrome
Germline mutations of _____ lead to inherited predisposition to develop cancers in many organs. The gene functions in transcriptional regulation.
Li-Fraumeni syndrome
Germline mutations of p53 lead to inherited predisposition to develop cancers in many organs. The gene functions in transcriptional regulation.
_____ _____
- mutation in ATM gene, which codes for a nuclear phosphoprotein involved in cell cycle regulation and DNA repair
- cerebellar degeneration
- immunologic abnormalities
- predisposition to cancer
Ataxia telangiectasia
- mutation in ATM gene, which codes for a nuclear phosphoprotein involved in cell cycle regulation and DNA repair
- cerebellar degeneration
- immunologic abnormalities
- predisposition to cancer
Most common causes of death from cancer in women:
- _____
- _____
Most common causes of death from cancer in women:
- Lung cancer
- Breast cancer
_____-_____ anemia is common in cancers that bleed into the GI tract, such as colorectal cancer.
Iron-deficiency anemia is common in cancers that bleed into the GI tract, such as colorectal cancer.
c-abl protooncogene on chromosome 9 t(9,22) –> _____ _____ _____
c-abl protooncogene on chromosome 9 t(9,22) –> chronic myelogenous leukemia
Neuroblastomas
small cell carcinoma of the lung
Wilms tumor
hepatoblastoma
are all associated with gene amplification of _____-family protooncogenes
Neuroblastomas
small cell carcinoma of the lung
Wilms tumor
hepatoblastoma
are all associated with gene amplification of myc-family protooncogenes
Breast cancer and Ovarian cancer are associated with gene amplification of the Erb2 or ___/___ protooncogene
Breast cancer and Ovarian cancer are associated with gene amplification of the Erb2 or HER2/neu protooncogene
C-sis protooncogene encodes _____
–associated with sarcomas and glioblastomas when it is constitutively expressed.
C-sis protooncogene encodes PDGF
–associated with sarcomas and glioblastomas when it is constitutively expressed.
_-___ encodes a receptor for HGF.
Point mutations in _-___ are involved in papillary renal cancers.
C-met encodes a receptor for HGF.
Point mutations in c-met are involved in papillary renal cancers.
Germline point mutations in _-___ are associated with
- multiple endocrine neoplasia (MEN) syndromes
- familial medullary thyroid carcinoma
Germline point mutations in c-ret are associated with
- multiple endocrine neoplasia (MEN) syndromes
- familial medullary thyroid carcinoma
Gastrointestinal tumors (GISTs)
Germline mutations in _-___ .
GISTs
Germline mutations in c-kit
[t(5;12)] generates a fusion protein between the PDGF receptor and another motif, resulting in _____ _____.
t(5;12) generates a fusion protein between the PDGF receptor and another motif, resulting in myelomonocytic leukemia.
DNA viruses and cancer
HPV - _____ cancer
EBV - _____ lymphoma; _____ carcinoma
DNA viruses and cancer
HPV - cervical cancer
EBV - Burkitt lymphoma and Nasopharyngeal carcinoma
_____ benign smooth muscle tumors of the uterus.
Leimyomas are benign smooth muscle tumors of the uterus.
A _____ is a benign mesenchymal tumor of the left atrium.
A myxoma is a benign mesenchymal tumor of the left atrium.
_____
Tumor marker for T-cell malignancies.
CD4
Tumor marker for T-cell malignancies.
HMB-45, S-100 protein
Tumor markers for _____ _____.
HMB-45, S-100 protein
Tumor markers for malignant melanoma.
_____
Tumor marker for muscle tumors.
Desmin
Tumor marker for muscle tumors.
_____
Tumor marker for medullary carcinoma of the thyroid.
Calcitonin
Tumor marker for medullary carcinoma of the thyroid.
Routes of _____ _____.
- Hematogenous
- Lymphatic
- Seeding of body cavities
Routes of tumor metastasis
- Hematogenous
- Lymphatic
- Seeding of body cavities
A malignant tumor of epithelial origin is a _____
A malignant tumor of mesenchymal origin is a _____
A malignant tumor of epithelial origin is a carcinoma
A malignant tumor of mesenchymal origin is a sarcoma
Secondary descriptors of tumor morphologic appearance
_____ : frondlike structure
_____ : dense fibrous stroma
_____ intraductal neoplasm in which necrotic material can be expressed from ducts
Secondary descriptors of tumor morphologic appearance
papillary : frondlike structure
scirrhous or desmoplastic : dense fibrous stroma
comedocarcinoma: intraductal neoplasm in which necrotic material can be expressed from ducts
The definition of a benign tumor resides in its inability to _____ adjacent tissues and to _____.
The lining epithelium of a benign tumor resembles that of the normal tissue.
The definition of a benign tumor resides in its inability to invade adjacent tissues and to metastasize.
The lining epithelium of a benign tumor resembles that of the normal tissue.
Histologic Features of Malignancies
_____ - lack of differentiated features
abundant mitotic activity
disorganized and random growth pattern
invasion of blood vessels and lymphatics
metastases
Histologic Features of Malignancies
anaplasia - lack of differentiated features
abundant mitotic activity
disorganized and random growth pattern
invasion of blood vessels and lymphatics
metastases
Tumor markers for cancers
nuclear receptors for estrogen, progesterone : _____
Lewis a antigen (CA 19-9): _____ and _____
CA 125: _____
Tumor markers for cancers
nuclear receptors for estrogen, progesterone : breast
Lewis a antigen (CA 19-9): pancreatic and gastrointestinal
CA 125: ovarian
carcinoma that does not penetrate the basement membrane
Carcinoma in situ
carcinoma that does not penetrate the basement membrane
Invasion and Metastasis are Multi-Step Events
- Invasion of the basement membrane
- Movement thru extracellular matrix
- Penetration of vascular or lymphatic drainage
- Survival and arrest within circulating blood or lymph
–passage through ECM, invade thru BM–
- Survival and growth as a metastasis (requires angionesis)
Adhesion Molecules
__________
transmembrane receptors that mediate cell-matrix and cell-cell attachment, and stimulate intracellular signaling and gene expression
Adhesion Molecules
Integrins
transmembrane receptors that mediate cell-matrix and cell-cell attachment, and stimulate intracellular signaling and gene expression
Adhesion Molecules
_____ and _____
- suppress invasion and metastasis
- decreased expression in most carcinomas, leading to mestases
Adhesion Molecules
E-cadherin and Catenins
- suppress invasion and metastasis
- decreased expression in most carcinomas, leading to mestases
Malignant cells make proteolytic enzymes that help degrade the basement membrane.
Examples
1.
2.
Malignant cells make proteolytic enzymes that help degrade the basement membrane.
Examples
- u-Pa (urokinase-type plasminogen activator, which converts plasminogen to the protease, plasmin)
- MMPs
FGF, VEGF, TGF-beta, and PDGF all stimulate
_____ _____
FGF, VEGF, TGF-beta, and PDGF all stimulate
tumor angiogenesis
The fate of foci of cancer micrometastases
The fate of foci of cancer micromestases
Cancer _____ reflects cellular characteristics, like organization and cytology.
Cancer _____ refers to the extent of spread.
Cancer grading reflects cellular characteristics, like organization and cytology.
Cancer staging refers to the extent of spread.
T : size of primary tumor N : regional node metastases M : presence and extent of distant metastases
Monoclonal Origin of Cancer: cancers arise from a single transformed cell
Monoclonal Origin of Cancer
Tumor Heterogeneity and Clonal Evolution
Tumor Heterogeneity and Clonal Evolution
Tumor Heterogeneity and Cancer Stem Cells
Tumor Heterogeneity and Cancer Stem Cells
An oncogenic stimulus to a stem or progenitor cell may lead to an expanded pool of transformed stem/progenitor cells. If a transformed cell reacquires a program of self-renewal, the resulting transformed cell may become a cancer stem cell.
Tumor Heterogeneity and Epigenetic Cancer Cell Plasticity
Tumor Heterogeneity and Epigenetic Cancer Cell Plasticity
Epigenetic changes in cell populations may lead to tumor progression or cell death.
Regulation of the Cell Cycle
Regulation of the Cell Cycle
Some rare malignant clones have ______ ______, thereby avoiding senescence and leading to cell immortalization.
Some rare malignant clones have activated telomerase, thereby avoiding senescence and leading to cell immortalization.
Gene: MSH
Function?
Syndrome?
Predominant malignancies?
Carcinomas: _____ / _____ / _____ / _____
Other cancer: _____ _____
Gene: MSH
Function: DNA repair
Syndrome: HNPCC/Lynch Syndrome
Predominant malignancies:
** carcinomas [colon, endometrium, ovary, and bladder]
malignant melanoma**
3 Mechanisms of Genetic Instability in Neoplasms
- _____ instability
- _____ instability
- aberrant ___ _____
3 Mechanisms of Genetic Instability in Neoplasms
- chromosomal instability
- microsatellite instability (secondary to abnormal DNA mismatch repair)
- aberrant DNA methylation
NORMAL human genes involved in cellular growth regulation, proliferation, gene expression
_______
MUTANT versions of these genes
_______
NORMAL human genes involved in cellular growth regulation, proliferation, gene expression
Proto-Oncogenes
MUTANT versions of these genes
Oncogenes
_____ _____
c-myc is a protooncogene on chromosome ___
t(8,14) results in c-myc activation and constitutive expression
(overproduction of normal gene product)
This leads to emergence of a dominant clone of B cells, driven relentlessly to proliferate
Burkitt’s Lymphoma
c-myc is a protooncogene on chromosome 8
t(8,14) results in c-myc activation and constitutive expression
(overproduction of normal gene product)
This leads to emergence of a dominant clone of B cells, driven relentlessly to proliferate
The activation of the ___ proto-oncogene is the most frequent dominant mutation in human cancers.
The activation of the **ras **proto-oncogene is the most frequent dominant mutation in human cancers.
The two-hit origin of retinoblastoma: The tumor suppressor Rb gene on chromosome 13.
The function of Rb genes is a critical checkpoint in the cell cycle, and ______ mutations in Rb permit unregulated cell proliferation.
The two-hit origin of retinoblastoma: The tumor suppressor Rb gene
The function of Rb genes is a critical checkpoint in the cell cycle, and inactivating mutations in Rb permit unregulated cell proliferation.
*Loss of Heterozygosity*
Susceptibility to retinoblastoma is inherited in a _______ fashion because it is the heterozygote that develops the disease.
But the genetic defect in the tumor itself is _______.
Susceptibility to retinoblastoma is inherited in a dominant fashion because it is the heterozygote that develops the disease.
But the genetic defect in the tumor itself is recessive.
The p53 tumor suppressor gene is the principal mediator of growth arrest, senescence, and apoptosis.
Most human cancers display either
1) inactivating mutations of p53
2) abnormalities in the proteins that regulate p53 activity, such as _____ and _____.
The p53 tumor suppressor gene is the principal mediator of growth arrest, senescence, and apoptosis.
Most human cancers display either
1) inactivating mutations of p53
2) abnormalities in the proteins that regulate p53 activity, such as MDM2 and ARF (p14)
Syndrome: familial adenomatous polyposis
Gene: ___
Protooncogene or Tumor Suppressor?
Predominant cancer: ________
Syndrome: familial adenomatous polyposis
APC
Tumor Suppressor Gene
Colorectal carcinoma
Gene: WT1
Predominant malignancies: _____ ; ______
Gene: WT1
Predominant malignancies: Wilms tumor, AML
Gene: BRCA1, BRCA2
Oncogene or Tumor Suppressor?
Predominant cancers: _____, _____
Gene: BRCA1, BRCA2
Tumor Suppressor
Predominant cancers: breast, ovarian
Syndrome: Cowden syndrome
Gene: _____
Oncogene or Tumor Suppressor?
Predominant malignancies: _____, _____, _____
Syndrome: Cowden syndrome
Gene: PTEN
Tumor Suppressor
Predominant malignancies: colorectal, breast, thyroid
*PTEN is an important suppressor of sporadic (non-hereditary) tumor development.
Syndrome: Neurofibromatosis type 1
Gene: ___
Oncogene or Tumor Suppressor?
Predominant malignancies: _______ sarcomas
Syndrome: Neurofibromatosis type 1
Gene: NF-1
Tumor Suppressor
Predominant malignancies: neurogenic sarcomas
Syndrome: Von Hippel-Lindau
Gene: ___
Oncogene or Tumor Suppressor?
Predominant malignancy: _______
Syndrome: Von Hippel-Lindau
Gene: VHL
Tumor Suppressor
Predominant malignancy: renal cell carcinoma
Most cancers display global _____methylation compared to normal tissue.
Most cancers display global hypomethylation compared to normal tissue.
_____-_____ _______
Process by which malignant epithelial cells adopt a disguise as single, nonpolarized, mobile mesenchymal cells. This process is facilitated by loss of E-cadherin.
Epithelial-Mesenchymal Transition
Process by which malignant epithelial cells adopt a disguise as single, nonpolarized, mobile mesenchymal cells. This process is facilitated by loss of E-cadherin.
Viruses and Cancer
HBV and HCV - _____ carcinoma
HHV 8 - _____ _____
DNA Viruses and Cancer
HBV and HCV - Hepatocellular carcinoma
**HBV = hepatitis B virus (DNA virus)
HCV = hepatitis C virus (RNA virus)
HHV8 - Kaposi sarcoma
HHV8 is also implicated in “primary effusion lymphoma” and “multicentric Castleman disease”
HHV8 = human herpes virus 8
RNA retrovirus and Cancer
HTLV-I : ____ leukemia/lymphoma
RNA retrovirus and Cancer
HTLV-I : T-cell leukemia/lymphoma
HTLV-I = human T-cell leukemia virus type 1
Oncogenic DNA viruses have genes that encode protein products that bind to and inactivate the products of _____ _____ _____.
Oncogenic DNA viruses have genes that encode protein products that bind to and inactivate the products of tumor suppressor genes.
The most common neoplasm associated with AIDS is _____ _____.
The virus associated with this cancer is _____.
The most common neoplasm associated with AIDS is Kaposi sarcoma.
The virus associated with this cancer is HHV 8.
Chemical Carcinogens
PVC factory workers : _____ _____
Chemical Carcinogens
PVC factory workers : hepatic angiosarcoma
Chemical Carcinogens
Alkylating agents used in chemotherapy carry a significant risk of _____.
Chemical Carcinogens
Alkylating agents used in chemotherapy carry a significant risk of leukemias.
Chemical Carcinogens
Aflatoxin B1 is a potent _____ carcinogen, and is especially common in parts of Africa and Asia. Aflatoxin B1 is formed in vegetable foods exposed to warm, moist conditions.
Chemical Carcinogens
Aflatoxin B1 is a potent liver carcinogen, and is especially common in parts of Africa and Asia. Aflatoxin B1 is formed in vegetable foods exposed to warm, moist conditions.
Chemical Carcinogens
Occupational exposure to aniline dyes can result in _____ cancer.
Chemical Carcinogens
Occupational exposure to aniline dyes can result in bladder cancer.
Chemical Carcinogens
Nitrosamines may play a role in _____ neoplasms.
Chemical Carcinogens
Nitrosamines may play a role in gastrointestinal neoplasms.
ex: high incidence of esophageal cancer in Hunan province of China due to high dietary content
Chemical Carcinogens
Nickel/Cadmium metals are associated with _____ cancer in factory workers.
Chemical Carcinogens
Nickel/Cadmium metals are associated with lung cancer in factory workers.
Physical Carcinogens
Asbestos causes _____.
Asbestos is widely used in construction, insulation, and manufacturing.
Physical Carcinogens
Asbestos causes mesothelioma.
Tumor-_____ antigens represent somatic mutations or alterations in protein processing, unique to tumor and patient.
Tumor-specific antigens represent somatic mutations or alterations in protein processing, unique to tumor and patient.
Tumor-_____ antigens reflect the production of normal proteins, either in excess or in a setting different from their normal expression. These antigens are recognized as “self” by the immune system, and thus do not lead to effective immune responses.
ex: oncospermatogonial antigens
differentiation antigens
oncofetal antigens
overexpressed antigens
Tumor-associated antigens reflect the production of normal proteins, either in excess or in a setting different from their normal expression. These antigens are recognized as “self” by the immune system, and thus do not lead to effective immune responses.
ex: oncospermatogonial antigens
differentiation antigens
oncofetal antigens
overexpressed antigens
Cancer is often accompanied by an _____ metabolic rate, which may explain the paraneoplastic syndrome of anorexia, weight loss, and cachexia.
Cancer is often accompanied by an evelavted metabolic rate, which may explain the paraneoplastic syndrome of anorexia, weight loss, and cachexia.
Paraneoplastic Syndromes
Cushing Syndrome results from ectopic secretion of _____ by a tumor.
- hypokalemia
- hyperglycemia
- hypertension
- muscle weakness
Paraneoplastic Syndromes
Cushing Syndrome results from ectopic secretion of ACTH by a tumor.
- hypokalemia
- hyperglycemia
- hypertension
- muscle weakness
Paraneoplastic Syndromes
Inappropriate antidiuresis is associated with production of _____.
The tumor that most often produces this syndrome is _________.
Paraneoplastic Syndromes
Inappropriate antidiuresis is associated with production of ADH.
The tumor that most often produces this syndrome is small cell lung carcinoma.
Paraneoplastic Syndromes
The most common cause of hypercalcemia is the secretion of a PTH-like peptide by an _____ tumor, such as small cell lung carcinoma or breast adenocarcinoma.
Paraneoplastic Syndromes
The most common cause of hypercalcemia is the secretion of a PTH-like peptide by an epithelial tumor, such as small cell lung carcinoma or breast adenocarcinoma.
Paraneoplastic Syndromes
Venous thrombosis is usually associated with _____ carcinoma.
Paraneoplastic Syndromes
Venous thrombosis is usually associated with pancreatic carcinoma.
Acanthosis nigricans is frequently associated with _____ carcinomas.
Acanthosis nigricans is frequently associated with gastrointestinal carcinomas, especially stomach cancers.
