Glossary

Adenoma: A benign tumor that arises in or resembles glandular tissue. If it becomes cancerous, it is called an adenocarcinoma.

Allele:  An alternative form of a gene. One of the different forms of gene that can exist at a single locus (spot on a chromosome). Also one of the different forms of any segment of a chromosome.

Allelic imbalance: A state in which one of the two copies of the genome, segments of the genome or genes are present in relative excess compared to the other copy. In normal cells, each allele (see allele) is present as two copies otherwise known as allelic balance. Allelic imbalance results when either there is loss of one of the two copies (genomic deletion) or when one of the two alleles is present in excess amount (genomic amplification). Allelic imbalance is not a normal state and indicates the presence of pre-cancer or cancer.

Allelic loss: Refers to a state in which one of the two copies of the human genome or part of the genome (allele) is lost from the cell in a process of genomic deletion. Generally allelic loss occurs at sites of tumor suppressor genes including adjacent DNA resulting in loss of growth control and conferring on the cell a growth advantage relative to other normal and less affected cells.

Allelic peak heights: The maximal fluorescence generated for a specific allele as measured by capillary electrophoresis.

Ascites:  Abnormal buildup of fluid in the abdomen. Ascites can occur as a result of a number of conditions, including severe liver disease and the presence of malignant cells within the abdomen.

Atypical: Not typical, not usual, not normal, abnormal. Atypical is often used to refer to the appearance of precancerous or cancerous cells.

Biliary strictures: Biliary stricture is an abnormal narrowing of the biliary duct, the tube that moves bile.  Biliary strictures are often caused by surgical injury to the bile ducts, for example, after surgery to remove the gallbladder.

Biopsy: The removal of a sample of tissue for purposes of diagnosis.

B-raf: An important human oncogene involved in many different forms of human cancer including that derived from the large bowel, melanoma and thyroid gland.

Capillary electrophoresis: A technical process wherein fragments of DNA are sorted accorded to their length as a mixture of DNA is caused to move through a porous medium (polyacrylamide) by electrical forces. In essence, DNA is sieved according to individual fragment size.

Carcinoembryonic antigen: Carcinoembryonic antigen (CEA) is a protein found in many types of cells but associated with tumors. The main use of CEA is as a tumor marker, especially with intestinal cancer. The most common cancers that elevate CEA are in the colon and rectum.

Chromosomal deletions: Loss of a defined segment of variable length of a chromosome bearing one or more genes or parts of genes. Chromosomal deletions are the most common cancer associated genetic abnormality.

C-kit: One of the many oncogenes of the genome primarily concerned with the growth regulation. Point mutation of C-kit can contribute to cancer formation. C-kit mutations are especially important in certain forms of human cancer such as chronic myelogenous leukemia, gastrointestinal stromal tumor (GIST), adenoid cystic carcinoma of the salivary gland and other cancers.

Clonal expansion: The process whereby a cell, having acquired a mutational change that significantly enhances growth and proliferation, comes over time to predominantly constitute the largest subset of cells in a given tissue specimen. The growth advantage conferred by the mutation leads progeny cells to become the dominant cell population of a given organ. Cancer involves the successive acquisition of such mutations leading to waves of clonal expansion culminating in malignancy including the properties of invasion and spread to other sites of the body.

Concordant mutations: A series or profile of DNA marker mutations from a given specimen that matches precisely the profile from that of another sample.

Crypts: In anatomy, a crypt is variously a blind alley, a tube with no exit, a depression, or a pit -- in an otherwise fairly flat surface. The words crypt and cryptic come from the Greek "kryptos" meaning hidden or concealed.

Cystadenocarcinoma:  adenocarcinoma characterized by tumor-lined cystic cavities; occurring usually in the ovaries but also in other sites such as the appendix, pancreas, or thyroid.

Cytology: The study of cells, their origin, structure, function and pathology; the microscopic examination of cells as a means of detecting malignancy and microbiologic changes. Cells can be obtained by aspiration, washing, smear or scraping.

DALM: Acronym for dysplasia associated lesion/mass. See dysplasia associated lesion/mass.

Diagnostic test: An assay conducted for diagnostic purposes.

Differentiated: Cells that maintain, in culture, all or much of the specialized structure and function typical of the cell type in vivo.

Discordant mutations: A series or profile of DNA marker mutations from a given specimen that do not match precisely the profile from that of another sample.

Dysplasia: Any abnormal development of tissues or organs. In pathology, alteration in size, shape, and organization of adult cells.

Dysplasia associated lesion/mass: A neoplastic proliferation in the large bowel in patients with chronic inflammatory bowel disease that, unlike more typical tubulovillous adenomas, is not well confined and has a much greater likelihood for progression into malignancy.

Endoscopic: Examination performed by a gastroenterologist wherein a tube is passed through the upper or lower gastrointestinal tract permitting observations, imaging and the taking of biopsy specimens.

Endoscopic ultrasound: A test that uses an endoscope (a flexible tube inserted into the body) to bounce high-energy sound waves off internal tissues and organs and change the echoes into pictures (sonograms). Also called endosonography.

Epithelial: Cells that cover surfaces of the body and its organs and line the cavities of the body.

Epitheloid haemangioendothelioma: A benign tumor derived from cells lining the blood vessels. Epithelioid haemangioendothelioma can occur at any organ or site within the body but is relatively more common in the liver.

Fine Needle Aspirate: Suction is applied to a hollow needle which has been inserted into tissue and a core of the tissue is withdrawn to culture and/or examine microscopically.

Free DNA: DNA that is not present within an intact cell but liberated to float in a fluid medium.

Gene inactivation: A process whereby structural damage to DNA causes a particular gene to fail or function normally and fail to express its protein. Gene inactivation occurs via chromosomal deletion and is most commonly seen in tumor suppressor genes which represent the most common cancer associated abnormality.

Gene silencing: Imprinting, or silencing, is the suppression of certain genes on chromosomes, depending on from which parent they were received. When DNA is passed to daughter cells after fertilization of an egg by a sperm, certain alleles can become active only if they were received from the mother, others only if they came from the father.

Genetic mutation: a change in the nucleotide sequence of a DNA molecule. The term "mutation," is generally used to refer to changes in DNA sequence which are not present in most individuals of a species and either have been associated with disease (or risk of disease) or have resulted from damage inflicted by external agents (such as viruses or radiation).

Genomic loci: A particular point in the human genome localized to a particular location on a chromosome.

Genotyping: The process of screening patients to identify the specific gene and the specific error (mutation) in a gene that causes a disease.

GIST: Acronym for Gastrointestinal Stromal Tumor, a sarcoma or malignancy of soft tissue origin arising anywhere in the gastrointestinal tract.

Glioma: A glioma is a type of primary central nervous system (CNS) tumor that arises from glial cells. The most common site of involvement of a glioma is the brain, but they can also affect the spinal cord, or any other part of the CNS, such as the optic nerves.

Glioma anaplastic: A cancer derived from astrocytes of the central nervous system in which the cells show malignant microscopic characteristics such as large cell size, bizarre nuclear appearance, hypercellularity and increased mitotic activity.

Glioblastoma Multiforme: the most malignant form of cancer derived from astrocytes of the central nervous system. Growth is rapid and survival is poor.

Grade of dysplasia: The degree to which the cells of a particular precancerous growth resemble those of the normal cells from which they share origin. Low grade dysplasia cells resemble closely their normal counterparts. High grade dysplasia cells appear distinctly different from their normal cellular counterparts.

Hepatic parenchymal reserve: Liver cells composing the liver that are not cancer cells.

Hepatocellular carcinoma (HCC): Cancer derived from live cells.

High amplitude mutation: A mutation that is present in greater than 75% of a particular group of cells. High amplitude denotes significant clonal expansion wherein a mutation confers significant growth advantage. High amplitude mutations are present in high grade dysplasia and malignant cell proliferation.

High grade dysplasia: Precancer that is not likely to reverse or regress back into low grade dysplasia or normalcy.

HNPCC: Acronym for Hereditary Non-Polyposis Colon Cancer. Colon cancer that develops as a result of mutation involving one of the cell's DNA repair genes. This mutation can be somatically acquired or inherited being present in the germline.

In situ: In place; localized and confined to one area. A very early stage of cancer.

Indeterminant: A diagnosis rendered by a pathologist that fails to clearly distinguish between two or more diagnostic possibilities that require management and treatment in significantly different ways.

Inflammatory atypia: Non cancerous microscopic changes in cells mimicking the appearance of dysplasia or cancer induced by inflammation but not having any relationship to cancer development. PathFinderTG is able to clearly and definitively discriminate between inflammatory atypia and true dysplasia or cancer.

Inflammatory associated dysplasia: An as yet poorly understood process wherein chronic, longstanding irritation from inflammation and regenerative change leads to cancer formation. It is important to understand when the microscopic changes reflect inflammation and when the transition to neoplasia has taken place.

Intraductal papillary mucinous neoplasia (IPMN): A pancreatic neoplastic process that involves an extended portion of either the main pancreatic duct or its major branches wherein one or more neoplastic cell populations are proliferating generally forming multiple cyst and/or duct dilations.

Intraductal papilloma: Benign, small, non-palpable, tissue growth in the breast duct, frequently causing bleeding from the nipple.

Intraepithelial: Within the layer of cells that form the surface or lining of an organ.

K-ras-2: An important human oncogene involved in many different forms of human cancer including that derived from the large bowel, pancreas, lung, endometrium, ovary and other organ sites.

Lesion: A lesion is a non-specific term referring to abnormal tissue in the body. It can be caused by any disease process including trauma (physical, chemical, electrical), infection, neoplasm, metabolic and autoimmune.

LOH: An abbreviation commonly used for loss of heterozygosity (see "loss of heterozygosity"). Encompasses allelic imbalance and allelic loss.

Loss of herterozygosity (LOH): Synonymous with allelic imbalance, this termed is commonly abbreviated as LOH (see “LOH”). Heterozygosity denotes the presence of two alleles which can be individually discriminated by slight, minor differences in DNA sequence commonly found at microsatellites (see “microsatellite”). In the normal state, the two alleles can be dinstinguished from a each other and are said to exist in a state of heterozygosity. When mutations are acquired which typically involve deletion of all or part of an allele (see “allele”), one of the two copies is lost from the cell by deletion leading to a loss of heterozygosity.

Low amplitude mutation: A mutation that is present in less than 75% of a particular group of cells. Low amplitude denotes mild clonal expansion wherein a mutation does not confer significant growth advantage. Low amplitude mutations are present in low grade dysplasia and benign cell proliferations.

Malignancy: Cancerous growth, a mass of cells showing uncontrolled growth, a tendency to invade and damage surrounding tissues and an ability to seed daughter growths to sites remote from the primary growth.

Meningeal invasion: Spread of cancer to the meningeal space covering the brain and spinal cord.

Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue.

Metachronous: Two or more cancers appearing at different points in time.

Metastatic: Cancer that has spread to other parts of the body from the original tumor site.

Microdissection: The act of removing from a tissue section or cytology slide preparation a predetermined collection of cells situated at a particular site on the slide. This is done under microscopic observation targeting a particular group of cells that may exhibit unique cellular microscopic changes. Microdissection permits the observer to isolate a small but highly representative collection of cells which then undergoes mutational analysis affording the opportunity to tightly correlate cellular changes seen under the microscope with underlying molecular alterations.

Microsatellite instability: A change that occurs in the DNA of certain cells (such as tumor cells) in which the number of repeats of microsatellites (short, repeated sequences of DNA) is different than the number of repeats that was in the DNA when it was inherited. The cause of MSI may be a defect in the ability to repair mistakes made when DNA is copied in the cell.

Microsatallite markers: Segments of DNA composed of variable numbers of short repeat units that occur in predictable locations within the genome but vary in absolute length according ot the number of repeats. Microsatellite markers can be used to evaluate the two different copies or alleles of the human genome

Mucinous cystic neoplasm (MCN): A benign or malignant tumor arising from the mucinous producing cells lining the pancreatic ductal system.

Multifocal independent tumors: Two or more cancers that each arise independently from each other in different locations.

Multiple primary tumor: Two or more cancers that each arise independently from each other in different locations.

Mutation: an irreversible structural change in the normal sequence of DNA that significantly alters the normal functional status of a cell. Mutations can be inherited but more commonly are acquired during life as a result of exposure to harmful chemicals or physical agents which damage DNA. Accumulation of mutations leads to pre-cancer and then to cancer.

Mutational profile: the unique constellation of acquired mutational alterations present in a given cell. The mutational profile is unique to each cancer in the specific pattern of acquired mutations, the specific alleles affected by mutational damage and the temporal sequence of irreversible mutation acquisition over time. The mutational profile can be viewed as a unique dynamically changing fingerprint of a given cancer as it evolves over time.

Neoplasia: The formation of tumors characterized by the presence of new and uncontrolled cellular growth.

Onocogene: A mutation in a gene that causes the cell to lose control of some aspect of growth regulation. Oncogene mutations can affect only one copy of the gene to exert their deregulating effect.

Pancreatic ductal adenocarcinoma: Cancer derived from the cells lining the pancreatic ductal system.

Peritoneal fluid: The small amount of fluid in the peritoneal cavity, which is one of the body's main cavities (it contains the stomach, liver, intestines, and, in women, the uterus and ovaries).

Point mutations: A change in the coding sequence of a gene at one phase that is sufficient to alter the normal function of that gene.

Polymerase chain reaction: A biochemical enzymatic process, performed in the laboratory, wherein a predetermined short segment of the human genome is replicated into many millions of identical copies. Short segments of DNA representing the sites in the genome subject to mutational damage can be copied into sufficient amount to enable their analytical detection, quantification and characterization.

Polymorphic allele pairing: Two alleles that show structural difference in DNA sequence and/or length.

Polyp: A polyp is a smooth-coated abnormal growth (tumor) projecting from a mucous membrane. It is attached to the surface by a narrow elongated pedicle. Polyps are commonly found in the nose, vocal cords, urinary bladder, uterus, rectum, and large intestine. They may also occur elsewhere in the body where mucous membrane exists.

Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous.

Prognosis: Prediction of probable outcome and/or course of a disease.

Pseudo invasion: Microscopic features in tissues that mimic the appearance of an invasive cancer but in fact represent a benign, noninvasive tumor. An example would be a benign colon polyp that has been forced into the bowel wall by the action of the fecal stream. A microscopic section of this abnormality can mimic the appearance of cancer, but PathFinderTG clearly discriminates the true nature of the process.

Pseudocyst: A collection of fluid not lined by a layer or cells. A common example is a pseudocyst of the pancreatitis that forms following an episode of pancreatitis.

Reactive: Reacts easily or readily in some conditions.

Recurrent: Reappearance of cancer cells at the same site or in another location after a disease-free period.

Resection: This is the removal of tissue, a tumor or organ from the body.

Sarcoma:  A malignant tumor growing from connective tissues, such as cartilage, fat, muscle or bone.

Schlerosing cholangitis: An idiopathic (unknown cause) inflammatory process of the biliary tract that can mimic the presence of cancer and itself can lead to the formation of cancer.

Screening test: A test done on apparently healthy people to detect disease before symptoms appear.

Serous cystadenoma: A benign form of pancreatic tumor formation derived from duct lining cells that will not progress into cancer.

Stage: The extent of a cancer, especially whether the disease has spread from the original site to other parts of the body. Staging refers to the determination of the extent of cancer.

Stromal: Relating to the stroma of an organ or other structure, that is, its framework, usually of connective tissue, rather than its specific substance. (SMD)

Suspicious: A term to denote indeterminate diagnosis used by a pathologist when there is a concern that cancer may be present but where non-cancer states cannot be entirely excluded.

Synchronous: Occurring at the same time

Temporal sequence of mutation acquisition: Refers to the multistep process of serial mutation accumulation over time that leads to clonal expansion and cancer formation. The temporal sequence for a given cancer is unique because mutation acquisition is an irreversible process driving the affected cell forward into pre-cancer and then cancer.

True invasion: Cancer invasion of tissue that cannot be accounted for otherwise.

Tubulovillous adenoma: A type of polyp that grows in the colon and other places in the gastrointestinal tract and sometimes in other parts of the body. These adenomas may become malignant (cancerous).

Tumor suppressor genes: The role of tumor suppressor genes is to maintain the integrity of the DNA in cells. The activation of a tumor suppressor gene at certain "check points" puts on the "brakes" and allows the cell to check for any damage in its DNA. Usually repairs are made before the cell is allowed to go on and divide. Without these brakes, cells with damaged DNA would copy the damage and pass damage on to daughter cells. The damage becomes a permanent mutation in future generations of new cells.

Ulceration: The formation of a break on the skin or on the surface of an organ. An ulcer forms when the surface cells die and are cast off. Ulcers may be associated with cancer and other diseases.

Undifferentiated: A term used to describe cells or tissues that do not have specialized ("mature") structures or functions. Undifferentiated cancer cells often grow and spread quickly.

Urothelial tissue: Tissue derived from the urinary bladder.