General Pathology: Oncology and Molecular Pathology

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Questions and Answers

What is the primary goal of classification in pathology?

To determine the role of genetic alterations in pathological processes

To identify the specific DNA mutations in tumor pathology

To analyze nucleic acids in patient material

To determine therapy and prognosis (correct)

What is the significance of molecular analysis in cancer diagnosis?

It is used to confirm diagnosis and determine treatment options (correct)

It is used to identify specific stainings in histology

It is used to identify germline aberrations in patient material

It is used to analyze nucleic acids in patient material

What is the challenge in analyzing tissue in molecular pathology?

The quality of the tissue is always optimal

The tissue is always freshly obtained

The quality of the tissue is not always optimal, it may be formalin fixed, partly necrotic and contaminated with non-diseased tissue (correct)

The tissue is rarely contaminated with non-diseased tissue

What is the concept of personalized medicine based on?

Specific genetic aberrations in the diseased tissue Signup and view all the answers

What is the role of immunohistochemistry in classical pathology?

To express proteins as detected by immunohistochemistry Signup and view all the answers

What is the significance of DNA/RNA testing in molecular pathology?

It is used to confirm diagnosis and determine treatment options Signup and view all the answers

What is the purpose of tumor classification in oncology?

To determine therapy and prognosis Signup and view all the answers

What is the significance of histological examination in classical pathology?

It is used to identify morphological changes of histology Signup and view all the answers

What is the primary focus of the study of pathology?

The study of functional and structural changes in cells, tissues, and organs that cause disease Signup and view all the answers

What is the term for the study of the cause of a disease?

Etiology Signup and view all the answers

What is the term for the study of tissue?

Histology Signup and view all the answers

What is the primary goal of molecular analyses in pathology?

To obtain a robust and reliable conclusion Signup and view all the answers

What is the term for the study of the mechanism of development of a disease?

Pathogenesis Signup and view all the answers

What is the term for the relation between the disease and the clinical picture?

Clinical significance Signup and view all the answers

What is the primary focus of the study of cytology?

The study of cells Signup and view all the answers

Which of the following detection methods is used to study the structure of cells and tissues?

Electron microscopy Signup and view all the answers

What is the meaning of M0 in the context of distant metastasis?

Cancer has not spread to other parts of the body Signup and view all the answers

What is aneuploidy?

The presence of an abnormal number of chromosomes in a cell Signup and view all the answers

What is a pathogenic variant in the context of molecular pathology?

A driver mutation in an oncogene Signup and view all the answers

What is the result of a gain of parts of chromosomes/focal in molecular pathology?

Genomic instability Signup and view all the answers

What is the purpose of identifying oncogenes in molecular pathology?

To identify therapeutic targets Signup and view all the answers

What is the result of amplification in copy number variations?

Activating Signup and view all the answers

What is the result of a loss of inhibitory domain in gene rearrangements?

Activating Signup and view all the answers

How is abnormal activation of a proto-oncogene achieved?

By activation of 1 allele Signup and view all the answers

Study Notes

Introduction to Pathology

Determining the correct diagnosis of a disease relies on clear classification, which is the core of pathology.
A correct classification is crucial to determine therapy and prognosis.
Classical pathology deals with morphological changes of histology, specific stainings, and expression of proteins as detected by immunohistochemistry.

Molecular Pathology

The analysis of nucleic acids is integrated in regular pathology diagnostics and is used to confirm diagnosis and determine treatment options.
Molecular analysis is of particular importance in the diagnosis and treatment of cancer.
Classification of tumors is performed using histological examination, location in the body, and identification of specific DNA mutations.
The quality of the tissue is not always optimal, which may be formalin fixed, partly necrotic, and contaminated with non-diseased tissue.

Distant Metastasis (M)

MX: Metastasis cannot be measured.
M0: Cancer has not spread to other parts of the body.
M1: Cancer has spread to other parts of the body.

Molecular Profile Tumor DNA

Copy Number Variation > Genomic Instability

Gain or loss of chromosomes, resulting in aneuploidy and nuclear hyperchromasia.
Gain or loss of parts of chromosomes/focal.

Nucleotide Variation

Single Nucleotide Polymorphism (SNP), silent variation.
Variants with unknown significance (VUS).
Pathogenic variants: driver mutations in oncogene, frameshift/non-sense mutations in tumor-suppressor genes, and passenger mutations.

Genomic Alterations

Nucleotide variations: single nucleotide polymorphism, frameshift variants, or in-frame deletions of insertions.
Pathogenic variants: activating or inactivating.
Variants with unknown significance (VUS).
Copy number variations: amplification (activating), deletion (inactivating).
Gene rearrangements: fusion genes (activating), loss of inhibitory domain (activating).

Oncogenes: Therapeutic Targets

Activation of proto-oncogene > abnormal activation > cancer.
Proto-oncogenes are dominant on a cellular level, and abnormal activation is achieved with activation of 1 allele.

Activities

Study the reading list in advance.
Perform the SSA-test (Brightpace) before attending the work group.
Keep your course book (Robbins and Cotran Pathologic Basis of Disease) available during the work group.
The work group is on campus with a tutor.

Reading List and Study Guidelines

Read the indicated pages from Robbins and Cotran Pathologic Basis of Disease, 10th edition, 2020.
Chapter 5, page 180-187, molecular genetic diagnosis.
Chapter 7, page 267-338, chapter 7: neoplasia.

Molecular Pathology: R-Assignment

Develop an application in R for the analysis of next generation sequencing data.

General Pathology: Introducing Pathology

Pathology = study of disease (study of functional and structural changes in cells, tissues, and organs that cause disease).
Histology = tissue.
Cytology = cells.
Etiology = cause.
Pathogenesis = mechanism of its development.
Morphologic and molecular changes = structural alterations induced in cells and organs of the body.
Clinical significance = relation to the clinical picture.

Detection Methods

Standard histology (such as HE staining).
Special stains (such as histochemical stains and immunohistochemical stains).
Molecular assays.
Electron microscopy.