neoplasia2

这是一篇关于neoplasia2的思维导图，Passenger mutations’ do not have effect on key pathways or fall in non-coding regions (which may also be important)。

neoplasia

• Grading and staging of cancer
  • 为了正确诊断癌症，实施最适当的治疗并做出预后，必须考虑两个重要参数:
    • Grade of a tumour
    • Stage of a tumour
  • The grading of cancer attempts to establish some estimate of its aggressiveness or level of malignancy based on the cytological differentiation of tumour cells and the number of mitoses within the tumour，Tumours may be classified as grade I, II, III or IV in order of increasing anaplasia (the lesser differentiated, the higher grading),Grading is determined by cytological appearance of the cells
  • Staging of cancers is based on the size of the primary lesion, its extent to spread to regional lymph nodes and the presence or absence of metastases，Staging is usually assessed by the TNM system (T= size of the tumour, N= regional lymph node involvement, M= presence or absence of metastases)，Staging can also be assessed by the AJC method
    • The TNM system
      • T1, T2, T3 and T4 describe the increasing size of the tumour
      • N0, N1, N2 and N3 indicate progressively advancing node involvement
      • M0, M1 reflects the absence or presence of distant metastases, respectively
    • AJC method
      • The AJC method may also be used, which incorporates the size of the primary lesions and the presence of nodal spread and of distant metastases,According to AJC, cancers are divided in stages 0-IV
  • Staging assessment is usually based on clinical and radiological examination (computed tomography and magnetic resonance imaging) and on surgical examination in some cases
• Laboratory diagnosis of cancer
  • Tumour diagnosis is reached based on morphological, clinical, radiological and molecular analyses,实验室诊断关键取决于要检查的标本有多好,The specimen must be adequate, representative and properly conserved
  • Sampling a tumour: 1.Paraffin embedding,几个取样的方法
    • Excision and biopsy refer to the removal of the entire lesion or to part of it, respectively
    • The sample can then be frozen and analysed or fixed and embedded in paraffin
    • Slides are then cut and then stained to look at cell morphology
  • Tumour sampling: 2.Fine needle aspiration
    • Fine needle aspiration involves aspiration of cells from a mass, followed by cytological examination of the smear
    • Especially used for palpable masses affecting breast, thyroid,lymph nodes and salivary glands
• Tumour markers
  • Detection of protein expression in tissues: Immunohistochemistry
    • Immunohistochemistry (IHC) allows the identification of a protein within a tissue, based on the use of a specific antibody,It is not a quantitative technique, but it is very useful as it detects the localisation of protein expression within a tissue,Specific tumour markers can be detected by immunohistochemistry
  • Flow cytometry
    • Flow cytometry relies on the use of fluorescent antibodies against a specific antigen
    • In tumour diagnosis may be particularly useful to detect surface molecules and differentiation antigens to obtain the phenotype of malignant cells
      • Detection of specific antigens
      • Detection of abnormal cells based on DNA quantity
  • Biochemical assays for tumour-associated enzymes, hormones and other tumour markers in the blood can be useful as screening tests,Tumour markers may be helpful to quantitate the response to therapy,Tumour markers can be evaluated to detect tumour recurrence
  • Examples of tumour markers: PSA
    • PSA (prostate-specific antigen) is used for prostatic adenocarcinoma screening,Prostatic adenocarcinoma may be suspected when elevated levels of PSA are found in the blood.PSA level also rises in tumour recurrence following treatment,PSA level may also be high in benign prostatic hyperplasia, so screening tests must be confirmed
  • CEA and a-fetoprotein甲胎蛋白
    • Carcinoembryonic antigen (CEA)and a-fetoprotein are embryonic markers that are not usually expressed in the adult life，Some tumours express CEA (carcinomas of colon, pancreas, stomach, breast) and afetoprotein (hepatocellular carcinomas)，These proteins may be used to detect tumour presence or recurrence after a treatment, but lack definite specificity
  • Hormones: (Paraneoplastic syndromes)，Oncofetal: AFP, CEA，Isoenzymes: PAP, NSE，Proteins: PSA, PSMA (“M” =“membrane”)，Glycoproteins: CA-125, CA-195, CA-153，Molecular: p53, RAS。These can be measured in the blood AND can also be stained in tissue by immunochemical methods
• Molecular diagnosis of cancer and its application
  • Molecular pathology
    • 5 Molecular techniques can be used for:
      • Diagnosis of malignancies
        • The expression of specific tumour markers can be assessed by PCR (i.e. detection of the BCR-ABL fusion product in CML)，FISH can detect the presence of specific tumour abnormalities (i.e. chromosomal translocations as in Burkitt lymphoma)
      • Prognosis and behaviour
        • Certain genetic alterations are associated with a poor prognosis and the identification of these may influence therapy，FISH and PCR may be used to detect HER2/NEU amplification in breast cancer and MYCN amplification in neuroblastoma
      • Detection of minimal residual disease
        • Detection of minimal residual disease can be achieved by PCR to asses the efficacy of treatment,BCR-ABL transcript should disappear following treatment for CML,Detection of this transcripts indicates that tumour cells are still present
      • Diagnosis of hereditary predisposition to cancer
        • Germ-line mutations of several tumour suppressor genes, such as BRCA1 and BRCA2, can increase the risk for developing certain tumours,Detection of these mutations may allow to devise an aggressive screening protocol as well as to choose a prophylactic surgery对这些突变的检测可以设计出一种积极的筛查方案，以及选择预防性手术,Detecting a BRCA mutation may lead to a prophylactic mastectomy
      • Therapeutic decision-making
        • The identification of specific mutations may lead to ‘tailored therapy定制的治疗，The BRAF gene may harbor a mutation in amino acid 600 (the V600E mutation), which renders tumours well-responders to a specific treatment(PLX4032)，This mutation was originally identified in melanomas, but it’s now been found also in other tumours, which can be treated using the same drug
• Molecular profile分子分析 of tumours
  • Molecular profiling of tumours may be done both at the RNA and the DNA levels，The expression level of genes within a tissue may be analysed by microarrays, that analyse the mRNA quantity by using specific fluorescent dyes
  • Thousands of genes identified from tumours give the cells their own identity and fingerprint and may give important prognostic information as well as guidelines for therapy
  • Whole genome sequencing
    • Whole genome sequencing allows the identification of all the alterations (somatic and inheritable) that are present within a genome，This method allows the identification of mutated genes that can be used as targets for tailored therapies
  • Driver and passenger mutations
    • ‘Driver mutations’ affect genes involved in cell proliferation, differentiation and homeostasis
    • Passenger mutations’ do not have effect on key pathways or fall in non-coding regions (which may also be important)
    • Some of these mutations are responsible for drug-resistance