Mikrosatelit hotels (short tandem repeats), 2 – 10 nukleotidlik are a recurrent motif that consists of repetitive DNA sequences. Mismatch repair (MMR) genes ( MLH1, PMS2, MSH2, MSH6 ) that defects in DNA synthesis , and mutations in this region are not repaired during mikrosatelit mikrosatelit instability (MSI) causes.

Mikrosatelit instability (MSI) colorectal adenocarcinoma (CRC) is one of the ways that play a role in carcinogenesis; colorectal cancer with msi MSI / mikrosatelit unstable or MMR deficiency (dMMR) colorectal cancer is called with. Mikrosatelit instability (MSI), one or more mismatch repair gene ( MLH1, PMS2, MSH2, MSH6 ) is caused by abnormal function of.

Of colorectal adenocarcinomas (CRC) on 10% – 15% MSI / MMR has deficiency (dMMR). germ line mutations in MMR genes MLH1 in sporadic dMMR colorectal cancer or promotor hipermetilasyon ( Lynch syndrome ) will occur due to.

In pathology, the first of colorectal cancer, immunohistochemistry of MMR proteins by using an evaluation in terms of the presence of MSI is scanned. Loss of one or more MMR proteins, MLH1 BRAF mutation test or the test is followed by hipermetilasyon ; the absence of MLH1 or hipermetilasyon BRAF mutation, Lynch syndrome to assess germ line mutation activates.

for the assessment of dMMR colorectal cancer is important because these tumors mikrosatelit stable (MSS) tumors and thus has better survival compared to the stage of the tumor better. Previously nonpolipozis Lynch syndrome hereditary polyposis colorectal cancer (HNPCC) syndrome was known as.

Constitutional mismatch repair deficiency associated with germ line mutations in a gene that is biallelik MMR is called.

Colorectal cancers 10% – 15% is dMMR ( Clin Cancer Res 2012;18:1506 )

  • dMMR colorectal cancers is about 80% so I
    • Promotor of MLH1 hipermetilasyon
    • ≥ 60 years old
    • F > E
  • dMMR colorectal cancer is about 20% ailesel
    • Autosomal dominant germ line mutations (Lynch syndrome)
    • ~ 40 – 50 between the ages of
    • E = F
dMMR colorectal cancer tend to the right speaker ( Arch Surg 1977;112:170 )
MMR path ( J Gastroenterol 2020;55:15 )
  • During DNA replication, DNA base substitution mismatch (mismatch), additions (insertion), deletions (deletion), or shifts (slippage) corrects
  • The influence of the protein complex is corrected two errors:
    • If MUT: mutS homolog 2 (MSH2) and mutS homolog 6 (MSH6) proteins heterodimer
    • MutSß: and MSH2 mutS homolog 3 (MSH3) proteins heterodimer
  • MutSα veya MutSβ, kusurlu bölgeye bağlanır ve MutLα’yı (mutL homologu 1 [MLH1] ve postmeiotik segregasyon artışı 2 [PMS2] proteinlerinin heterodimeri) devreye sokar.

 

MSS colorectal cancer/enough MMR (pMMR) or MSI/missing MMR (dMMR)
  • pMMR colorectal cancer: solid MMR genes
  • dMMR colorectal cancer: the MMR gene abnormality that affects one or more
    • Sporadic
      • The promoter of the MLH1 hipermetilasyon
      • 50 %BRAF V600E mutation
      • May play a role in the carcinogenesis of ARID1A ( Hum Pathol 2014;45:2430 )
    • Family – Lynch syndrome
      • Subsequent somatic mutation in germ line mutations of the usual type allele
      • MLH1, PMS2, MSH2, MSH6, in EpCAM ( adjacent to MSH2 ) mutations
    • The other:
Lynch syndrome is associated with an increased risk of carcinomas of different organs in.
  • Gastrointestinal: colon, small intestine, gastric, hepatobiliary, pancreatic
  • Genitourinary: renal, bladder, prostate
  • Gynecology: the endometrium, ovary
Clinical evaluation
  • patients with dMMR colorectal cancer may be asymptomatic and discovered incidentally during colonoscopy surveillance may have an audience, while others of the MSS colorectal cancer symptoms (anemia, fatigue, weight loss, or a change in bowel habits hematokez) may show, and this may lead to a colonoscopy.
  • If you have the clinical suspicion of Lynch syndrome, the Amsterdam criteria or the Bethesda system scan can be performed by using:
    • The Amsterdam criteria ( Outer Colon Rectum 1991;34:424 )
      • In the presence of at least 3 relatives with colorectal cancer (1% other 2% first-degree relative)
      • At least 2 successive generation it comes to
      • At least 1 person who is diagnosed with colorectal cancer
      • Familial adenomatous polyposis (fap) are excluded
    • The Bethesda system (revised) ( J Natl Cancer Inst 1997;89:1758 )
      • The diagnosis of colorectal cancer
      • Other Lynch syndrome associated with the presence of colorectal cancer or other tumor
      • MSI-H phenotype in colorectal cancer
      • Associated with Lynch syndrome tumors with 2+ first-or second-degree relatives of colorectal cancer patients
Pathological evaluation (see. diagram 3 )
  • Most institutions will test all colorectal cancer cases in terms of the lack of MMR
    • Immunohistochemistry (IHC): MLH1, PMS2, MSH2, MSH6 IHC markers for
      • The loss of the Token requires one or more additional testing
        • BRAF mutation status (IHC or PCR)
        • MLH1 methylation status
      • The absence of BRAF mutation testing of the germ line or encourages metilasyon
        • Next generation sequencing
    • Specific patterns to look for;
      • MLH1 / PMS2 loss of sporadic favor
      • MSH2 / MSH6 loss of the family in favor of
      • Isolated loss of PMS2: in favor of the family
      • Isolated loss of MSH6: in favor of the family
dMMR colorectal cancer

Mikrosatelit instability (instability) analysis

Sample pathology report

  • Immunhistokimya MSI in colorectal adenocarcinoma or BRAF mutation status should be included in the pathology report of hipermetilasyon for comments. Examples include:
    • MSI (by IHC) comment:
      • pMMR colorectal cancer:
        • Mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 were applied for immunohistochemical paints. Tumor cells, tumor-sufficient in terms of MMR (pMMR) and probably in terms of microsatellite stable, which indicates that the nuclear staining for all four proteins are covered.
      • dMMR colorectal cancer:
        • Immunohistochemical dyes, MLH1 and PMS2 protein expression with loss of tumor incompatible repair deficiency (dMMR) is MSH6 show that MSH2 expression and nuclear are protected. BRAF mutation analysis to determine whether this represents a sporadic type carcinoma (or methylation status) is done.
    • BRAF mutation interpretation:
      • The absence of mutation:
        • BRAF V600E mutation analysis was performed and the mutation was identified. These tests are conducted to evaluate somatic tumor phenotype. tumors may be sporadic dMMR, or Lynch syndrome (hereditary non-polyposis colorectal cancer may be associated with. It is recommended that the program be referred to hereditary cancer screening.
      • The presence of the mutation:
        • Molecular tests demonstrated BRAF V600E mutation, which is associated with the presence of sporadic MLH1 promotor hipermetilasyon . However, if you have a strong family history, BRAF V600E mutations exclude patients on the basis of the germ line should be exercised when scanning from .