The most common symptom of endometrial cancer is abnormal vaginal bleeding. In HNPCC, the mean age of diagnosis of gastric cancer is 56 years of age with intestinal-type adenocarcinoma being the most commonly reported pathology. HNPCC-associated ovarian cancers have an average age of diagnosis of 42.5 years-old; approximately 30% are diagnosed before age 40.Significant variation in the rate of cancer has been found depending on the mutation involved. Up to the age of 75 years the risks of different cancers by the mutations are in the table below. Genetics
HNPCC is inherited in an autosomal dominant fashion. The hallmark of HNPCC is defective DNA mismatch repair, which causes an elevated rate of single nucleotide changes and microsatellite instability, also known as MSI-H (the H is "high"). MSI is identifiable in cancer specimens in the pathology laboratory. Most cases result in changes in the lengths of dinucleotide repeats of the nucleobases cytosine and adenine (sequence: CACACACACA...).The 4 main genes involved in HNPCC normally encode for proteins that form dimers to function:

MLH1 protein dimerizes with PMS2 protein to form MutLα, which coordinates the binding of other proteins involved with mismatch repair like DNA helicase, single-stranded-DNA binding-protein (RPA), and DNA polymerases. MSH2 protein dimerizes with MSH6 protein, which identifies mismatches via a sliding clamp model, a protein for scanning for errors.The impairment of either gene for the protein dimer impairs the protein function.
Age-based testing for IHC has been suggested in part due to cost-benefit analyses, whereas universal testing for all people with colorectal cancer ensures people with Lynch Syndrome are not missed. To address the costs, researchers are trying to predict MSI or IHC directly from the way the tumor looks under the microscope, without doing any molecular testing. Microsatellite Instability
Mutations in DNA mismatch repair systems can lead to difficulty transmitting regions within the DNA which contain repeating patterns of two or three nucleotides (microsatellites), otherwise known as microsatellite instability (MSI). MSI is identified through DNA extraction from both a tumor tissue sample and a normal tissue sample followed by PCR analysis of microsatellite regions. MSI analysis can be used to identify people who may have Lynch syndrome and direct them for further testing. Classification
Three major groups of MSI-H (microsatellite instability – MSI) cancers can be recognized by histopathological criteria:
right-sided poorly differentiated cancers
right-sided mucinous cancers
adenocarcinomas in any location showing any measurable level of intraepithelial lymphocyte (TIL)The histopathological criteria are not sensitive enough to detect MSI from histology but researchers are trying to use artificial intelligence to predict MSI from histology.In addition, HNPCC can be divided into Lynch syndrome I (familial colon cancer) and Lynch syndrome II (HNPCC associated with other cancers of the gastrointestinal tract or reproductive system).