Lynch syndrome (LS) is an autosomal dominant hereditary disease caused by deletion of such DNA mismatch repair (MMR) genes as MLH1, MSH2, MSH6, and PMS2. The functional loss of MMR genes results in instability of the highly repetitive DNA sequence, and may eventually leads to tumor occurrence. Here we report a case of LS- related endometrial cancer in a clustered LS family identified by genetic counseling and genetic testing. For patients with a family history of LSrelated tumors, the diagnosis of LS should be considered, and immunohistochemical testing of MMR and genetic testing for LS should be performed. A definite diagnosis of LS has important clinical significance for individuals and family members, and risk screening and preventive measures can minimize the overall risk of developing LS-related cancers.
Colorectal Neoplasms, Hereditary Nonpolyposis/pathology* ; DNA Mismatch Repair ; Endometrial Neoplasms/pathology* ; Female ; Genetic Testing/methods* ; Humans

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited disease associated with germ-line mutations in mismatch repair genes and microsatellite instability. This article reviews the molecular biology and clinical pathology of HNPCC.
Colorectal Neoplasms, Hereditary Nonpolyposis ; diagnosis ; genetics ; pathology ; DNA Mismatch Repair ; Humans ; Microsatellite Instability

BACKGROUND: During specimen processing in surgical pathology laboratories, specimen-related adverse events (SRAEs), such as mislabeling and specimen mixed-up might occur. In these situations, molecular techniques using short tandem repeat (STR) loci are required to identify the personal identity. Microsatellite instability (MSI) test is widely used for screening the hereditary non-polyposis colon cancer (Lynch syndrome) in surgical pathologies using polymorphic STR markers. We tried to evaluate the applicability of the MSI test for SRAEs. METHODS: We obtained 253 MSI test results to analyze the allele frequencies. After calibrating the estimated nucleotide lengths, we calculated the allele frequencies, a random match probability, and a likelihood ratio (LR) of three dinucleotide STR markers (D5S349, D17S250, and D2S123). RESULTS: The distribution of LR was 136.38 to 5,606,213.10. There was no case of LR<100. In addition, there were 153 cases (60.5%) of LR ranging from 100 to 10,000 and 100 cases (39.5%) of LR>10,000. Furthermore, the combined probability of identity was 9.23x10(-4) and the combined power of exclusion was 0.99908. CONCLUSIONS: Using the three STR markers that are recommended for MSI test, all the cases were positively identified in 1% range and about one-third cases showed high LR (>10,000). These results showed that MSI tests are useful to screen the personal identity in case of SRAE in pathology laboratories.
Biometric Identification ; Colonic Neoplasms ; Colorectal Neoplasms, Hereditary Nonpolyposis ; Gene Frequency ; Humans ; Mass Screening ; Microsatellite Instability ; Microsatellite Repeats ; Pathology, Surgical ; Succinimides

OBJECTIVETo analyze the clinical and pathological features of patients with hereditary nonpolyposis colorectal cancer (HNPCC).

METHODSThe data of 8 HNPCC pedigrees according with Amsterdam standard II were collected and their pedigree trees were generated.

RESULTSThe morbidity of HNPCC was 1.59%. Thirty-one patients were found in the 8 HNPCC pedigrees including 25 with colorectal cancer and 6 with extraintestinal tumors. The 8 probands consisted of 6 female and 2 male patients, among whom 4 were younger than 40 years old, 2 had lesions in the right colon, 3 in the left colon, and 3 in the rectum. The tumors were histologically identified mainly as highly to moderately differentiated adenocarcinoma; all the patients were free of lymph node or distant metastasis. Of the 8 probands, 5 had abnormal expression of MMR protein and only 1 had normal expression.

CONCLUSIONThe HNPCC probands are characterized by early onset at a young age and high differentiation of the tumor. The members of the pedigrees show a high incidence of the malignancies, and regular examination and timely treatment can be effective in preventing the tumor occurrence and reducing the mortality. Detection of MMR gene mutation can be a crucial approach to raising the diagnostic rate of HNPCC.

Adult ; Aged ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; pathology ; DNA Mismatch Repair ; genetics ; Female ; Humans ; Male ; Middle Aged ; Pedigree

OBJECTIVETo analyze the mutational features of adenomatous polyposis coli (APC) gene and to explore the effect of mismatch repair (MMR) deficiency on its mutations in hereditary non-polyposis colorectal cancers (HNPCC).

METHODSPCR-based in vitro synthesized protein test (IVSP) assay and sequencing analysis were used to confirm somatic mutations of whole APC gene in 19 HNPCC patients.

RESULTSEleven cases with thirteen mutations were determined. The frequency of APC mutation was 58%(11/19). The exhibiting mutations consisted of 9 frameshift mutations and 4 nonsense ones, indicating the existence of more frameshift mutations (69%). All of frameshift mutations were deletion or insertion of 1-2 bp and most of them (7/9) happened at simple nucleotide repeat sequences, particularly within (A) n tracts (5/9). All of four nonsense mutations resulted from C to T transitions at CpG sites.

CONCLUSIONMutational inactivations of APC gene were detected in more than half of HNPCC patients in this study, indicating that APC mutation is a common molecular event in the tumorigenesis of HNPCC. According to the location of frameshift mutations at simple nucleotide repeat sequences and point mutations at CpG sites, it was suggested that endogenous mechanisms like MMR deficiency might exert an effect on the nature of APC mutations in most HNPCC.

Adenomatous Polyposis Coli ; genetics ; Adenomatous Polyposis Coli Protein ; genetics ; metabolism ; Carcinoma ; genetics ; Colorectal Neoplasms ; genetics ; pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; Genes, APC ; physiology ; Humans

OBJECTIVETo investigate the clinicopathological features of Chinese hereditary nonpolyposis colorectal cancer (HNPCC).

METHODSPatients who met the Amsterdam criteria were enrolled in this study from several hospitals in China. Clinicopathological features of patients with HNPCC were compared between the patients with suspected HNPCC and sporadic colorectal cancer.

RESULTSOne hundred and sixty-seven individuals from 31 families met the Amsterdam criteria. The average age was 48.6 (22-78) years old. There were 43 cases (31.9%) with ascending colon cancer and 52 cases (38.5%) with rectal cancer. The 3-, 5-, 10- years survival rate was 70.3%, 49.9% and 39.7% respectively. The incidence of multiple primary neoplasms was 20.4% .

CONCLUSIONSChinese HNPCC is characterized by early disease onset. Rectal cancer and ascending colon cancer are the first and the secondly common cancer for Chinese HNPCC. Gastric cancer is the most common parenteral cancer in Chinese HNPCC families.

Adult ; Aged ; Asian Continental Ancestry Group ; China ; epidemiology ; Colorectal Neoplasms, Hereditary Nonpolyposis ; epidemiology ; genetics ; pathology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Prognosis ; Survival Rate ; Young Adult

Colorectal cancer is one of the most common malignancies in the world. Many mouse models have been developed to evaluate features of colorectal cancer in humans. These can be grouped into genetically-engineered, chemically-induced, and inoculated models. However, none recapitulates all of the characteristics of human colorectal cancer. It is critical to use a specific mouse model to address a particular research question. Here, we review commonly used mouse models for human colorectal cancer.
Adenomatous Polyposis Coli ; genetics ; pathology ; Animals ; Colorectal Neoplasms ; chemically induced ; etiology ; genetics ; pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; pathology ; Disease Models, Animal ; Genetic Engineering ; Humans ; Inflammation ; complications ; Mice ; Mice, Transgenic ; Neoplasm Metastasis

OBJECTIVETo investigate the therapeutic principles and prognosis of synchronous primary colorectal carcinomas (SCC).

METHODSThe data of 66 SCC patients surgically treated from 1984 to 2003 were retrospectively reviewed.

RESULTSThe synchronous primary colorectal carcinomas were diagnosed and resected simultaneously in 65 patients except one that was misdiagnosed. Thirty patients underwent combined resection, 35 patients segmental resection. Sixty-two patients received radical resection, while three patients had palliative resection due to hepatic metastasis. The overall postoperative 3-, 5-, 10-year survival rates were 70.3%, 60.0%, 40.6%, respectively. In the patients who had simultaneous radical resection, the 3-, 5-, 10-year survival rates were 76.0%, 65.9%, 46.4% respectively.

CONCLUSIONThe extent of resection should be individually determined by the lesion location, extent and distance between the lesions, as well as the patient's general condition. More extensive bowel resection, such as total or subtotal colectomy are suggested for those patients with hereditary nonpolyposis colorectal carcinoma syndrome in order to reduce or avoid the risk of metachronous colorectal carcinoma. The postoperative survival in patients with synchronous primary colorectal carcinoma is similar to those with solitary lesion.

Adult ; Aged ; Colorectal Neoplasms ; mortality ; pathology ; surgery ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; surgery ; Female ; Humans ; Male ; Middle Aged ; Neoplasms, Multiple Primary ; genetics ; surgery ; Ovarian Neoplasms ; surgery ; Prognosis ; Stomach Neoplasms ; surgery ; Survival Rate

OBJECTIVETo set up a sensitive and stable technique which has high throughout to detect the instability of microsatellite DNA.

METHODSGenomic DNA extracted from the cancer tissues and their normal tissues were subjected to microsatellite instability(MSI) analysis on five of DNA markers in 115 sporadic colorectal cancers by means of PCR and ion-pair reversed-phase high performance liquid chromatography. Genomic DNA extracted from lymphocytes in blood of 20 normal persons were analysed and used as the standard control.

RESULTSSeventeen (14.8%) MSI-H and 23(20.0%) MSI-L were found in 115 sporadic colorectal cancers. The rates of MSI in the young patients and old patients were much higher than that in the middle-age patients (P<0.05). And the rate of MSI in low differentiation group was also much higher than that in high or middle differentiation groups (P<0.05).

CONCLUSIONThe method the authors developed is a sensitive and accurate technique to detect MSI and has a high throughput.

Adult ; Chromatography, High Pressure Liquid ; methods ; Colonic Neoplasms ; genetics ; pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; pathology ; DNA, Neoplasm ; analysis ; genetics ; Humans ; Loss of Heterozygosity ; Microsatellite Repeats ; genetics ; Middle Aged ; Rectal Neoplasms ; genetics ; pathology ; Reproducibility of Results ; Sensitivity and Specificity

OBJECTIVETo investigate the incidence of microsatellite instability (MSI) in sporadic colorectal carcinoma (CRC) using BAT-25 and BAT-26 loci, and its association with clinicopathological features.

METHODSMicrosatellite analysis was performed on tissue samples from 73 primary and 53 metastatic tumors collected at the Department of Pathology, Fudan University Cancer Hospital in 2002. Genomic DNA was extracted from paraffin-embedded tissues. Microsatellite alterations of BAT-25 and BAT-26 were detected using fluorescent PCR followed by fragment analysis on automatic DNA sequencer with GeneScan 3.1 software. A case of hereditary nonpolyposis colorectal cancer syndrome (HNPCC) with known high-frequency MSI (MSI-H) was included as positive control.

RESULTSEleven out of 73 samples from primary tumors (15.1%) were MSI-positive and significantly associated with patient age, tumor site, differentiation and prognosis (P < 0.05). There was no significant difference between the positive rate of MSI in tissue samples from primary and metastatic sites among the 53 metastatic tumors, being 17.0% and 13.2%, respectively, P > 0.05. Two cases with negative MSI at the primary site but positive at the metastatic sites were observed.

CONCLUSIONMSI is a frequent molecular event that may serve as a useful parameter for studying tumor biological behavior. MSI plays a partial role in the metastasis of sporadic CRC, but the role of mismatch repair genes and its exact mechanism remains to be determined. The classification of sporadic CRC according to MSI may be of importance both theoretically and practically.

Adenocarcinoma ; genetics ; secondary ; Adult ; Aged ; Colonic Neoplasms ; genetics ; pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; genetics ; secondary ; Male ; Microsatellite Repeats ; Middle Aged ; Prognosis ; Rectal Neoplasms ; genetics ; pathology