Objective To refine the loss of heterozygosity (LOH) on chromosome 7q21－22 and identify the new tumor suppressor gene(s) in colorectal tumorigenesis. Methods Fifteen polymorphic microsatellite markers were analyzed on chromosome 7 and another 5 markers were applied on chromosome 7q21-22 region in 83 cases of colorectal cancer and normal DNA by PCR. PCR products were electrophoresed on an ABI Prism 377 DNA sequencer. GeneScan 3.1 and Genotyper 2.1 software were used for LOH scanning and analysis. Results A distinct region of frequent allelic deletion was observed on chromosome, another 5 polymorphic microsatellite markers were applied to 7q21-22 and the minimal region of frequent LOH was established on 7q21-22 spanning the D7S657, D7S646 locus. Conclusion Through detailed deletion mapping studies, a critical and precise region spanning the D7S657, D7S646 locus is identified, which must contain one or more unknown tumor suppressor gene(s) on colorectal cancer.
ObjectiveTo detect the expression of hMLH1, hMSH2 or hMSH6 protein in sporadic colorectal carcinoma (SCRC) and analyze the relationship of its expression to clinicopathologic parameters of patients with SCRC. MethodsTwo hundred and sixty-three patients with SCRC were studied, who underwent surgery in the Department of General Surgery, the Air Force General Hospital; and the Department of Colorectal Surgery, Beijing Cancer Hospital from March 2008 to March 2012. All the patients were diagnosed by histological examination without chemoradiotherapy before operation. Immunohistochemistry was used to detect the hMLH1, hMSH2 or hMSH6 protein expression in the tumor tissues from 263 cases of SCRC. The relationship of its expression to clinicopathologic parameters was analyzed. ResultsThe loss rates of hMLH1, hMSH2, and hMSH6 expressions in the tumor tissues from 263 patients with SCRC were 13.3% (35/263), 12.2% (32/263), and 28.9% (76/263), respectively. The loss rates of hMLH1/hMSH2, hMLH1/ hMSH6, hMSH2/hMSH6, and hMLH1/hMSH2/hMSH6 expressions were 3.4% (9/263), 10.2% (27/263), 6.8% (18/263), and 3.4% (9/263) corresponding. The loss rate of hMLH1 expression in the high differentiated adenocarcinoma tissues was significantly higher than that of the moderate to low differentiated adenocarcinoma or mucous carcinomas tissues (P < 0.01). The loss rate of hMLH2 expression in the tissues of tumor size more than 5 cm was significantly higher than that in the tissues of tumor size less than 5 cm (P < 0.05). The loss rate of hMSH6 expression in the male patient was significantly higher than that of the female patient (P < 0.01) and which in the tumor tissues of less lymph node metastasis was significantly higher than that in the tissues of the more lymph node metastasis (P < 0.01). ConclusionsThe hMLH1, hMSH2, or hMSH6 gene expression deletion is common in SCRC and the relation with the clinical pathology of SCRC is obviously different from Lynch syndrome. Therefore, the effects of hMLH1, hMSH2, and hMSH6 expressions on the development, invasion, and metastasis of SCRC are different from Lynch syndrome too.
Objective To construct and verify a genetically engineered mouse model which is similar to clinical sporadic colorectal cancer and simultaneously expresses KrasLSL-G12D/- and Smad4loxp/loxp genes. Methods The Krastm4Tyj/J mouse and Smad4tm2.1Cxd/J mouse were transformed into the genetic background, and the genotypes of the offspring mice were identified by the PCR to obtain the mice expressed simultaneously KrasLSL-G12D/- and Smad4loxp/loxp genes. The LentivirusCre-IRES-Luciferase was injected into the submucosa of the model mice and the tumorigenicity was observed under the IVIS system. The tumor tissues of the model mice were sampled and the HE staining was used to verify the tumorigenicity of the model mice. Results The genetically engineered mouse model which could simultaneously express KrasLSL-G12D/- and Smad4loxp/loxp genes was obtained by the breeding and selection. The mouse intestinal epithelial cell carcinogenesis was successfully induced by the viral vector containing Cre recombinase. Conclusion Mouse model expressed simultaneously KrasLSL-G12D/- and Smad4loxp/loxp genes is capable of sporadic tumorigenicity by Cre recombinase and could simulate pathological process of human sporadic colorectal cancer.
ObjectiveTo analyze expressions of interleukin-6 (IL-6) and microsatellite instability (MSI) in ulcerative colitis-associated colorectal cancer (UC-CRC) and investigate role of IL-6 and MSI in carcinogenesis of patients with UC.MethodsThe postoperative pathological data of patients with UC-CRC and patients with sporadic colorectal cancer (SCRC) admitted by Edong Healthcare Group from January 2013 to January 2019 were analyzed retrospectively. The expressions of MMR proteins, including hMLH1, hPMS2, hMSH2, and hMSH6, were detected by the immunohistochemical method. The serum IL-6 levels of the patients with UC, UC-CRC, SCRC and control patients (non-UC, non-UC-CRC, non-SCRC) were detected. The correlation between the IL-6 and MMR protein expression in the cancer tissue was analyzed.ResultsThere were 43 patients with UC, 17 UC-CRC, 55 SCRC, and 30 control patients. The total rate of MMR-deficient (dMMR) was 41.2% (7/17) in the patients with UC-CRC. There were significant correlations between the hMLH1 and hPMS2 protein expression deletion and between the hMSH2 and hMSH6 protein expression deletion (P<0.001). The serum level of IL-6 in the patients with UC-CRC was significantly higher than that in the patients with UC (t=4.97, P<0.001) and the patients with SCRC (t=5.26, P=0.006). The dMMR might be associated with the level of IL-6 in the patients with UC-CRC, which wasn’t associated with it in the patients with SCRC (rs=0.04, P=0.77).ConclusionsSimilar to SCRC, MSI also plays a role in occurrence and development of UC-CRC. dMMR in patient with UC-CRC is more common in co-expression deficiency of hMLH1 and hPMS2, as did hMSH2 and hMSH6. IL-6 is not involved in mechanism of MSI-related canceration of colorectal cancer, but it is speculated that IL-6 might be involved in occurrence of MSI of UC-CRC.
ObjectiveTo investigate the relationship between family history of malignant tumor (FHOMT) and clinicopathological features of patients with sporadic papillary thyroid carcinoma (PTC), and to provide basis for individualized diagnosis and treatment.MethodsPatients admitted to the department of breast and thyroid surgery in Renmin Hospital of Wuhan University from January 1, 2017 to September 30, 2019 for thyroid surgery for the first time and pathologically diagnosed as PTC were collected. According to the presence or absence of FHOMT, tumor type and family member type, their clinicopathological features were compared.ResultsIn 2 123 patients, there were 1 932 patients without FHOMT and 191 patients with FHOMT. The most common FHOMT was the family history of lung cancer (1.80%). Compared with PTC patients without FHOMT, PTC patients with FHOMT had a later onset age (P=0.000), a lower proportion of central lymph node metastasis (P=0.004), and a lower ratio of capsule invasion (P=0.021). PTC patients with respiratory-related FHOMT had a later onset age (P=0.000). PTC patients with male first-degree relatives had a later onset age (P=0.000). And PTC patients whose first-degree relatives were female had a lower proportion of central lymph node metastasis (P=0.007).ConclusionThere are differences in onset age, central lymph node metastasis and capsule invasion between PTC patients with and without FHOMT.
Stroke with hereditary cerebral small vessel diseases is a rare disease. Its clinical manifestations include early-onset ischemic lacunar or hemorrhagic stroke with high disability. Its typical imaging markers include lacunes, white matter hyperintensities, microbleeds, intracerebral hemorrhages located in deep or lobe of brain, crotical microinfarcts, and enlarged perivascular spaces. As the clinical and neuroimaging signs and symptoms of hereditary cerebral small vessel diseases often overlap with sporadic cerebral small vessel diseases, it is hard to diagnose. This article summarizes the clinical features, importance of obtaining valuable family history, genetic diagnosis, and management of stroke with hereditary cerebral small vessel disease to improve its accuracy diagnosis.