Effect of Helicobacter pylori infection on p53 expression of gastric mucosa and adenocarcinoma with microsatellite instability

AIM： To investigate the relationship between Helicobacter pyiori（H pylori） infection, microsatellite instability and the expressions of the p53 in gastritis, intestinal metaplasia and gastric adenocarcinoma and to elucidate the mechanism of gastric carcinogenesis relating to Hpyloriinfection. METHODS： One hundred and eight endoscopic biopsies and gastric adenocarcinoma were available for the study including 33 cases of normal, 45 cases of gastritis, 30 cases of intestinal metaplasia, and 46 cases of gastric adenocardnoma. Peripheral blood samples of these patients were also collected. Hpyloriinfection and p53 expressions were detected by means of streptavidin-peroxidase （SP）immunohistochemical method. Microsatellite loci were studied by PCR-SSCP-CE using the markers BAT-26,D17S261, D3S1283, D2S123, and D3S1611. NSI was defined as the peak shift in the DNA of the gastric tissue compared with that of the peripheral blood samples. Based on the number of mutated MSI markers, specimens were charac-terized as high MSI （MSI-H） if they manifested instability at two or more markers, low MSI （MSI-L） if unstable at only one marker, and microsatellite stable （MSS） if they showed no instability at any marker.RESULTS： H pylori infection was detected in the samples of gastritis, intestinal metaptasia, and gastric adenocarcinoma and the infection frequencies were 84.4%, 76.7%, and 65.2%, respectively, whereas no Hpyloriinfection was detected in the samples of normal control. There was as ignificant difference in the infection rates between gastritis and carcinoma samples （P = 0.035）. No MSI was detected in gasbitis samples, one MSI-H and two MSI-L were detected among the 30 intestinal metaplasia samples, and 12 MSI-H and 3 MSI-L were detected in the 46 gastric carcinomas. In those gastric cardnomas, the MSI-H frequency in Hpylori-positive group was significantly higher than that in Hpylori-negative group. No p53 expression was detected in the normal and gastritis samples from dyspeptic patients. P53-positive immunohistochemical staining was detected in 13.3% of intestinal metaplasia samples and in 43.5% of gastric carcinoma samples. The levels of p53 in Hpylori-positive samples were higher than those in the negative group when the carcinoma samples were subdivided into H pylori-positive and -negative groups （P = 0.013）. Eight samples were detected with positive p53 expression out of the 11 MSI-H carcinomas with Hpyloriinfection and no p53 expression could be seen in the Hpylori-negativesamples.CONCLUSION： H py/ori affect the p53 pattern in gastric mucosa when MMR system fails to work. Mutations of the p53 gene seem to be an early event in gastric carcinogenesis.

Evaluation of spiral CT imaging in the diagnosis of the primary ureteral carcinoma

Objective: To explore the characteristics of the primary ureteral carcinoma (PUC) and discuss the value of spiral CT (SCT) in the diagnosis of PUC. Methods: The SCT findings of the primary ureteral carcinoma in 16 cases were analyzed and compared with the histopathological diagnosis and staging. Results: The transverse diameters of the lesions were 1.0–2.1 cm, and the longitudinal lengths were 1.5–15.2 cm. There were no statistically significant differences (P>0.1) in diam- eters and lengths among the low staging group (pT0–T2) and the high staging group (pT3–T4). The average CT value of the lesions was 43 HU on plain scanning, and 73 HU on CE scanning. The increment was 30 HU. The lesions were clearer on CE scanning. Curved planar reconstruction (CPR) could show the entire course of the urinary tract. Among 6 cases of pT3 stage, CT gave a correct diagnosis in 1 case. For 2 cases of pT4 stage, CT gave correct diagnoses in both cases. Conclusion: The carcinomatous lesions spread along the ureter. The longitudinal length of each lesion is longer than its transverse diameter. Tumor cannot be staged merely according to its diameter and length. CT is difficult to differentiate stage T0–T3, while for stage T4, CT diagnosis is accurate. Contrast enhancement CT scanning has the confirming and differentiating roles. CPR offers direct and easy observing images for clinical doctors.

Mismatch repair gene hMSH2 protein as predictive maker for gastric carcinoma

Objective: To study the possibility of mismatch repair gene hMSH2 as a marker to predict the occurrence of gastric carcinoma. Methods: Immunohistochemical method was used to detect hMSH2 protein expressions of gastric carci- nomas (carcinoma group) and their surrounding epithelia (surrounding epithelium group) in patients and the epithelia (normal epithelium group) in persons without carcinoma. Results: The positive rates of hMSH2 protein expression in nucleus of carcinoma, surrounding epithelium and normal epithelium groups were 44.94% (71/158), 28.48% (45/158) and 11.76% (4/34), respectively (P=0.000); the positive rates of hMSH2 protein expression in plasma of the 3 groups were 37.97% (60/158), 27.85% (44/158) and 23.53% (8/34), respectively (P=0.084); the positive rates of hMSH2 protein expression in both nucleus and plasma of the 3 groups were 20.89% (33/158), 17.72% (28/158) and 2.94% (1/34), respectively (P=0.045). Although the difference of positive rates between carcinoma and surrounding epithelium groups was not significant (P=0.476), both of them were higher than that of normal epithelium group (P=0.018). Conclusion: Our findings show that the detection of hMSH2 protein expression in gastric epithelia may help to predict and diagnose gastric carcinoma.

Characters of normal prostate and prostate cancer lesions by transrectal contrast enhanced ultrasonography

Objective:The aim of the study was to observe the characters and differences of the inner and outer parts of prostate gland, the prostatic cancer lesions in inner and outer parts of prostate glands by transrectal contrast enhanced ultrasonography (TRCEUS) in order to provide valuable information for diagnosing of prostatic cancers. Methods: The ultrasound contrast agent was SonoVue (from Bracco Company, Italian). Instrument adopted Esaote Company Technos DU8 (transrectal ultrasonography). We observed the starting and ending times of transrectal contrast enhancement in the normal prostate inner gland group (16 cases), normal prostate outer gland group (16 cases), and the prostatic cancer lesions in inner gland group (8 cases) as well as in outer gland group (11 cases), respectively. Results: There was no significant difference in the starting time of the normal prostate glands between the inner gland and outer gland groups (P>0.05), likewise no significant difference between the cancer lesions in the inner gland and outer gland groups (P>0.05), but starting times of the cancer lesions in both groups were earlier than those of the normal prostate inner and outer glands groups (P<0.01). The ending time of enhancement was no significant difference among all groups (P>0.05). Conclusion: The earlier starting time of contrast enhancement in prostatic cancer lesions by TRCEUS has important value of distinguishing the cancer lesions from normal prostate glands. It is helpful to diagnose the prostatic cancer lesions.

The Role of Expression of Mismatch Repair Proteins hMSH2 and hMLH1 in Gastric Carcinogenesis and Its Clinical Significance

OBJECTIVE To investigate the expression of the mismatch repair proteins hMSH2 and hMLH1, and to examine the clinical significance of the intracellular expression site （ICES） in gastric carcinogenesis. METHODS Specimens from 172 cases of gastric cancer, 151 tissues from paraneoplastic gastric mucosa and 34 from noncancerous gastric mucosa were collected in Dalain, China. An immunohistochemical method was used to determine the expression of the hMSH2, hMLH1 proteins and their ICES in the gastric mucosas. RESULTS The rate of hMSH2 expression in gastric cancers, paraneoplastic gastric mucosas and noncancerous gastric mucosas were respectively 69.8%, 49.7% and 32.4%. The rate was significantly higher in gastric cancer compared to the latter two groups （P=0.000）, but there was no obvious difference in the expression between the two latter groups （P=0.067）. The hMLH1 protein expression rates were respectively 73.3%, 57.6% and 41.2% in the above three groups. The expression was significantly higher in the gastric cancer group compared to the two latter groups （P=0.000）, while there was no significant difference between the latter groups （P=0.082）. There was no obvious correlation between the hMSH2 and hMLH1 protein expression rates and related factors, such as gender, age and differentiated level of gastric cancer etc. The cell-nuclear expression of the hMSH2 protein was respectively 70.0%, 58.7% and 36.4% in the gastric cancer, paraneoplastic gastric mucosa and noncancerous gastric mucosa groups. The cytoplasmic expression rates were 30.0%, 41.3% and 63.6% in the three groups. The cell-nuclear expression rate of the hMSH2 protein gradually decreased in the gastric mucosas in the following order： cancer, paraneoplastic and noncancerous but cytoplasmic expression only increased slightly in these groups （r=0.161, P=0.020）. There was no significant difference in the ICES of the hMLH1 protein among the three different gastric mucosas （P=0.659）. CONCLUSION Simultaneous determination of the expression and ICES of the mismatch repair proteins hMSH2 and hMLH1 in the gastric mucosa may be helpful in detecting early gastric cancer.

Lymphatic metastasis is related to the epithelialmesenchymal transition and expressions of VEGF, MMP-9, and COX-2 in breast cancer

The invasion and metastasis of breast cancer are supposed to involve several stages in which epithelial-mesenchymal transition(EMT)is regarded as the mechan-istic basis for the behavior of cancer cells.A series of factors related to EMT are apparently involved in such process.The current study aimed to investigate the contributions of EMT and related factors in lymph node metastasis of breast cancer.The expressions of E-cadherin(E-Cad),N-cadherin(N-Cad),vascular endothelial cell growth factor(VEGF),matrix metalloproteinase-9(MMP-9),cyclooxygenase-2(COX-2),and CD34 were examined in 74 cases of breast cancer,including 39 cases with lymph node metastasis and 35 cases without lymph node metastasis by immunohistochemistry.Multivariable Cox proportional hazards model was used to analyze the patients’prognosis.The expressions of N-Cad,VEGF,MMP-9,and COX-2 in cases with lymph node metastasis were significantly higher than those without lymph node metastasis(P<0.05),while the E-Cad level was inversely related to status of lymph node metastasis(P<0.05).The metastasis rate of lymph node in the cases with EMT(lower E-Cad expression and higher N-Cad expression)was 78.3%,while that without EMT(higher E-Cad expression and lower N-Cad expression)was 11.1%.There was a statistical difference in the expression of COX-2 protein between histological grade I and grade II or III,respectively(P<0.05).In the cases with higher grade,the expression of E-Cad was decreased,while that of N-Cad was increased.Higher microvascular density(MVD)was also found to be significantly associated with lymphatic metastasis(P<0.05),and the cases with higher MVD had shorter survival time.This study indicates that EMT and expressions of VEGF,MMP-9 and COX-2,and MVD value are strongly correlated with lymph node metastasis in breast cancer.