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Hypermethylation in the promoter region of the p16 gene was suspected to be involved in the tumorigenesis of colorectal cancers, although its clinical and biological significance remains obscure. In this study, we collected 84 T3N0M0 stage primary colorectal cancers that were curatively resected. The clinicopathologic data were reviewed. p16 hypermethylation was determined by a methylation-specific polymerase chain reaction (PCR). p53 overexpression was detected by immunocytochemistry (ICC). The point mutations in the 12 and 13 codons of the K-ras gene were screened by restriction enzyme analysis. Loss of heterozygosity (LOH) of the DCC (Deleted in Colorectal cancer) gene was examined by PCR using primers of the DCC (18q21) microsatellite marker. The DNA replication error (RER) was examined using 7 microsatellite markers at distinct chromosomal loci. p16 hypermethylation, regarded as an indication of p16 inactivation, was evident in 24 (28.6%) of the tumors. No correlation was found between p16 hypermethylation and various clinicopathologic factors, includinig age, sex, tumor location, tumor size, growth pattern, tumor differentiation, mucin production, vascular and/or lymphatic invasion, lymphocyte infiltration of the tumor, and serum level of carcinoembryonic antigen. There was no association between p16 hypermethylation of K-ras gene mutation, p53 overexpression and LOH of the DCC gene. However, p16 hypermethylation was significantly associated with DNA RER (p = 0.01). Survival analysis revealed a significant survival disadvantage of p16-hypermethylated versus non-p16-hypermethylated tumors (p = 0.0001). These findings indicate that p16 hypermethylation plays a role in the carcinogenesis of a subset of colorectal cancers; and the presence of p16 hypermethylation predicts shorter survival in T3N0M0 stage colorectal cancers.

ObjectiveTo evaluate the association of clinicopathologic factors and prognostic value with the expression of cyclooxygenase 1 and 2 in patients with gastric adenocarcinoma. Summary Background DataEpidemiologic studies have indicated that nonsteroidal antiinflammatory drugs reduce the risk of colon cancer by as much as 40% and also decrease the risk of gastric cancer. Recently, gastric cancer was found to express constitutive cyclooxygenase 1 and inducible cyclooxygenase 2 isoenzymes. Nonsteroidal antiinflammatories, which may function as cyclooxygenase inhibitors, inhibited the growth of gastric cancer cells. These two isoenzymes' expressions associated with traditional clinicopathologic factors have not been fully evaluated, and their prognostic value for determining survival in patients remains to be clarified. MethodsSeventy-one specimens resected from patients with gastric adenocarcinoma were investigated by immunohistochemical stain against cyclooxygenase 1 and 2. The 71 specimens were divided into stain-positive and stain-negative groups. Correlations between cyclooxygenase 1 and 2 expression, various clinicopathologic factors *including vascular invasion and Helicobacter pylori infection), and prognosis were studied. ResultsThe cyclooxygenase 2-positive group was significantly correlated with vascular invasion and H. pylori infection by univariate and multivariate analysis. In patients with cyclooxygenase 2-positive cancer, the prognosis was significantly poorer than in those with cyclooxygenase 2-negative cancer. However, multivariate analysis showed that vascular invasion, serosal invasion, and lymph node metastasis were independent prognostic factors for patients with gastric cancer, but cyclooxygenase 2 expression was not. There was no significant correlation between cyclooxygenase 1 expression and clinicopathologic factors and prognosis. ConclusionsUpregulated cyclooxygenase 2 expression was associated with H. pylori infection in gastric cancer and was also strongly correlated with positive vascular invasion, which was an independent prognostic factor for poorer survival in this study. The usefulness of cyclooxygenase 2 inhibitors in the prevention or treatment of gastric cancer remains undetermined but deserves further investigation.Gastric cancer is a major cause of death throughout the world 1 and is the fourth most common malignancy in Taiwanese men and the sixth in women.2 Gastric cancer recurred in 39% of patients who had undergone curative resection, 3 and many chemotherapeutic drugs have failed to provide complete reduction of gastric cancer in the patients. 4 Recent epidemiologic studies have shown that chronic intake of nonsteroidal antiinflammatory drugs (NSAIDs), which function as cyclooxygenase inhibitors, reduced the incidence of colon cancer and polyps by as much as 40% to 50%. 5,6 In a large prospective study, the use of aspirin was also associated with a reduced risk of gastric and esophageal cancer. 7,8

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Purpose Breast cancer is increasing around the globe, including Asia. We aimed to examine the survival and risk of contralateral breast cancer (CBC) in Asian breast cancer patients with BRCA mutations. MethodsA total of 128 breast cancer patients with germline BRCA mutations and 4,754 control breast cancer patients were enrolled. Data on clinical pathologic characteristics, survival and CBC were collected from the medical record. The rates of survival and CBC were estimated by Kaplan-Meier method. Results The mean age of onset in BRCA mutation carriers was significantly younger than control patients (BRCA vs. Non-BRCA: 43.9 vs. 53.2 years-old). BRCA mutation carriers had a higher proportion of triple-negative breast cancer (TNBC) (52%) than control patients (12%, p<0.001). The risk of CBC was significantly higher in BRCA mutation patients than in control cases (hazard ratio (HR) = 3.95, 95% CI 2.71-5.75); when stratified by genotype, the HRs (95%CI) were 4.84 (3.00-7.82) for BRCA1 and 3.13 (1.78-5.49) for BRCA2 carriers, respectively. Moreover, BRCA1 mutation patients with triple-negative breast cancer (TNBC) as their first breast cancer had the highest risk of CBC (HR = 5.55, 95% CI 3.29-9.34). However, we did not observe any differences in relapse-free survival and overall survival between mutation carriers and control patients. ConclusionOur study suggest that BRCA patients had a significantly higher risk of developing CBC, particularly for BRCA1 mutation carriers with TNBC as the first breast cancer.