Infection with Helicobacter pylori (H. pylori) increases stomach cancer risk. Helicobacter pylori strains with the cag pathogenicity island (PAI) induce more severe inflammation in the gastric epithelium and are more strongly associated with stomach cancer risk than strains lacking the PAI. We examined whether the prevalence of somatic p53 mutation in gastric adenocarcinoma differed between subjects with and without infection with CagA(+) (a marker for the PAI) H. pylori strains. DNA from 105 microdissected tumor specimens was analyzed for mutation in exons 5-8 of the p53 gene by polymerase chain reaction-based single-strand conformation polymorphism followed by direct DNA sequencing. Enzyme-linked immunosorbent assays for IgG antibodies against H. pylori and CagA were performed on sera collected 2-31 years prior to cancer diagnosis. Tumors from CagA(+) subjects were significantly more likely to have p53 mutations than tumors from CagA(-) subjects (including H. pylori- and H. pylori(+)/CagA(-)): odds ratio = 3.72; 95% confidence interval, 1.06-13.07 after adjustment for histologic type and anatomic subsite of tumor and age at diagnosis and sex of subjects. Mutations were predominantly insertions and deletions (43%) as well as transition mutations at CpG dinucleotides (33%). The data suggest that CagA(+) H. pylori infection, when compared with CagA(-) infection or the absence of H. pylori infection, is associated with a higher prevalence of p53 mutation in gastric adenocarcinoma.

IntroductionRandomized trials indicate that adjuvant radiotherapy plus tamoxifen decrease the five-year risk of recurrence among ductal carcinoma in situ patients treated with breast-conserving surgery from about 20% to 8%. The aims of this study were to examine the use and impact of these therapies on risk of recurrence among ductal carcinoma in situ patients diagnosed and treated in the community setting.MethodsWe identified 2,995 patients diagnosed with ductal carcinoma in situ between 1990 and 2001 and treated with breast-conserving surgery at three large health plans. Medical charts were reviewed to confirm diagnosis and treatment and to obtain information on subsequent breast cancers. On a subset of patients, slides from the index ductal carcinoma in situ were reviewed for histopathologic features. Cumulative incidence curves were generated and Cox regression was used to examine changes in five-year risk of recurrence across diagnosis years, with and without adjusting for trends in use of adjuvant therapies.ResultsUse of radiotherapy increased from 25.8% in 1990-1991 to 61.3% in 2000-2001; tamoxifen increased from 2.3% to 34.4%. A total of 245 patients had a local recurrence within five years of their index ductal carcinoma in situ. The five-year risk of any local recurrence decreased from 14.3% (95% confidence interval 9.8 to 18.7) for patients diagnosed in 1990-1991 to 7.7% (95% confidence interval 5.5 to 9.9) for patients diagnosed in 1998-1999; invasive recurrence decreased from 7.0% (95% confidence interval 3.8 to 10.3) to 3.1% (95% confidence interval 1.7 to 4.6). In Cox models, the association between diagnosis year and risk of recurrence was modestly attenuated after accounting for use of adjuvant therapy. Between 1990-1991 and 2000-2001, the proportion of patients with tumors with high nuclear grade decreased from 46% to 32% (P = 0.03) and those with involved surgical margins dropped from 15% to 0% (P = 0.03).ConclusionsThe marked increase in the 1990s in the use of adjuvant therapy for ductal carcinoma in situ patients treated with breast-conserving surgery in the community setting only partially explains the 50% decline in risk of recurrence. Changes in pathology factors have likely also contributed to this decline.

For adequately experienced cytopathologists, ThinPrep is acceptable for FNA of salivary masses, neck cysts, metastatic lymph nodes, and thyroid lesions. Conventional smear technique should be used for FNA of nonmetastatic lymphoid lesions. Use of ThinPrep can complement use of the conventional (smear) cytopreparatory technique when aspirate is nondiagnostic or bloody, when the patient has a blood-borne infectious disease, when the clinician is inexperienced, or when aspirate has entered the syringe.

Flat epithelial atypia is an alteration of mammary terminal duct lobular units that is considered to be a precursor to, or early stage in, the development of some forms of ductal carcinoma in situ. No prior study has systematically evaluated the relationship between various clinico-pathologic features of ductal carcinoma in situ and the presence of coexistent flat epithelial atypia. An understanding of such relationships could provide insight into the connection between flat epithelial atypia and ductal carcinoma in situ. We reviewed slides from 543 ductal carcinoma in situ patients enrolled in a case-control study assessing epidemiologic and pathologic risk factors for local recurrence. We examined the association between the presence of flat epithelial atypia and various clinical factors, pathologic features of the ductal carcinoma in situ, and the presence of coexistent atypical ductal hyperplasia, lobular neoplasia, and non-atypical columnar cell lesions. In univariate analysis, the presence of flat epithelial atypia was significantly related to ductal carcinoma in situ nuclear grade (most common in low grade, least common in high grade; Po0.0001), architectural pattern (most common in micropapillary and cribriform, least common in comedo; Po0.0001), absence of comedo necrosis (Po0.001), absence of stromal desmoplasia (P ¼ 0.02) and absence of stromal inflammation (P ¼ 0.03). In multivariable analysis, features of ductal carcinoma in situ independently associated with flat epithelial atypia were micropapillary and cribriform patterns and absence of comedo necrosis. Additionally, flat epithelial atypia was significantly associated with the presence of atypical ductal hyperplasia, lobular neoplasia, and columnar cell lesions in both univariate and multivariable analyses. These observations provide support for a precursorproduct relationship between flat epithelial atypia and ductal carcinoma in situ lesions that exhibit particular features such as micropapillary and cribriform patterns and absence of comedo necrosis.