Eric Caspers

Early-onset gastric carcinomas display molecular characteristics distinct from gastric carcinomas occurring at a later age.

Gastric cancer is thought to result from a combination of environmental factors and accumulation of specific genetic alterations, and consequently mainly affects older patients (>50 years of age). Fewer than 10% of patients present with the disease before 45 years of age and these young patients are thought to develop carcinomas with a different molecular genetic profile from that of sporadic carcinomas occurring at a later age. Forty early‐onset gastric carcinoma resection specimens were characterized for microsatellite instability (MSI) and loss of heterozygosity status using 22 polymorphic microsatellite markers. Twenty‐four biopsies were additionally evaluated for the presence of MSI. No MSI was observed in any of the cases analysed. Losses were infrequent, but were most common for the D1S234 (26.1%) and D1S1676 (17.4%) markers, flanking the RUNX3 gene; for the p53ALU (23.1%) and TP53 (15.4%) markers, near the TP53 gene; and for the D16S2624 (17.2%) marker, near the E‐cadherin (CDH1) gene. All cases with loss of CDH1, as well as 6/7 cases with loss of TP53, displayed aberrant staining of the corresponding proteins, pointing to a functional role for these proteins in early‐onset gastric carcinogenesis. No germline CDH1, TP53 or RUNX3 mutations were detected in any of the cases analysed. No correlation was observed between non‐functional E‐cadherin and the histological type of the tumours analysed. Finally, Epstein–Barr virus was not detected in any of the cases analysed. On the basis of these results, early‐onset gastric carcinomas appear to have characteristics distinct from gastric carcinomas occurring at a later age. Copyright

Immunohistochemical and Genetic Analysis of Non- Small Cell and Small Cell Gallbladder Carcinoma and Their Precursor Lesions

Gallbladder carcinomas can be highly lethal neoplasms. Relatively little is known about the genetic abnormalities that underlie these tumors, particularly with respect to their timing in neoplastic progression. The authors evaluated 5 noninvasive dysplasias and 33 invasive gallbladder carcinomas (6 small cell carcinomas, 27 non–small cell carcinomas, of which 16 were accompanied by an in situ carcinoma component) for expression of the protein products of the p16, p53, Dpc4, and pRB tumor suppressor genes by immunohistochemistry. Neoplasms were also evaluated for the presence of activating K-ras oncogene mutations. Seventy-five percent of non–small cell gallbladder carcinomas demonstrated loss of p16 expression, whereas 63% accumulated high levels of p53. Loss of Dpc4 and pRB expression was less frequent, seen in 19% and 4% of the neoplasms, respectively. Thirty percent of neoplasms harbored activating K-ras mutations. In contrast, 100% of the small cell carcinomas of the gallbladder demonstrated inactivation of the pRB/p16 pathway; 67% showed loss of pRB expression, and the other 33% lost p16 expression. Eighty-three percent of small cell carcinomas accumulated high levels of p53, whereas loss of Dpc4 expression and activating K-ras mutations were not found. Among 15 evaluable in situ components, 13 harbored the same alterations found in the invasive component. Inactivation of p16 and p53 occur in the majority of non–small cell gallbladder carcinomas. Dpc4 inactivation and K-ras mutations occur in a significant minority of cases. pRB loss is uncommon in non–small cell gallbladder carcinoma, but virtually all small cell carcinomas inactivate the p16/pRB pathway, usually by retinoblastoma protein loss. It is noteworthy that all of these alterations occur at the level of carcinoma in situ.

Diagnostic p53 Immunostaining of Endobiliary brush cytology : Preoperative cytology compared with the surgical specimen

Endobiliary brush cytology is important in the distinction of malignant and benign causes of extrahepatic bile duct obstruction. The additional diagnostic value of p53 immunostaining on these cytology specimens was assessed.

The prevalence of K-ras mutations in ductal brush cytology and bile of subjects without pancreatic disease using the epidemiologic necropsy as study design

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