These findings suggest that hSgo1-downregulated colorectal cancers have a clinicopathological character of CIN, and hSgo1 downregulation leads to CIN in colorectal cancer cells.

No abstract

Gastric cancer has striking heterogeneity in histological pattern, cellular phenotype, genotype, biomarkers, and biological behavior. We focused on the specific morphological papillary phenotype of gastric adenocarcinoma and attempted to identify its distinct molecular characteristics. In our comparative study, early stage papillary (papillary-dominant) gastric cancer showed a significantly higher and more widespread high-frequency microsatellite instability (MSI-H) than other morphological types. Analysis of mutations in a panel of five putative microsatellite instability (MSI)-associated genes in the MSI-H cases revealed that papillary or papillary-dominant cancer displays a unique profile of mutations compared to profiles previously reported in gastric cancer. Immunohistochemical staining and methylation analysis revealed that silencing of hMLH1 by methylation in its promoter region was responsible for the failure of mismatch repair in papillary-type gastric cancer, whereas aberrant promoter methylation of hMLH1 was not found in any cases without the unique mutator phenotype. Promoter hypermethylation of the hMLH1 genes was found to a lesser degree in the adjacent non-tumor mucosa in four of the 10 cases with tumor having the mutator phenotype. Microsatellite instability itself could not be detected in the adjacent non-tumor mucosa. Inactivation of hMLH1 expression by promoter hypermethylation may be an early event in carcinogenesis of this type of gastric cancer, preceding the development of the clear MSI phenotype of papillary carcinoma.

The effects of treatment in a hydrated autoclave (121 °C, 2 atm for 20 min), microwave oven (in water), and simple heating (60 °C overnight in distilled water or 90 °C for 10 min in ZnSO4) on the stainability of 56 antigens by commercially available antibodies in formalin‐fixed paraffin‐embedded tissue sections were evaluated. The detectability of nuclear antigens, glycoprotein, lymphocytic surface markers, and chromogranin A was significantly and reproducibly improved by these treatments, whereas the detectability of viral antigens and peptide hormones was attenuated or unchanged. This enhancement includes not only the distinctiveness of the positive staining, but also the number of positive cells, as revealed by comparing serial sections. Among these four heating procedures, microwave heating and autoclaving were more effective than the others on p53, c‐erbB‐2, and CA125, whereas simple heating was best for smooth‐muscle actin (HHF35 and CGA7). Generally the effects of the heating procedures for these antigens were consistent among the cases, but the effects on GFAP varied with the case. The alterations we observed could significantly influence the interpretation of immunohistochemical staining of currently popular tumor markers such as p53 in terms of their prevalence (28%vs 64% in gastric cancer; 36%vs 82% in metastatic liver cancer) and other diagnostically important markers.

SUMMARY:Chromosomal or centromerical numerical abnormality (CNA) is a well-known characteristic of human cancer, but the extensive and specific documentation of CNA in gastric cancer is still sparse, partly because of difficulty in obtaining cytogenetic information. Taking advantage of a recently developed fluorescence in situ hybridization protocol for formalin-fixed paraffin-embedded tissues, we investigated CNA of 51 gastric cancer cases with a panel of 18 chromosome-specific ␣-satellite probes (for chromosomes 1-4, 6 -12, 15-18, 20, X and Y) and region specific probes (c-myc and p53) to enumerate respective chromosome numbers in interphase nuclei. The involved chromosomes exhibiting CNA were nonrandom in gastric cancer. Aberrations of chromosomes 1, 8, 17, 20, and X were frequent regardless of histologic types, whereas aberrations chromosomes 10, 15, and 18 occurred less often (p Ͻ 0.001). From a histopathologic standpoint, the mucocellular type had stable CNA in comparison with the tubular type (mucocellular type vs tubular type carcinoma: 21.0 Ϯ 10.63% vs 62.8 Ϯ 12.79%, p Ͻ 0.001). Interestingly, there was less extensive CNA in women (men vs women: 54.3 Ϯ 9.49% versus 24.9 Ϯ 12.23%, p Ͻ 0.001). A dramatic difference in the outcome was detected according to the involvement of chromosomes 3, 10, 11, 12, 17, and Y; that is, the cases with CNA of these chromosomes had worse prognosis. (Lab Invest 2003, 83:1311-1320.

A 53-year-old woman presented with symptoms of weight loss, diarrhea, and melena. A barium enema with endoscopy revealed multiple colonic polyps which were shown histologically to be metastatic deposits of poorly differentiated adenocarcinoma. The primary tumor, a poorly differentiated gastric adenocarcinoma, had been resected 11 years earlier. This appears to be only the second published report of polypoid colonic metastases from gastric adenocarcinoma.

Practicing pathologists expect major somatic genetic changes in cancers, because the morphological deviations in the cancers they diagnose are so great that the somatic genetic changes to direct these phenotypes of tumors are supposed to be correspondingly tremendous. Several lines of evidence, especially lines generated by high-throughput genomic sequencing and genome-wide analyses of cancer DNAs are verifying their preoccupations. This article reviews a comprehensive morphological approach to pathology archives that consists of fluorescence in situ hybridization with bacterial artificial chromosome (BAC) probes and screening with tissue microarrays to detect structural changes in chromosomes (copy number alterations and rearrangements) in specimens of human solid tumors. The potential of this approach in the attempt to provide individually tailored medical practice, especially in terms of cancer therapy, is discussed.

Gastrointestinal tract tumours are notorious for their diYculty in relation to conventional cytogenetic analysis. In particular, necrosis, the presence of stromal inflammatory and other cells, and poor attachment of tumour cells have led to problems with the quality and reliability of cytogenetic preparations, even with the recently developed fluorescence in situ hybridisation (FISH) technique. Furthermore, background autofluorescence masks the weak hybridisation signals in the nuclei. To overcome this problem, brief microwave treatment was applied for the identification of centromeres by in situ hybridisation in gastric cancer cells. Using this technique, a panel of 17 centromeric specific -satellite probes was used to detect chromosomal instability in these cells. Lymphocyte controls and cancer cells subjected to irradiation achieved the hybridisation threshold in 30 minutes, providing a significant diVerence when compared with the nonirradiated samples (mean (SD) frequency of diploid cells 97% (2.1%) v 76% (4.6%), respectively). Therefore, this protocol of intermittent microwave treatment is recommended as a simple, rapid, and highly reproducible technique for application to various types of probe. It also gives well defined hybridisation signals and reduces background "noise". (J Clin Pathol: Mol Pathol 1999;52:357-359)