Tumor budding is useful for prognosis and identifying patients with Stage II colon cancer who have a high risk of disease recurrence after curative surgery.

G1 cyclins and cyclin-dependent kinase (CDK) complexes play important roles in G1 cell cycle transition, and their overexpression is implicated for neoplasia. The p27 protein (p27) negatively regulates G1progression by binding to G1 cyclins/CDK complexes and inhibits their activity, resulting in inhibition of entry to the cell cycle. We investigated overexpression of cyclin D1 (CCND1), cyclin D2 (CCND2), cyclin E (CCNE), CDK2, and CDK4, in addition to p27, in 260 gastric cancer cases on the basis of Western blots, reverse transcriptase-polymerase chain reaction Southern blots, and immunohistochemistry to clarify the roles of these proteins in tumor progression and prognosis. Examination of 20 cases of fresh cancer and matched normal tissues demonstrated a clear tendency for increased mRNA synthesis to be more frequent than expected from protein levels, and a direct correlation between p27 protein and mRNA was not found. Immunohistochemistry demonstrated 21.5%, 34.2%, 30.4%, 44.2%, and 48.0% positivity for CCND1, CCND2, CCNE, CDK2, and CDK4, respectively, in the 260 gastric cancer cases. Overexpression of CCND2 and CDK4 significantly correlated with tumor progression. Moreover, CCND2 cytoplasmic staining (26.2%) appeared to be strictly linked with progression, whereas nuclear staining (7.8%) demonstrated an inverse correlation. Survival curves showed CCND2 (especially cytoplasmic staining) and CDK4 positivity to be associated with a poor prognosis and CCNE positivity with a better prognosis. Tumors with high p27 labeling indices (LIs) were well differentiated, with low levels of invasion and lymph node metastasis. p27-negative cases (37.3%) demonstrated a poor prognosis. Multivariate analysis revealed positivity for CCND2 and negativity for p27 to be independent prognostic factors. There were no direct links among CCND2, CCNE, CDK4, and p27. The Cell cycle transitions are regulated by a series of G1 cyclins (cyclin Ds and E) and cyclin-dependent kinase (CDK) complexes. The cyclin Ds (CCNDs)-CDK4 and cyclin E (CCNE)-CDK2 complexes are catalytically active during late G1 and are linked to regulation of G1/S progression in mammalian cells.

Tumour budding is a practical and significant histological index for identification of high malignant potential and poor outcome in patients with colorectal carcinoma.

No abstract

No abstract

Clinicopathologic features of GAED differ from those of CGA. GAED shows aggressive biological behavior, and is characteristically immunoreactive to AFP, glypican 3, or SALL4.

No abstract

This study evaluated whether the increased risk of development of gastric carcinoma due to chronic Helicobacter pylori infection could be linked with elevated cell proliferative activity and expression of p53 and bcl-2. Forty-eight patients undergoing therapy for H pylori-positive gastroduodenal ulcers were separated into not eradicated (NE; n = 23) and eradicated (E; n = 25) groups 6 months after the treatment. Serum pepsinogen (PG) 1:11 ratios and histologic changes in the gastric corpus and the antrum, assessed according to the modified Sydney System, as well as epithelial cell proliferation (mitosis, Ki67, and proliferating cell nuclear antigen [PCNA]), and expression of oncoproteins (p53 and bcl-2) were examined before and at 3 months and 6 months after treatment for H pylori. Manuscript received October 10, 1996; revision accepted January 3,1997.A d d r e s s r e p r i n t requests to Dr Mitomi: D e p a r t m e n t of Pathology, Kitasato University East Hospital, Asamizodai 2-1-1, Sagamihara, 228 Japan. infection was associated with a low PG 1:11 ratio, increased inflammation and activity score, and elevated cell proliferation, as evidenced by the Ki67 and PCNA labeling indexes and the mitotic index in the NE group. Scattered accumulation of p53 protein continued to be observed in the NE group after treatment but was significantly decreased in the E group. We conclude that persistent H pylori infection causes gastritis, with epithelial degeneration and regeneration that result in accentuation of epithelial cell proliferation and accumulation of p53 protein, presumably heightening the genetic instability consistent with the development of carcinoma. (Key words: Helicobacter pylori; Gastritis; Cell proliferation; Ki67; p53; Gastric carcinoma) Am J Clin Pathol 1997;108:26-34. degeneration and regeneration of the mucosal epithelium that could facilitate malignant transformation. To test that hypothesis, H pylori-positive patients received treatments aimed at eradication and were then divided into groups depending on whether eradication was successful. Determinations of the serum pepsinogen (PG) 1:11 ratio, as a parameter for inflammation, and anti-H pylori antibody titer were made, along with estimates of cellular proliferation and expression of p53 and bcl-2 proteins in the mucosa, for comparison between patients in whom H pylori was eradicated and those in whom it was not. PATIENTS AND METHODS PatientsForty-eight patients with H pylori infection were studied, including 31 with gastric ulcers, 13 with duodenal ulcers, and 4 with gastroduodenal ulcers. The regimens for eradication therapy were selected by a double-blind method. From the results of the rapid urease test and histologic detection of H pylori, 26