BACKGROUND:The most reliable prognostic factor in colon cancer is the TNM classification. The objective of this study was to assess and compare the prognostic role of tumor-infiltrating lymphocytes (TILs) in stage II colon cancer. METHODS: Immunohistochemistry was used to assess the density of TILs that were positive for cluster of differentiation 3 (CD3) (T-cell coreceptor), CD45 isoform RO (CD45RO) (protein tyrosine phosphatase), nuclear transcription factor forkhead box P3 (FOXP3), and CD25 (a type I transmembrane protein) according to tumor site (intraepithelial and stromal) in samples from 87 patients who had stage II colon cancer. These variables were evaluated for their association with histopathologic features along with overall survival (OS) and disease-free survival (DFS). RESULTS: Intraepithelial CD3-posititve (CD3þ), CD45ROþ, CD25þ, and FOXP3þ TILs were associated significantly with better DFS (P ¼ .049, P ¼ .009, P ¼ .013, and P ¼ .001, respectively). The estimated 5-year OS rates for patients who had high-density CD45ROþ and FOXP3þ expression was 100% for both compared with 79.2% and 78.8% for patients who had low-density CD45ROþ and FOXP3þ expression (P ¼ .017 and P ¼ .040, respectively). A significant prognostic factor for both OS and DFS was high-density stromal CD45ROþ lymphocytic infiltration (OS: P ¼ .031; relative risk [RR], 0.134; 95% confidence interval [CI], 0.015-1.164; DFS: P ¼ .013; RR, 0.198; 95% CI, 0.055-0.710); whereas intraepithelial FOXP3þ expression was an independent prognostic factor for DFS (P ¼ .032; RR, 0.108; 95% CI, 0.014-0.821). CONCLUSIONS: FOXP3þ and CD45ROþ TILs demonstrated independent prognostic significance for survival in the current investigation. These results may help to improve the prognostication of early stage colon cancer. Cancer 2010;116:5188-99.

Aggressive natural killer (NK) cell leukemia (ANKL) is a prototype of an Epstein-Barr virus (EBV)-associated lymphoid malignancy, which is characterized by a fulminant clinical course and a median survival interval <2 months. EBV negativity in ANKL is uncommon, and the characteristics of EBV-negative ANKL are not well defined. We compared the clinicopathological characteristics of EBV-negative ANKL patients (group 1, n = 2) with those of EBV-positive ANKL patients (group 2, n = 14) and reviewed the literature for reports on EBV-negative ANKL cases. EBV-negative and EBV-positive ANKL patients had similar clinical and pathological characteristics, but EBV-negative patients had a longer survival than EBV-positive patients (11.5 vs. 1.5 months, respectively). EBV-negative patients achieved complete remission, but tumors often relapsed after a short interval. In conclusion, EBV-negative ANKL is an uncommon malignancy that pursues a less aggressive clinical course than EBV-positive ANKL.

Hydroa vacciniforme-like lymphoma and extranodal-type natural killer (NK)/T-cell lymphoma are prototypes of Epstein-Barr virus (EBV)-associated cutaneous T- or NK-cell lymphomas. Hydroa vacciniforme-like lymphoma with systemic spread and extranodal-type NK/T-cell lymphoma are characterized by aggressive clinical course. We describe 2 patients with primary cutaneous EBV-associated T-cell lymphomas who did not satisfy the criteria for well-defined entities and showed unusual, prolonged clinical course. They presented with skin ulcerations and mass lesions confined to the extremities without systemic involvement. Skin biopsies demonstrated dense superficial and deep perivascular and periappendageal lymphoid infiltrates expressing CD3 and CD8, but not CD56. The EBV genomes were found within the tumor cells, and monoclonal T-cell receptor gene rearrangement was present. We suggest that these cases represent a peculiar subtype of EBV+ cutaneous T-cell lymphoma, with a tendency to localize in the skin of the extremities and has an indolent clinical course.

Background: Products of cyclin-dependent kinase inhibitor p16^INK4Aand mitotic arrest defective protein 2 (MAD2) genesare key regulator proteins at the G1 restriction point and mitotic checkpoint of the cell cycle. The objective of this study was to investigate the role of promoter methylation of p16^INK4A and MAD2 genes in gastric marginal-zone B-cell lymphoma (MZBCL). Materials and Methods: Gastric biopsies from 40 patients were analyzed by methylation-specific polymerase chain reaction, and the methylation status was compared with the results of BCL10 expression and t(11;18)(q21;q21) translocation. Results and Conclusion:p16^INK4A was methylated in 30 of 40 MZBCLs (75%). The lymphomas with p16^INK4A methylation tended to be negative for t(11;18)(q21;q21) (p = 0.011). MAD2 gene was methylated in 23 of 38 MZBCLs (61%). Lymphomas with MAD2 gene methylation more frequently expressed BCL10 (p = 0.037). These methylation profiles suggest that p16^INK4A and MAD2 gene may play a role in the pathogenesis of MZBCL via different pathways; MAD2 gene is Helicobacter pylori independent with a close association with BCL10 while p16^INK4A is H. pylori dependent with an inverse correlation with the t(11;18)(q21;q21) translocation.

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