The presence of AMAs and autoreactive T and B cells, in conjunction with the co-occurrence of other autoimmune diseases, characterizes PBC as a typical autoimmune disease. 3 Although the etiology of PBC remains obscure,
Aim: To investigate the pathobiological features of intestinal and diffuse-type gastric carcinomas in the Japanese population. Methods: The expression of fragile histine triad (FHIT), phosphatase and tensin homology deleted from human chromosome 10 (PTEN), caspase-3, Ki-67, mutant p53, matrix metalloproteinase (MMP)-2, MMP-9, and extracellular matrix metalloproteinase inducer (EMMPRIN) on tissue microarrays of gastric carcinomas by immunostaining was examined in comparison with the clinicopathological characteristics between intestinal and diffuse-type cases. Results: Intestinal-type carcinoma frequently occurred in old men, whereas the diffuse type comparatively occurred more in young women (p,0.05). The diffuse-type carcinoma was more inclined to invasion into muscularis propria, lymphatic invasion and lymph node metastasis, and belonged to higher International Union against Cancer (UICC) staging (p,0.05) compared with intestinal-type counterparts. Expression of FHIT, PTEN, Ki-67, caspase-3, mutant p53 and EMPPRIN was higher in intestinal-type carcinomas than in diffuse-type carcinomas (p,0.05). Kaplan-Meier analysis indicated that patients with intestinal-type carcinomas had a higher cumulative survival rate (p,0.05). Conclusion: Intestinal-type gastric carcinomas with a more favourable prognosis frequently show high levels of proliferation and apoptosis, and always accompany strong expression of FHIT, PTEN and mutant p53 and EMMPRIN. EMMPRIN expression might underlie the molecular basis of liver metastasis and higher proliferation of intestinal-type gastric carcinomas in Japan. Lauren's classification thus proved pathologically relevant for the clinical treatment of gastric carcinomas.
Immunostaining depending on antigen-antibody specificity is the commonest approach for determining the localization of specific antigens in tissue sections. This procedure is applicable not only with frozen or specially fixed samples, but also has proved reliable with formalin-fixed paraffin-embedded tissue sections through improvement of antigen-retrieval. Immunostaining is thus firmly established as a tool for diagnostic pathology and in our institute multiple antibodies are applied for 13-15% of the cases examined, as well as H&E staining. With the standard approach, approximately 3 h is necessary from the beginning of deparaffinization till covering sections with the Envision system. We utilized intermittent microwave irradiation for 10 min during hybridization with primary and secondary antibodies in a special moist-chamber, to achieve all immunostaining steps within 1 h in 178 primary antibodies frequently used for diagnostic pathology. According to our 5 years experience, such microwave irradiation not only obtained significant specific staining for enhancing the specificity of antigen-antibody reactions, but also inhibited nonspecific binding. We present herein the details of the methodology and recommendations for its application with particular primary antibodies. This method can contribute to savings in time and energy, allowing pathologists to rapidly obtain diagnostic information.
CXCL16 is a new member of the chemokine superfamily, which exists in a transmembrane as well as a soluble form. Its receptor CXCR6 is detected on CD4 + T cells, CD8 + T cells, and natural killer T cells. Here, we report a significant correlation of CXCL16 expression by tumor cells with the infiltration of T cells and prognosis in colorectal cancer (CRC). We first found that CXCL16 expression was consistently up-regulated more in tumor tissues than in normal mucosa derived from the same CRC patients. Four human CRC cell lines also expressed CXCL16 mRNA and secreted soluble CXCL16. We next examined the expression of CXCL16 and infiltration of lymphocytes in CRC specimens (n = 58) by immunohistochemistry. CRC patients with high levels of CXCL16 expression (n = 43) had higher levels of CD4 + and CD8 + tumor-infiltrating lymphocytes (TIL; P < 0.01) than those with low levels of CXCL16 expression (n = 15). Furthermore, the high CXCL16 expression group showed significantly better prognosis than the low CXCL16 expression group (P < 0.05). Collectively, our data suggest that the expression of CXCL16 by tumor cells enhances the recruitment of TILs, thereby bringing about a better prognosis in CRC. Thus, CXCL16 is a new prognostic biomarker and may be useful for the development of a more effective therapeutic strategy for CRC. [Cancer Res 2007;67(10):4725-31]
The receptor for advanced glycation end products (RAGE) is a cell surface multiligand receptor of the immunoglobulin superfamily, which participates in physiological and pathological processes such as neuronal development, diabetes, inflammation, neurodegenerative disorders, and cancer. A novel splice variant of RAGE-endogenous secretory decoy form (esRAGE) was recently identified and is thought to be a prospective candidate to modify these RAGE-associated conditions. Here, we investigated the expression and distribution of esRAGE and RAGE proteins with domain-specific antibodies. We studied a wide variety of adult normal human preparations obtained from surgical and autopsy specimens using a tissue microarray technique. The results revealed that esRAGE was widely distributed and we classified its expression into four patterns. In pattern A, the cytoplasm is stained diffusely in neurons, vascular endothelium, pneumocytes, mesothelium, pancreatic b cells, and macrophages/monocytes. In pattern B, dot-like granules are stained in the supranuclear regions facing the luminal surface of the bile ducts, salivary glands, digestive tracts, renal tubules, prostate, skin, thyroid, and bronchioles. Pattern C is represented by diffuse staining in the stromal area of the arterial walls. Pattern D shows diffuse and strong staining of secreted materials such as thyroidal colloid, crystals in renal tubular lumen, and glandular lumen in prostate. This study provides, for the first time, a histopathological basis for understanding the physiological roles of esRAGE in humans, and will contribute to elucidating the participation of esRAGE in pathological processes and to exploring novel diagnostic and therapeutic concepts.
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