Kyung Ryoul Kim

Expression of DBC1 and SIRT1 is associated with poor prognosis for breast carcinoma.

Recently, it has been reported that SIRT1 and DBC1 may be involved in the development of tumors and predict poor survival in some cancers. However, their exact role is not clear. Therefore, we investigated the expression status and clinical significance of DBC1 and SIRT1 expression in breast carcinomas. We evaluated the immunohistochemical expression of DBC1, SIRT1, and p53 using a 3-mm core from 122 patients with breast cancer for tissue microarray. Positive expression of DBC1 and SIRT1 were seen in 71% and 67% of patients, respectively. In the patients with breast cancer, overall, expression of DBC1 and SIRT1 was significantly associated with distant metastatic relapse and shorter relapse-free survival and overall survival by univariate analysis. Tumor stage and DBC1 and SIRT1 expression were also independent prognostic factors by multivariate analysis. Among the patients who had received chemotherapy, DBC1 and SIRT1 expression was significantly associated with distant metastatic relapse and shorter survival by univariate analysis. DBC1 expression was also associated with distant metastatic relapse and shorter survival in patients who had received endocrine therapy, according to univariate and multivariate analysis. In conclusion, this study shows that expression of DBC1 and SIRT1 is a significant prognostic indicator for breast carcinoma patients.

SIRT1 Expression is Associated With Poor Prognosis of Diffuse Large B-Cell Lymphoma

Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. Recently, it is suggested that SIRT1 may be involved in the development of malignant tumors including mouse lymphoma. Therefore, we investigated the prevalence and the prognostic impact of SIRT1 expression in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical expression of SIRT1, p53, bcl2, CD10, bcl6, and multiple myeloma-1 (MUM1) were evaluated by using a 2 mm core from 104 DLBCL patients for tissue microarray. Positive expression of SIRT1 was seen in 74% (77/104) of patients. In total DLBCL patients, SIRT1 and p53 expression were significantly associated with shorter overall survival (OS) by univariate analysis (P=0.001 and P=0.011, respectively). SIRT1 was also an independent prognostic factor by multivariate analysis (P=0.01). According to the expression patterns of CD10, bcl6, and MUM1, germinal center B cell (GCB) types were represented in 38 cases (37%) and non-GCB types were represented in 66 cases (63%). In the GCB type, only p53 expression was associated with a significantly shorter OS (P=0.032). In the non-GCB type, expression of SIRT1 correlated with shorter OS by univariate analyses (P=0.005) and multivariate analyses (P=0.049). In conclusion, we showed that SIRT1 expression is a clinically significant prognostic indicator for DLBCL patients.

Expression and prognostic significance of SIRT1 in ovarian epithelial tumours.

Aims: Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide‐dependent deacetylase. Recently, some studies have suggested that SIRT1 could be over‐expressed in breast, prostate and colon cancers and up‐regulated SIRT1 inactivates p53 by deacetylation. Therefore, we investigated the prevalence and the prognostic impact of SIRT1 and p53 expression in ovarian epithelial tumours. Methods: Immunohistochemical expression of SIRT1 and p53 were evaluated using tissue microarray in 40 cases of benign epithelial tumours, 36 cases of borderline tumours, and 90 cases of malignant tumours. Results: Expression of SIRT1 was significantly increased in malignant epithelial tumours compared to benign and borderline epithelial tumours (p < 0.001). In particular, a high proportion of serous carcinoma expressed SIRT1 (86%, 55/64 cases). Despite the frequent expression of SIRT1 in malignant ovarian epithelial tumours, serous carcinomas of high FIGO stage showed less frequent SIRT1 expression compared to that of low stage serous carcinomas (p = 0.029). Moreover, increased expression of SIRT1 in serous carcinoma correlated with increased overall survival by univariate (p = 0.014) and multivariate analyses. Conclusions: Over‐expression of SIRT1 may play an important role in the early stage of ovarian carcinogenesis.

The role of serum response factor in hepatocellular carcinoma: an association with matrix metalloproteinase.

Serum response factor (SRF) regulates tran-scription of immediate early genes and triggers proliferation, migration and differentiation in several types of cells. Matrix metalloproteinases (MMPs), a group of zinc-dependent endopeptidases, play a crucial role in tumor invasion and metastasis. However, expression of SRF and its association with MMPs in hepatocellular carcinoma (HCC) have not been elucidated. We examined the expression levels of SRF, MMP-2 and MMP-9 in HCC tissues using Western blot assay. We also examined the effect of SRF on MMP expression and enzyme activity in HCC by transfection of SRF cDNA in HLE cells. Protein expression of SRF, MMP-2 and MMP-9 showed a significant increase in HCC tissues, compared with those of corresponding non-tumor tissues. High SRF expressing HCC tissues showed higher levels of expression of MMP-2 and MMP-9, compared with low SRF expressing HCC tissues. In addition, overexpression of SRF in HLE cells led to increased levels of expression of mRNA and protein, as well as increased enzyme activity of MMP-2 and MMP-9. Overexpression of SRF also led to significantly enhanced migration of HLE cells. These results suggest that overexpression of SRF in HCC may play an important role in tumor cell migration and invasion through upregulation of MMP-2 and MMP-9.

Co-expression of cox-2, C-met and beta-catenin in cells forming invasive front of gallbladder cancer.

PURPOSE Gallbladder cancer is a malignancy with poor prognosis, predominantly resulting from invasion and metastasis. Our previous studies have demonstrated that prostaglandin E(2) (PGE(2)), generated by cyclooxygenase 2 (Cox-2), transactivates epidermal growth factor receptor (EGFR), c-Met and beta-catenin; thus, enhancing colon cancer cell growth and invasiveness in vitro. To determine whether these findings are applicable to clinical conditions, we examined the expression and cellular localization/co-localization of Cox-2, c-Met, beta-catenin, EGFR and c-erbB2 in gallbladder cancer. MATERIALS AND METHODS Thirty-five specimens of invasive gallbladder cancer, 8 in situ carcinoma and 7 adenoma specimens were immunostained with specific antibodies against Cox-2, c-Met, beta-catenin, EGFR and c-erbB2. The cellular distribution, localization and colocalization were examined, and the signal intensities quantified in: a) the central area of gallbladder cancer and b) cancer cells forming the invasive front. RESULTS Cox-2, c-Met, beta-catenin, c-erbB2 and EGFR were over-expressed in 80, 74, 71, 62 and 11% of invasive gallbladder cancers, respectively. beta-catenin was expressed in 80% of non-malignant specimens, exclusively in the cell membrane, while the cancer specimens showed cytoplasmic and/or nuclear staining. Significantly higher Cox-2, c-Met and beta-catenin expressions were present in cancer cells of the invasive front than in the tumor central areas (p<0.001), and these expressions were significantly (p=0.01) associated with the invasion depth. Co-expressions of Cox-2, c-Met, beta-catenin and c-erbB2 were present in 42% of the specimens in cancer cells forming the invasive front. CONCLUSION The overexpressions, and often co-localizations, of Cox-2, c-Met and beta-catenin in cancer cells forming the invasive front indicate their local interactions and important roles in invasion.

Concurrent large cell neuroendocrine carcinoma and adenocarcinoma of the ascending colon: a case report.

Large cell neuroendocrine carcinomas of the colon are rare and represent only a small percentage of all colonic endocrine tumors. Here, we report a case of a colonic large cell neuroendocrine carcinomas concurrent with a colonic adenocarcinoma. A 70-year-old man presented with acute abdominal pain. A spiral computed tomography scan of the abdomen revealed eccentric wall thickening on the ascending colon. An explorative laparotomy and a right hemicolectomy were performed. Grossly, two separated masses were observed in the proximal ascending colon. One was a 7.4 × 5.1 cm ulcerative fungating lesion, and the other was a 2.8 × 1.9 cm polypoid lesion. Microscopically, the ulcerative fungating lesion showed a well-differentiated neuroendocrine morphology with necrosis and increased mitosis. Most of the tumor cells had large, vesicular nuclei with eosinophilic nucleoli, variable amounts of eosinophilic cytoplasm, and immunoreactivity for chromogranin A and synaptophysin. The polypoid lesion was a well-differentiated adenocarcinoma that had invaded the submucosa. We diagnosed these lesions as a concurrent large cell neuroendocrine carcinoma and an adenocarcinoma of the ascending colon.