Survival analysis of local excision vs total mesorectal excision for middle and low rectal cancer in pT1/pT2 stage and intermediate pathological risk.

BACKGROUND: Local excision (LE) is a feasible treatment approach for rectal cancers in stage pT1 and presents low pathological risk, whereas total mesorectal excision (TME) is a reasonable treatment for more advanced cancers. On the basis of the pathology findings, surgeons may suggest TME for patients receiving LE. This study compared the survival outcomes between LE with/without chemoradiation and TME in mid and low rectal cancer patients in stage pT1/pT2, with highly selective intermediate pathological risk. METHODS: This retrospective study included 134 patients who received TME and 39 patients who underwent LE for the treatment of intermediate risk (pT1 with poor differentiation, lymphovascular invasion, perineural invasion, relatively large tumor, or small-sized pT2 tumor) rectal cancer between 1998 and 2016. RESULTS: Overall survival (OS), disease-free survival (DFS), and cumulative recurrence rate (CRR) were similar between the LE (3-year DFS 92%) and TME (3-year DFS 91%) groups. Following subgrouping into an LE with adjuvant therapy group and a TME without adjuvant therapy group, the compared survival outcomes (OS, DFS, and CRR) were found not to be statistically different. The temporary and permanent ostomy rates were higher in the TME group than in the LE group (p < 0.001). Rates of early and late morbidity following surgery were higher in the TME group (p = 0.005), and LE had similar survival compared with TME. CONCLUSION: For patients who had mid and low rectal cancer in stage pT1/pT2 and intermediate pathological risk, LE with chemoradiation presents an alternative treatment option for selected patients.

Primary tumor location in stage III colon cancer has prognostic impact on subsequent liver metastasis.

BACKGROUND AND OBJECTIVES: We aim to investigate whether a difference exists between right-sided and left-sided colon cancer at the same disease stage and subsequent liver metastasis and identify whether tumor location can independently influence survival. METHODS: Right-sided colon cancer was defined as malignancy arising from the cecum to the transverse colon; left-sided colon cancer was defined as malignancy arising from the splenic flexure to the sigmoid colon. Clinicopathological features and survival data were collected for analysis. RESULTS: Overall, 1442 patients were included for analysis. The median follow-up time was 58.2 months. Patients with left-sided colon cancer had better 5-year overall survival (75.2% vs 61.7%, P = 0.005), 5-year cancer-specific survival (81.6% vs 73.4%, P = 0.001), and 5-year recurrence-free survival (70.9% vs 66.5%, P = 0.033) compared with patients having right-sided colon cancer. After the presentation of subsequent liver metastasis, patients with primary left-sided colon cancer had better 3-year cancer-specific survival ( P < 0.001). In the multivariate analysis, cancer location was an independent prognostic factor for cancer-specific survival (right vs left, HR: 1.276, 95% CI: 1.002-1.625). CONCLUSIONS: The primary tumor location can serve as a prognostic factor for treatment outcomes either in primary stage III colon cancer or subsequent liver metastasis.

Various clinicopathological features of patients with metachronous colorectal cancer in relation to different diagnostic intervals.

BACKGROUNDS: Clinicopathologic factors relating to developing metachronous colorectal cancer (CRC) have been reported. However, the effects of different diagnostic intervals on these risk factors required further analysis. PATIENTS AND METHODS: This retrospective study comprised 14,481 patients diagnosed from January 1995 to December 2012. Metachronous CRC was defined as the occurrence of a second colorectal cancer at least 1 year post-operatively. RESULTS: A total of 153 (1.06%) patients developed metachronous CRCs during the follow-up. Significantly higher rates of developing metachronous cancer occurred in male patients (1.2 vs 0.9%), patients with synchronous CRC (2.0 vs 1.0%), and patients with a positive family history of CRC (1.4 vs 0.9%). Pertaining to diagnostic intervals related to clinicopathological features, more severe staging was significant in the diagnostic interval between 2 and 3 years (35 vs 7.7%, 20.6%, 17.5%, P = .01) compared with other intervals. Male patients were more frequently detected to have CRC within 3 years compared with females (53.1 vs 29.1%, P = .005). For a diagnostic interval ≧ 5 years, a significantly higher rate of metachronous CRC located at the right colon was observed than that located at the left colon (36.6 vs 19.7%, p = 0.03). CONCLUSIONS: We evinced that a diagnostic interval between 2 and 3 years was a key time for metachronous CRC diagnosis with worse staging distribution. Based on current findings, we recommend the stratification of metachronous CRCs into diagnostic intervals of 1-2, 2-3, and ≧ 3 years, as they exhibit significantly different characteristics.

Overexpression of Lgr5 correlates with resistance to 5-FU-based chemotherapy in colorectal cancer.

BACKGROUND: The leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is an adult intestinal stem cell marker frequently detected in human colorectal cancers (CRCs). However, the value of Lgr5 level in CRC prognosis and treatment prediction has not been well characterized. METHODS: We examined Lgr5 expression in 384 formalin-fixed paraffin-embedded CRC specimens from 296 CRC patients, including 64 patients treated with 5-fluorouracil (5-FU)-based chemotherapy. The effects of Lgr5 on cell proliferation, survival, and drug resistance were examined in cultured CRC cells. RESULTS: Elevated expression of Lgr5 was observed in CRC tissues, and Lgr5 protein levels were significantly correlated with an advanced American Joint Committee on Cancer stage (P < 0.001), T stage (P < 0.001), N stage (P < 0.001), and distant metastasis (P < 0.001). High expression levels of Lgr5 were significantly associated with shorter disease-free survival (P < 0.001) and shorter cancer-specific survival (P = 0.007) in CRC patients. Among the chemotherapy-treated subgroups, patients with low Lgr5 level showed a better response rate (65 %) than patients with high Lgr5 level (37 %) towards 5-FU-based treatment (P = 0.025). In cultured CRC cell lines, knocking down Lgr5 suppressed cell proliferation and colony formation ability, while it enhanced apoptosis and rendered cells more sensitive to chemotherapeutic agents. In contrast, overexpression of Lgr5 increased cell proliferation and enhanced chemoresistance. CONCLUSION: These results suggest that elevated Lgr5 level is associated with CRC progression and treatment response and has the potential to serve as a therapeutic target in CRC patients.

Cellular changes in hepatocytes and intestinal endothelium after hepatoduodenal ligament occlusion and protective effects of caspase inhibition.

INTRODUCTION: Hepatic vascular control is used by many surgeons to prevent massive hemorrhage during hepatectomy. However, this may carry a risk of ischemic damage to the hepatocytes. Another major drawback of intraoperative occlusion of the hepatoduodenal ligament is portal stasis with resultant intestinal congestion which may cause adverse effects on the intestinal functions. CD44 is a transmembrane glycoprotein present in many types of epithelial cells. By mediating the attachment of dividing crypt cells to the basal lamina via hyaluronan, CD44 is considered to play a role in maintaining the intestinal villus integrity. Apoptosis is a pathway of cell death orchestrated by a family of proteases called caspases. ZVAD-fmk is a cell-permeable irreversible inhibitor of caspase and might block the processing of many caspases. This study is designed with the purpose to evaluate the impact of intraoperative occlusion of the hepatoduodenal ligament on hepatocyte and intestine functions and also to evaluate the potential influence of ZVAD-fmk on the hepatocyte and intestine functions. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomized to 5 groups. Group 1(C) underwent sham operation. Group 2 (HDL30) underwent occluding the hepatoduodenal ligament by for 30 minutes. Group 3 (HDL 15) underwent occluding the hepatoduodenal ligament by for 15 minutes, releasing for 5 minutes, underwent occlusion for another 15 minutes. Group 4 (ZHDL30) first received ZVAD-fmk, then underwent occluding the hepatoduodenal ligament by for 30 minutes. Group 5 (ZHDL15) first received ZVAD-fmk, then underwent occluding the hepatoduodenal ligament for 15 minutes, releasing for 5 minutes, underwent occlusion for another 15 minutes. After removing the temporary occlusion, liver tissue and proximal jejunum were harvested. Hepatocyte and intestine apoptosis were quantitated using the TUNEL method. CD 44 status of jejunum were determined by immunohistochemical staining. RESULTS: Hepatocyte apoptosis was significantly increased in group (HDL30) and group (HDL15) when compared with group (C). ZVAD-fmk effectively attenuated this phenomenon in both groups. There was no significant difference between group (HDL30) and group (HDL15). Jejunal apoptosis was significantly increased in group (HDL30) and group (HDL15) when compared with group (C). ZVAD-fmk effectively attenuated this phenomenon in both groups. There was no significant difference between group (HDL30) and group (HDL15). CD44 expression on jejunum was significantly increased in group (HDL30) and group (HDL15) when compared with group (C). ZVAD-fmk failed to effectively diminish this phenomenon. CONCLUSION: Occlusion of the hepatoduodenal ligament significantly increased both hepatocyte and jejunal apoptosis and pretreatment with ZVAD-fmk could effectively diminish such phenomenon. CD44 expression on jejunum was also significantly increased by intraoperative occlusion of the hepatoduodenal ligament, yet pretreatment with ZVAD-fmk failed to show significant effect on such phenomenon.

The -174 G/C polymorphism in interleukin-6 (IL-6) promoter region is associated with serum IL-6 and carcinoembryonic antigen levels in patients with colorectal cancers in Taiwan.

INTRODUCTION: We investigated the associations between -174 G/C polymorphism of interleukin-6 (IL-6) gene promoter and serum IL-6 and carcinoembryonic antigen (CEA) levels in Taiwanese patients with colorectal cancer (CRC). RESULTS AND DISCUSSION: The frequency of the G allele was only 0.043, which is significantly lower compared to Western analogs. On grouping genotypes as G-positive (GG and CG) and G-negative (GG), the average IL-6 level and CEA levels were significantly lower in G-positive patients than in G-negative analogs (IL-6, 3.56 +/- 4.38 vs. 15.38 +/- 9.52 pg/ml, P = 0.021; CEA, 27.7 +/- 25.7 vs. 157.7 +/- 59.6 ng/ml, P = 0.012). The patients without the G allele had higher incidences of synchronous cancers of other origins (P = 0.003). CONCLUSION: In conclusion, ethnicity affects the status of -174 G/C IL-6 polymorphism. This polymorphism status consequently influences the expressions of serum IL-6 and CEA and incidences of synchronous cancers of other origins.

Analysis of the effect of serum interleukin-6 (IL-6) and soluble IL-6 receptor levels on survival of patients with colorectal cancer.

OBJECTIVE: The correlations of serum interleukin-6 and soluble interleukin-6 receptor concentrations with clinicopathological features and survival of patients with colorectal cancer were studied. METHODS: We measured the serum levels of interleukin-6 and soluble interleukin-6 receptor in 99 colorectal cancer patients at the Chang Gung Memorial Hospital, Taiwan. The interleukin-6 and soluble interleukin-6 receptor levels were tested for their association with each other, and with the clinical parameters and outcomes. RESULTS: Both interleukin-6 and soluble interleukin-6 receptor concentrations were significantly higher in colorectal cancer patients than in normal individuals. Unlike patients with serum interleukin-6 levels >10 pg/ml, who have increased carcinoembryonic antigen levels and shorter survival, serum soluble interleukin-6 receptor levels >800 pg/ml were found in patients with stages I-II and no regional lymph nodal invasion and appeared to be a positive prognostic factor for improved survival. Especially, patients with serum interleukin-6 <10 pg/ml and soluble interleukin-6 receptor >800 pg/ml lived significantly longer. Nonetheless, the multivariate analysis showed that only tumor-node metastasis stage, metastatic status and serum interleukin-6 level were independent prognostic factors, whereas the serum soluble interleukin-6 receptor level became marginally important for survival. CONCLUSIONS: We suggest the clinical relevance of interleukin-6 and soluble interleukin-6 receptor for the survival of colorectal cancer patients. From a practical point of view, detection of the serum interleukin-6 level alone, rather than combined measurement of interleukin-6 and soluble interleukin-6 receptor, may be sufficient to independently predict survival in colorectal cancer patients.

Antithrombin-III attenuates hepatocyte apoptosis in bile duct ligated rat: a striking cellular change.

BACKGROUND AND PURPOSE: Retention and accumulation of toxic hydrophobic bile salts within hepatocyte may cause hepatocyte toxicity by inducing apoptosis. This study was designed with the purpose of evaluating the possible effect of antithrombin-III on hepatocyte apoptosis in bile duct ligated rat. MATERIALS AND METHODS: The rats were randomized to 3 groups: group 1 (control, C) underwent sham operation; group 2 (obstructive jaundice, OB) underwent common bile duct ligation; and group 3 (obstructive jaundice with antithrombin-III, OBAT-III) underwent common bile duct ligation and simultaneously were treated with antithrombin-III. Liver tissues were harvested on the fifth postoperative day. RESULTS: Hepatocyte apoptosis was significantly increased in bile duct ligated group when compared with the sham operation group. The administration of antithrombin-III effectively attenuates such phenomenon in obstructive jaundice with antithrombin-III group. CONCLUSION: Bile duct ligation significantly increased hepatocyte apoptosis and the administration of antithrombin-III effectively attenuates such phenomenon.

Macrophage-derived interleukin-6 up-regulates MUC1, but down-regulates MUC2 expression in the human colon cancer HT-29 cell line.

Little is known regarding the effects of IL-6 released by tumor-infiltrating macrophages on the mucin expression of colon cancer cells. We isolated macrophages from healthy donors and harvested the supernatant after 48-h cultures. Using flow cytometry and intracellular staining methods, we found that macrophage supernatant effectively induced MUC1 up-regulation and MUC2 down-regulation of colon cancer cells in vitro. Western blotting analysis using monoclonal antibody against IL-6 or gp 130 verified that this IL-6-driven activity was through the activation of tyrosine phosphorylation (Tyr(705)) of STAT3 in cancer cells. We analyzed the surgical specimens of 29 patients with colon cancer by an immunohistochemical staining method and demonstrated the co-localization of macrophages, and the expression of IL-6, CD68, and MUC1 in colon cancer patients. Therefore, macrophage-derived IL-6 modulates the mucin expression of colorectal cancer cells that might in turn produce a permissive milieu favorable to cancer spread.

Insulin-like growth factor-binding protein-3 in breast cancer: analysis with tissue microarray.

BACKGROUND: IGFBP-3 has been reported to be growth-stimulatory. The creation of tissue microarray (TMA) allows for the rapid immunohistochemical analysis of thousands of tissue samples in a parallel fashion. This study was designed with the application of TMA to analyze the IGFBP-3 status in breast cancer with the hope to elucidate the possible relationship between IGFBP-3 expression and breast cancer biology. MATERIALS AND METHODS: Archival tissue specimens from 97 patients with primary invasive breast cancer were selected. The IGFBP-3 expression was analyzed by TMA. The data of primary tumor staging, age, estrogen receptor status, lymph node status, histological grading and TNM staging were also collected. RESULTS: There were 40 patients (41%) with 0-1 expression of IGFBP-3, 52 patients (54%) with 2 expression of IGFBP-3 and 5 patients (5%) with 3 expression in IGFBP-3. By multivariate analysis, the IGFBP-3 expression turned out to be significantly related to the overall five-year survival rate. CONCLUSION: The preliminary results about IGFBP-3 expression in breast cancer are intriguing and require further evaluation.

Prognostic value of signal transducers and activators of transcription 3 in breast cancer.

INTRODUCTION: Constitutively activated signal transducers and activators of transcription (STAT) proteins are found in various types of tumors. However, there is still very limited information about the role of STATs in breast cancer. The power of tissue microarray technique is the capability of doing a series of analyses of thousands specimens in a parallel fashion with minimal damage to the origin blocks. This study was designed with the application of tissue microarray to analyze the STAT3 status in breast cancer. MATERIALS AND METHODS: Archival tissue specimens from 102 patients with primary invasive breast cancer were selected, and STAT3 expression was analyzed by immunohistochemical staining with tissue microarray. The data of primary tumor staging, age, estrogen receptor status, lymph node status, histologic grading, and tumor-node-metastasis staging were also collected. RESULTS: By multivariate analysis, the STAT3 expression turned out to be significantly related to the overall 5-year survival rate (P = 0.024). CONCLUSION: Immunohistochemical staining with tissue microarray was convenient and feasible for the analysis of STAT3 expression status in breast cancer. Our preliminary results are promising and deserve further evaluation.

Lack of prognostic value of insulin-like growth factor-1 in patients with breast cancer: analysis with tissue microarray.

BACKGROUND: Recent reports on the risk of prostate, breast, colorectal and lung cancer suggested that high circulating insulin-like growth factor-1 (IGF-1) concentrations are associated with an increased risk of cancer. The power of the tissue microarray (TMA) technique is the ability to perform a series of analyses of thousands of specimens in a parallel fashion with minimal damage to the original blocks. MATERIALS AND METHODS: Archival tissue specimens from 106 patients with primary invasive breast cancer were selected and IGF-1 expression was analyzed by immunohistochemical staining of tissue microarrays. The data regarding primary tumor staging, age, estrogen receptor status, lymph node status, histological grading and TNM staging were also collected. RESULTS: There were 2 patients (2%) with grade 1 expression for IGF-1, 39 patients (37%) with grade 2 expression and 65 patients (61%) with grade 3 expression. There was no significant relationship between IGF-1 expression and age (p=0.256), estrogen receptor status (p=0.921), histological grading (p=0.815), primary tumor staging (p=0.455), or TNM staging (p=0.194). No survival difference was noted among the three groups with different IGF-1 expression (p=0.462). CONCLUSION: Immunohistochemical staining of the tissue microarray was convenient and feasible for the analysis of IGF-1 expression in breast cancer, yet its expression did not show any significant correlation with the overall survival rate.

Signal transducer and activator of transcription 1 in breast cancer: analysis with tissue microarray.

BACKGROUND: Constitutively activated signal transducer and activator of transcription (STAT) proteins are found in various types of tumors. However, there is still very limited information about the role of STATs in breast cancer. The power of the tissue microarray analysis (TMA) technique is the capability of performing a series of analyses of thousands of specimens in a parallel fashion with minimal damage to the original blocks. This study was designed to use TMA in determing the STAT1 status in breast cancer tissues. MATERIALS AND METHODS: Archival tissue specimens from 102 patients with primary invasive breast cancer were selected and STAT1 expression was analyzed using immunohistochemical staining with tissue microarray. The data of primary tumor staging, age, estrogen receptor status, lymph node status, histological grading and TNM staging were also collected. RESULTS: There were 18 patients (17.6%) with 0 expression in STAT1, 29 patients (28.4%) with 1 expression in STAT1, 21 patients (20.6%) with 2 expression in STAT1 and 34 patients (33.4%) with 3 expression in STAT1. There was no significant relationship between STAT1 expression and age (p = 0.203), estrogen receptor status (p = 0.221), histological grading (p = 0.861), primary tumor staging (p = 0.918), lymph node status (p = 0.53), or TNM staging (p = 0.826). There was no survival difference noted among the four groups with different STAT1 expression (p = 0.859). CONCLUSION: Immuno-histochemical staining with tissue microarray analysis was convenient and feasible for the analysis of STAT1 expression status in breast cancer. STAT1 expression did not show significant correlation with the overall survival rate.

The kinetic expression of lipopolysaccharide-binding protein and CD14 gene in obstructive jaundice.

BACKGROUND: Binding lipopolysaccharide (LPS) with high-affinity, lipopolysaccharide-binding protein (LBP) and CD14 lower the threshold stimulatory concentrations of LPS dramatically and enhance the rate of cytokine production markedly. This study aimed to investigate the kinetic expression of LBP/CD14 and its possible relationship with tumor necrosis factor alpha (TNF-α) to better understand the pathophysiology of obstructive jaundice. MATERIALS AND METHODS: The tissues (liver, spleen, intestine, and lung) of male Sprague-Dawley rats were harvested at pre-bile duct ligation in controls and at specific time points (24, 48, 72, 96, and 120 hr) after bile duct ligation. LBP, CD14, and TNF-α mRNA expression were measured in tissues harvested from controls and at the specific time points. RESULTS: Hepatic LBP mRNA expression increased significantly at five days after bile duct ligation. CD 14 mRNA expression increased significantly after five days of bile duct ligation in liver, lung, spleen, and ileum. TNF-α mRNA expression increased significantly in all four organs (liver, lung, spleen, and ileum) after four days of bile duct ligation. CONCLUSION: Five days of bile duct ligation upregulated CD 14 mRNA expression in liver, lung, spleen, and ileum and increased TNF-α mRNA expression simultaneously in the liver, lung, spleen, and ileum. In addition, five days of bile duct ligation also upregulated LBP mRNA expression in the liver and increased hepatic TNF-α mRNA expression simultaneously. The kinetic expressions of LBP and CD 14 in obstructive jaundice are intriguing and further evaluation is warranted.

An evaluation of fatty acid-CoA ligase 4 in breast cancer.

BACKGROUND: Fatty acid-CoA ligase 4 (FACL4) has been detected in various types of tumors. However, there is still very limited information about the role of FACL4 in breast cancer. Tissue microarray (TMA) technique analyzes thousands of specimens in a parallel fashion with minimal damage to the original blocks. This study was designed with the application of TMA to analyze the FACL4 status in breast cancer. MATERIALS AND METHODS: Archival tissue specimens from 102 patients with primary invasive breast cancer were selected and FACL4 expression was analyzed by immunhistochemical staining with TMA. The data of primary tumor staging, age, estrogen receptor status, lymph node status, histological grading and TNM staging were also collected. RESULTS: As shown my multivariate analysis, TNM stage was significantly related to the overall five-year survival rate. Nevertheless, FACL4 expression failed to have any significant relationship to overall five-year survival. CONCLUSION: Immuno-histochemical staining with TMA was convenient and feasible for the analysis of FACL4 expression status in breast cancer. Our preliminary results showed that FACL4 expression had no significant prognostic value in breast cancer.

An evaluation of focal adhesion kinase in breast cancer by tissue microarrays.

BACKGROUND: Many studies have shown that focal adhesion kinase (FAK) is a positive regulator of tumor progression and invasion. However, there is still very limited information about the role of FAK in breast cancer. Tissue microarrays (TMA) can analyze thousands of tissue samples in a parallel fashion with minimal damage to the origin block. This study was designed with the application of TMA to analyze the FAK status in breast cancer. PATIENTS AND METHODS: Archival tissue specimens from 98 patients with primary invasive breast cancer were selected and FAK expression was analyzed by immunohistochemical staining with TMA. The data of primary tumor staging, age, estrogen receptor status, lymph node status, histological grading and TNM staging were also collected. RESULTS: There were four patients (4.0%) with grade 1 expression in FAK, 41 patients (41.8%) with grade 2 expression in FAK and 53 patients (54.2%) with grade 3 expression in FAK. There was no significant relationship between FAK expression and age, estrogen receptor status, histological grading, primary tumor staging, lymph node status and TNM stage. By multivariate analysis, the TNM stage was found to be significantly related to the overall five-year survival rate (p<0.00001). CONCLUSION: Immunohistochemical staining with TMA is a convenient and feasible method. Unfortunately, our preliminary results fail to show meaningful prognostic value of FAK in breast cancer. A larger prospective study is warranted for further evaluation.

Yes-associated protein is not an independent prognostic marker in breast cancer.

BACKGROUND: The development of tissue microarray (TMA) technology has provided the opportunity to perform analyses of tissue samples on a large scale in an uniform fashion. This study was designed with the use of TMA to explore the Yes-associated protein (YAP) status in breast cancer. PATIENTS AND METHODS: YAP expression in tumor and tumor-free samples from 94 patients with primary breast cancer was analyzed by TMA. The clinicopathological data for age, estrogen receptor status, histological grading and TNM staging were also collected. RESULTS: There were 29 patients (30.8%) with 1(+) expression, in YAP, 59 patients (62.8%) with 2(+) expression and 6 (6.4%) with 3(+) expression. There was no significant relationship between YAP expression and the other clinicopathological variables. By multivariate analysis, YAP expression failed to produce any significant relationship with the overall survival rate. CONCLUSION: YAP expression is not an independent prognostic factor in patients with breast cancer.

Identification of secretory gelsolin as a plasma biomarker associated with distant organ metastasis of colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide. More than half of all CRC patients will develop metastases, which represents the major cause of death for CRC patients. CRC metastases confined in other organs are potentially resectable, and patients who receive curative resections appear to have better outcomes. Thus, the early detection of metastasis in CRC patients could improve their survival rate after curative surgery. Here, we report the use of Cy-dye labeling combined with multi-dimensional fractionation and mass spectrometry as a proteomics-based approach for identifying CRC metastasis-associated biomarker(s) in plasma samples collected from three CRC patients upon diagnosis of their primary and metastatic tumors. Among the eight identified proteins, we used Western blot analysis and an in-house-developed ELISA to validate the increased plasma levels of one, secretory (plasma) gelsolin, in >80% of CRC patients with distal metastases in a larger sample cohort (32 patients). We also found a significant increase of secretory gelsolin in plasma samples of stage IV versus stages I-III CRC patients before treatment. Furthermore, immunohistochemistry showed that secretory gelsolin was highly overexpressed in CRC tissue specimens compared to adjacent normal tissues, and a cell model study showed that secretory gelsolin may help regulate CRC cell migration.

Cortactin in breast cancer: analysis with tissue microarray.

BACKGROUND: Tissue microarray (TMA) allows the rapid immunohistochemical analysis of thousands of tissue samples in a parallel fashion. This study was designed to analyze the cortactin status in breast cancer using TMA and to investigate the relationship of cortactin status to breast cancer biology. PATIENTS AND METHODS: Archival tissue specimens from 99 patients with primary invasive breast cancer were selected. The cortactin expression was analyzed by TMA. Age, estrogen receptor status, histological grading and TNM staging data were also collected. RESULTS: There were 23 patients (23.2%) with low (+) expression of cortactin, 60 patients (60.6%) with intermediate (++) expression and 16(16.2%) with strong (+++) expression. There was no significant relationship between cortactin expression and age, histological grading, primary tumor staging, lymph node status, estrogen receptor and TNM stage. By multivariate analysis, estrogen receptor status and TNM staging were found to be significantly related to the overall five-year survival rate. CONCLUSION: Cortactin expression failed to demonstrate a prognostic value for patients with breast cancer.

An evaluation of prognostic value of death-associated protein kinase 1 in breast cancer.

BACKGROUND: The benefit of tissue microarray (TMA) is its capability to analyse large numbers of tissue samples in a uniform fashion. This study was designed to evaluate the capability of TMA for analyzing the status of death-associated protein kinase 1 (DAPK1) in breast cancer patient and to explore its potential in the management of breast cancer. PATIENTS AND METHODS: Over a 60-month period, tissue specimens of 99 patients with primary invasive breast cancer were selected. Tissue microarray (TMA) was applied to detect the DAPK1 expression. The data for the other clinicopathologic variables, including age, histological grading, estrogen receptor status and TNM staging were also recorded. RESULTS: Tumor in 11 patients (11.1%) scored 1 for DAPK1 expression, 55 patients (55.6%) scored 2 and 33 (33.3%) scored 3. We found no obvious link between DAPK1 expression and age, histologic grading, primary tumor staging, lymph node status, estrogen receptor and TNM stage. TNM staging was found to be significantly linked to the overall five-year survival rate through multivariate analysis. CONCLUSION: DAPK1 expression did not show any meaningful value in predicting outcome for patients with breast cancer.