Lifang Fan

Caveolin-1 expression level in cancer associated fibroblasts predicts outcome in gastric cancer.

Aims Altered expression of epithelial or stromal caveolin-1 (Cav-1) is observed in various types of human cancers. However, the clinical significance of Cav-1 expression in gastric cancer (GC) remains largely unknown. The present study aims to explore the clinicopathological significance and prognostic value of both tumor cells and cancer associated fibroblasts (CAFs) Cav-1 in GC. Methods and Results Quantum dots immunofluorescence histochemistry was performed to examine the expression of Cav-1 in 20 cases of gastritis without intestinal metaplasia (IM), 20 cases of gastritis with IM and 286 cases of GC. Positive rates of epithelial Cav-1 in gastritis without IM, gastritis with IM and GC showed a decreasing trend (P = 0.012). Low expression of Cav-1 in CAFs but not in tumor cells was an independent predictor of poor prognosis in GC patients (P = 0.034 and 0.005 respectively in disease free survival and overall survival). Cav-1 level in tumor cells and CAFs showed no significant correlation with classic clinicopathological features. Conclusions Loss of epithelial Cav-1 may promote malignant progression and low CAFs Cav-1 level herald worse outcome of GC patient, suggesting CAFs Cav-1 may be a candidate therapeutic target and a useful prognostic marker of GC.

Diagnostic utility of PAX8, TTF-1 and napsin A for discriminating metastatic carcinoma from primary adenocarcinoma of the lung.

Abstract TTF-1 and napsin A are useful biomarkers for differentiating primary lung adenocarcinoma from metastatic tumors. Studies have shown, however, that TTF-1 and napsin A also can be expressed in extrapulmonary carcinomas, and that a small fraction of primary lung adenocarcinomas do not co-express these two markers. We attempted to determine whether a tissue-specific transcriptional factor, PAX8, can help determine primary sites of lung carcinomas. Immunohistochemical stains for PAX8, TTF-1 and napsin A were performed on 103 cases of metastatic lung carcinomas from a variety of origins and 120 cases of primary lung adenocarcinomas. Our data demonstrated that all 103 metastatic carcinomas were negative for napsin A, while 14 (13.6%; four thyroid, two endometrium, three colon, one prostate, one salivary adenoid cystic, two renal cell carcinomas, and one ovary) showed weak to strong TTF-1 nuclear staining in 5–60% of the tumor cells. All primary lung adenocarcinomas were negative for PAX8, whereas 46 (44.7%) metastatic carcinomas from the kidney (29/33), ovary (6/8), endometrium (5/5), endocervix (1/1), thyroid (4/5) and urinary tract (1/3) were positive for PAX8. Our data demonstrate that of combined use of PAX8, TTF-1 and napsin A is reliable to separate reliably lung primary from metastatic tumors.

Expression of putative stem cell genes Musashi-1 and β1-integrin in human colorectal adenomas and adenocarcinomas

Background and aimsRecent studies revealed that Musashi-1and β1-integrin were putative stem cell genes. Overexpressions of Musashi-1 and β1-integrin have been reported in some tumor tissues and cell lines. This study was to detect expressions of the two genes in colorectal adenomas and carcinomas and to analyze the correlation between Musashi-1 and β1-integrin.MethodsMusashi-1 and β1-integrin immunoreactivity was studied immunohistochemically in tissue microarray-based samples containing 69 colorectal adenocarcinomas, eight normal mucosa, and eight adenomas, and their messenger RNA (mRNA) expression level was detected by RT-PCR in resected specimens including the three types of tissue.ResultsA percentage of 66.7% (46/69) and 59.2% (41/69) of colorectal adenocarcinomas were immunoreactive with Musashi-1 and β1-integrin, respectively. The expressions of Musashi-1 and β1-integrin protein were significantly higher in tissue samples of stage III than those of stage I-II (P = 0.0252; P = 0.0018, respectively). β1-integrin expression was higher in group of adenocarcinomas than that of adenomas (P = 0.0276). Musashi-1 expression was closely correlated with β1-integrin (rs = 0.631, P = 0.0001). Significant differences of Musashi-1 and β1-integrin mRNA expression levels were found between the normal colorectal mucosa, adenoma, and adenocarcinoma tissues (P = 0.01; P = 0.03, respectively).ConclusionsMusashi-1 and β1-integrin may be involved in human colorectal tumor carcinogenesis and progression. Our observations also indicate the need for further investigations to test in vivo whether cells with these markers have stem cell properties.

Li-cadherin is Inversely Correlated with Galectin-3 Expression in Gastric Cancer

The aims of this study were to examine the expressions of Li-cadherin and Galectin-3 in gastric cancer, and the correlation between Li-cadherin and Galectin-3 in gastric cancer was also analyzed. The present study investigated the expression level of Li-cadherin and Galectin-3 by immunohistochemistry and semiquantitative polymerase chain reaction (PCR), and correlated this with clinicopathologic parameters in 91 cases of gastric cancer. The correlation between expression levels of Li-cadherin and Galectin-3 was analyzed by Spearman correlation analysis. The expression level of Li-cadherin mRNA was correlated to differentiation and lymph node metastasis, and the expression level of Galectin-3 was related to TNM staging, differentiation and lymph node metastasis. On Spearman correlation analysis, a definitive negative correlation was found between the expression levels of Li-cadherin and Galectin-3 in gastric cancerous tissues. We postulate that interaction between Li-cadherin and Galectin-3 may play an important role in the development of gastric cancer.

Differential expression and function of the caveolin-1 gene in non-small cell lung carcinoma

This study was designed to clarify the function of caveolin-1 (Cav-1) in the development of lung cancer by investigating the mutation and protein expression of the Cav-1 gene in non-small cell lung carcinoma (NSCLC). Quantum dot immunofluorescence histochemistry was used to evaluate Cav-1 protein expression and subcellular localization in the lung cancer tissue microarray including 140 cases of lung cancer and 20 cases of non-cancerous lung tissue. Mutation of the Cav-1 gene in exon 1 and exon 3 was detected by polymerase chain reaction-single strand conformation polymorphism and sequencing. The positive rates of Cav-1 expression were 49.3% (69/140) in NSCLC group, significantly lower than the 100% (20/20) rate in the control group. Adenocarcinomas (16.7%), adenosquamous carcinomas (38.4%), squamous cell carcinomas (67.1%) and large cell lung cancers (66.7%) displayed Cav-1 positive staining, suggesting a gradient of Cav-1 expression according to tumor histotype-related aggressiveness. High-expression of Cav-1 protein was statistically correlated with pathologic TNM stage and lymph node metastasis. No mutation could be detected in exon 1 and exon 3 from all Cav-1 protein negative expression of NSCLC samples. Cav-1 immunoreactivity in lung cancer is histotype-dependent, increased Cav-1 expression indicates the malignant progression and high invasion features of NSCLCs. Deregulation of Cav-1 expression in NSCLCs may not correlate with mutation.

Apoptosis of human colorectal carcinoma cells is induced by blocking hepatoma-derived growth factor

Hepatoma-derived growth factor (HDGF) is a novel multifunctional growth factor that elicits pleiotropic effects on biological processes such as lung remodeling and renal development. Recent studies demonstrated that HDGF is related to tumor proliferation, invasion, angiogenesis, and apoptosis. However, the molecular mechanism of HDGF’s involvement in apoptosis remains to be clarified. In this study, we first analyze the role of HDGF in colorectal carcinoma (CRC) progression by immunohistochemistry. Then we used small interference RNA (HDGF-siRNA) to block HDGF and assessed its effect on inducing apoptosis of CRC loVo cells. Apoptosis was detected using flow cytometry (FCM), DNA ladder analysis, and Hoechst 33258 staining. In addition, the expression levels of some apoptosis-related proteins were examined by western blot. The result showed that HDGF expression gradually increased in the colorectal carcinogenesis process. Further studies demonstrated that knock-down of HDGF can down-regulate the survivin, activate the mitochondrial pathway, and induce apoptosis in loVo cells. These findings suggest that HDGF is involved in colorectal carcinogenesis process. Further blocking HDGF exhibits potent pro-apoptotic properties in colon cancer cells. Thus, HDGF might be a potential therapeutic target for human colorectal cancer. These findings may have major implications in the treatment of colorectal cancer.

Quantum Dots-Based Immunofluorescent Imaging of Stromal Fibroblasts Caveolin-1 and Light Chain 3B Expression and Identification of Their Clinical Significance in Human Gastric Cancer

Caveolin-1 (Cav-1) expression deficiency and autophagy in tumor stromal fibroblasts (hereafter fibroblasts) are involved in tumor proliferation and progression, particularly in breast and prostate cancer. The aim of this study was to detect the expression of fibroblastic Cav-1 and LC3B, markers of autophagy, in gastric cancer (GC) and to analyze their clinical significances. Furthermore, because Epstein-Barr virus (EBV)-associated GC (EBVaGC) is a unique subtype of GC; we compared the differential expression of fibroblastic Cav-1 and LC3B in EBVaGC and non-EBVaGC. Quantum dots (QDs)-based immunofluorescence histochemistry was used to examine the expression of fibroblastic Cav-1 and LC3B in 118 cases of GC with adequate stroma. QDs-based double immunofluorescence labeling was performed to detect the coexpression of Cav-1 and LC3B proteins. EBV-encoded small RNA was detected by QDs-based fluorescence in situ hybridization to identify EBVaGC. Multivariate analysis indicated that low fibroblastic Cav-1 level was an independent prognosticator (p = 0.029) that predicted poorer survival of GC patients. Positive fibroblastic LC3B was correlated with lower invasion (p = 0.032) and was positively associated with Cav-1 expression (r = 0.432, p < 0.001). EBV infection did not affect fibroblastic Cav-1 and LC3B expression. In conclusion, positive fibroblastic LC3B correlates with lower invasion, and low expression of fibroblastic Cav-1 is a novel predictor of poor GC prognosis.

Interobserver and intraobserver variability in evaluating vascular invasion in hepatocellular carcinoma.

Background and Aim:  Hepatocellular carcinoma (HCC) is unique in that the presence of vascular invasion significantly changes tumor stage. Even though searching for vascular invasion is a common practice in surgical pathology, there appears to be a great variation among pathologists in its recognition. This study was designed to assess whether HCC could be accurately staged using vascular invasion as a staging parameter.

Lymph node retrieval from colorectal resection specimens for adenocarcinoma: is it worth the extra effort to find at least 12 nodes?

Aim  Retrieval of a minimum of 12 lymph nodes has been recommended for adequately staging a node‐negative colorectal cancer (CRC). This study was designed to determine whether the extra effort expended to recover more nodes for histological examination improves the accuracy of staging.

Expression of Cav-1 in tumour cells, rather than in stromal tissue, may promote cervical squamous cell carcinoma proliferation, and correlates with high-risk HPV infection

Altered expression of caveolin-1 (Cav-1) is observed in various types of cancers. However, little research has been reported regarding the correlation between the expression of Cav-1 and cervical cancer. Here, we investigated the clinical significance of Cav-1 expression using quantum dot (QD)-based immunofluorescence staining in cervical cancer and its correlation with high-risk human papilloma virus (HPV) infection detected by chromogenic in situ hybridization. Our results showed that the positive rates of Cav-1 protein in normal cervical mucosa, CIN, cervical adenocarcinoma and SCC were: 0, 33, 19 and 55%, respectively. The differences in Cav-1 protein expression in cervical SCC compared to the other three groups were all statistically significant. Absence of stromal Cav-1 protein in 58 cases of cervical SCC was 67%. The positive rates of the Cav-1 protein in tumour and stromal cells of cervical SCC were not correlated with clinicopathological parameters. In the cervical SCC tissues, Cav-1 expression in tumour cells was not associated with stromal Cav-1 expression, but a positive correlation existed with the PCNA protein and high-risk of HPV infection. The results presented here suggest that expression of Cav-1 in the tumour cells, rather than in the stromal tissue surrounding the tumour, may promote cervical SCC cell proliferation, and correlates with high-risk HPV infection.