Low Expression of A3C and PLP2 Indicating a Favorable Prognosis in Human Gliomas.

The roles of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3C (A3C) in various human malignancies are not consistent. A3C expression is correlated with early-stage breast cancer and is presented as a good prognostic factor; however, it induces fewer therapeutic effects of cytotoxic drugs in low-grade gliomas. To explore the impact of A3C on gliomas, a statistical analysis of several public databases was conducted. The results showed that enhanced A3C expression was associated with advanced tumor grades and poor expression of prognostic factors. Similarly, our in vitro study revealed that glioblastoma (GBM) cell lines had higher A3C mRNA and protein expression than that of normal brain tissue cDNA and lysates. We first performed an immunohistochemical stain (IHC) to prove that gliomas with high A3C expression presented the wild type-Isocitrate dehydrogenase 1 (IDH1), and they had an unfavorable prognosis in human glioma tissues. In addition, the oncological factors associated with A3C expression suggested that DNA repair pathways are important mechanisms for inducing tumorigenesis and chemoresistance in gliomas. Moreover, a significant correlation was observed between A3C expression and proteolipid protein 2  (PLP2). Reactive oxygen species (ROS) -activated PLP2 prevents DNA damage-induced cell apoptosis. Compared to high immunostaining scores for A3C and/or PLP2 expression, combined low immunostaining scores for A3C and PLP2 correlated with improved survival in gliomas; however, the detailed mechanism is to be elucidated. In conclusion, our results not only confirmed A3C played an important role in glioma development, but the A3C IHC test could successfully predict the therapeutic effects and disease prognosis.

The detection of tumor location and lymph node metastasis by aberrant NXPH1 and NXPH2 expressions in pancreatic ductal adenocarcinomas.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease associated with a poor prognosis and high morbidity. Early diagnosis and complete tumor removal are still the principal factors extending life expectancy in PDAC patients. Here, the relationship of neurexophillin 1 (NXPH1) and NXPH2 expressions with clinicopathological parameters of PDAC was evaluated. Immunohistochemical analysis of NXPH1 and NXPH2 was performed in one tissue microarray of 96 surgical specimens, including normal pancreatic duct tissue (n = 5), PDACs at various stages of differentiation (n = 77), and pancreatic neuroendocrine tumors (n = 14). The intensity of both NXPH1 and NXPH2 staining was weak in only a small proportion of benign pancreatic ductal epithelial cells and was significantly higher in most PDAC specimens than in non-neoplastic pancreatic tissue specimens. However, no correlation of the expression of these PDAC biomarkers with tumor grades, T, N, and American Joint Committee on Cancer (AJCC) pathologic stages was established. Contrary to our expectation, the immunohistochemical results of NXPH1 and NXPH2 were inversely correlated with N stage in PDAC. NXPH1 and NXPH2 as PDAC biomarkers may be used to identify patients with this tumor, help delineate appropriate surgical margins, and identify lymph node metastasis in imaging studies.

Effectively α-Terpineol Suppresses Glioblastoma Aggressive Behavior and Downregulates KDELC2 Expression.

BACKGROUND: Glioblastoma (GBM) is notorious for the aggressive behaviors and easily results in chemo-resistance. Studies have shown that the use of herbal medicines as treatments for GBM as limited by the blood-brain barrier (BBB) and glioma stem cells. PURPOSE: The aim of this study was to investigate the relationship between GBM suppression and α-terpineol, the monoterpenoid alcohol derived from Eucalyptus glubulus and Pinus merkusii. STUDY DESIGN: Using serial in-vitro and in-vivo studies to confirm the mechanism of α-terpineol on down-regulating GBM development. METHODS: The 3-[4,5-dimethylthiazol-2-yl)]-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate IC50 of α-terpineol to inhibit GBM cell survival. In order to evaluate the impact of GBM aggressive behaviors by α-terpineol, the analysis of cell migration, invasion and colony formation were implemented. In addition, the ability of tumor spheres and WB of CD44 and OCT3/4 were evaluated under the impression of α-terpineol decreased GBM stemness. The regulation of neoangiogenesis by α-terpineol via the WB of angiogenic factors and human umbilical vein endothelial cells (HUVEC) tube assay. To survey the decided factors of α-terpineol downregulating GBM chemoresistance depended on the impact of O6-methylguanine-DNA methyltransferase (MGMT) expression and autophagy-related factors activation. Additionally, WB and quantitative real-time polymerase chain reaction (qRT/PCR) of KDEL (Lys-Asp-Glu-Leu) containing 2 (KDELC2), endoplasmic reticulum (ER) stress, phosphoinositide 3-kinase (PI3k), mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) cascade signaling factors were examined to explore the mechanism of α-terpineol inhibiting GBM viability. Finally, the orthotopic GBM mouse model was applied to prove the efficacy and toxicity of α-terpineol on regulating GBM survival. RESULTS: α-terpineol significantly suppressed GBM growth, migration, invasion, angiogenesis and temozolomide (TMZ) resistance. Furthermore, α-terpineol specifically targeted KDELC2 to downregulate Notch and PI3k/mTOR/MAPK signaling pathway. Finally, we also demonstrated that α-terpineol could penetrate the BBB to inhibit GBM proliferation, which resulted in reduced cytotoxicity to vital organs. CONCLUSION: Compared to published literatures, we firstly proved α-terpineol possessed the capability to inhibit GBM through various mechanisms and potentially decreased the occurrence of chemoresistance, making it a promising alternative therapeutic option for GBM in the future.

Cytoplasmic CD133 expression is a reliable prognostic indicator of tumor regression after neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer.

BACKGROUND: Despite development in therapeutic strategies, such as neoadjuvant concurrent chemoradiotherapy (CCRT), the prognosis of colorectal cancer remains relatively poor. Cancer stem cells (CSC) with several characteristics can lead to therapeutic resistance. CD133 has been identified as a putative CSC marker in colorectal cancer; however, its functional role still needs elucidation. We verified the role of CD133 with emphasis on expression location and correlated the results of CD133 with clinical outcome in colorectal cancer. METHODS: We used immunohistochemistry to investigate the expression of CD133 in samples from 157 patients with colonic adenocarcinoma and from 76 patients with rectal adenocarcinoma who received neoadjuvant CCRT. We also correlated the expression location of CD133 with the clinicopathological parameters and prognosis. RESULTS: CD133 protein was variably overexpressed in colorectal cancer tissues and was present in three locations: apical and/or endoluminal surfaces, cytoplasm, and lumen. Cytoplasmic CD133 expression level correlated significantly with tumor local recurrence (P = 0.025) and survival of patients with colorectal cancer (P = 0.002), and correlated inversely with tumor regression grading (P = 0.021) after CCRT in patients with rectal cancer. CONCLUSIONS: The expression of CD133 in the cytoplasm is closely associated with local recurrence and patient survival, and may provide a reliable prognostic indicator of tumor regression grading in patients with rectal cancer after CCRT. Cytoplasmic CD133 expression may also help identify the surviving cancer cells in areas with nearly total regression after CCRT.

Discordance between EGFR expression and clinicopathologic parameters of colorectal adenocarcinoma in Taiwan.

Dysregulation of epidermal growth factor receptor (EGFR) has been associated with colorectal cancer, but no evidence shows a relationship of EGFR expression to clinicopathological parameters in colorectal cancer in Taiwan. Immunohistochemical analysis of EGFR, Ki67, and p53 was performed in tissue microarray slides of 9 normal glandular tissues and 150 specimens including 49 well, 58 moderately, and 43 poorly differentiated colorectal adenocarcinomas. Differences in intensity of EGFR immunostaining and the percentages of Ki67 and p53 positive cells between normal and tumor specimens were evaluated using the Student t-test, one-way ANOVA, and linear regression analysis. Intensity of EGFR staining was weak and nuclear expression of Ki67 and p53 was scattered in all 9 control specimens. Expression of Ki67 and p53 but not EGFR was significantly higher in more advanced grades and TNM stages of colorectal adenocarcinoma than in normal controls. The percentages of Ki67 and p53 stained tumor cells were significantly higher in moderately (Ki67: 60.3 ± 6.5, p53: 47.6 ± 3.8) and poorly (Ki67: 61.8 ± 5.3, p53: 55.1 ± 4.1) differentiated tumor cells than in well differentiated (Ki67: 40.8 ± 4.4, p53: 39.8 ± 4.2) tumor cells. Additionally, the Ki67 and p53 staining intensity was also significantly correlated with the more advanced T, N and American Joint Committee on Cancer (AJCC) clinical stage of colorectal adenocarcinoma, suggesting their usefulness as biomarkers of colorectal adenocarcinoma progression. In conclusion, EGFR immunochemistry may not be a good method for pre-treatment evaluation of colorectal adenocarcinoma in Taiwan.

Association between Osteopontin and EGFR Expression with Clinicopathological Parameters in Hepatocellular Carcinoma.

Osteopontin (OPN) and epidermal growth factor receptor (EGFR) are important factors associated with tumor progression, invasion and metastasis in humans. The aim of this study was to assess the correlation of OPN and EGFR expression with hepatocellular carcinoma (HCC) progression. Expression of OPN and EGFR was assessed by immunohistochemistry in 100 HCC specimens. Immunostaining scores (0 to 400) were calculated from the percentage of cells (0 to 100) at each immunostaining intensity and the immunostaining intensity (0 to 4). The average immunostaining score for OPN was correlated with tumor grade (56.1 for grade I, 104.6 for grade II, and 141.2 for grade III; P = 0.023) and T stage (58.6 for stage T1, 85.9 for stage T2, 126.8 for stage T3, and 189.1 for stage T4; P = 0.029). Similarly, the average immunostaining score for EGFR was correlated with tumor grade (80.5 for grade I, 142.1 for grade II, 230.6 for grade III; P = 0.011) and T stage (96.4 for stage T1, 135.5 for stage T2, 221.3 for stage T3, and 261.4 for stage T4; P = 0.026). In addition, OPN and EGFR immunostaining scores were also correlated with M, N, and AJCC stages. In conclusion, higher expression of OPN and EGFR is significantly associated with advanced histological grades, advanced pathological stages and poorer survival rates in HCC. OPN and EGFR may be used as novel biomarkers for diagnosis or monitoring of progression of hepatocellular carcinoma.

Rare gallbladder adenomyomatosis presenting as atypical cholecystitis: case report.

BACKGROUND: Gallbladder adenomyomatosis is a benign condition characterized by hyperplastic change in the gallbladder wall and overgrowth of the mucosa because of an unknown cause. Patients with gallbladder adenomyomatosis usually present with abdominal pain. However, we herein describe a case of a patient with gallbladder adenomyomatosis who did not present with abdominal pain, but with only fever. CASE PRESENTATION: A 34-year-old man presented to our hospital with a fever. No abdominal discomfort was declared. His physical examination showed no abnormalities. Ultrasound of the abdomen revealed thickness of the gallbladder. Acute cholecystitis was diagnosed. The fever persisted even after 1 week of antibiotic therapy. Magnetic resonance imaging of the abdomen showed gallbladder adenomyomatosis with intramural Rokitansky-Aschoff sinuses. Exploratory laparotomy with cholecystectomy was performed. The fever recovered and no residual symptoms were reported at the 3-year follow-up. CONCLUSIONS: Gallbladder adenomyomatosis can present with fever as the only symptom. Although the association between gallbladder adenomyomatosis and malignancy has yet to be elucidated, previous reports have shown a strong association between gallbladder carcinoma and a subtype of gallbladder adenomyomatosis. Surgical intervention remains the first-choice treatment for patients with gallbladder adenomyomatosis.

Expression of LGR8 and related biomarkers in hepatocellular carcinoma: correlation with clinicopathological parameters.

This study aimed to evaluate the relationship between expression of LGR8, VEGF, MMP-2, MMP-9, fascin-1 and cortactin with clinicopathological parameters in hepatocellular carcinoma (HCC). The six biomarkers were investigated immunohistochemically using tissue microarrays of 93 HCC specimens. The tumor cells showed significant expression of LGR8, VEGF, MMP-9, fascin-1 and cortactin, but not of MMP-2. In addition, higher immunostaining scores for LGR8 in HCC showed negative correlation with T and AJCC clinical stages and upregulation of MMP-9, but no correlation with poorer survival rate; cortactin expression is correlated with poorer tumor differentiation in HCC. Thus, our data suggest that higher expression of LGR8 may facilitate tumor invasiveness in the early clinical stage of hepatocellular carcinoma, and synergic effects of cortactin also play a crucial role in the intrahepatic metastasis. Although tumor biological evidence implicates the relaxin-like hormone family as endocrine mediators of critical cellular action in cancer, characterization of target molecules and signaling pathways specific for LGR8 in defined tumor entities and crosstalk of the relaxin receptors with other receptor systems relevant to carcinogenesis will be of significant clinical relevance and may contribute to novel therapeutic strategies against hepatocellular carcinoma.

Suberoylanilide hydroxamic acid induces apoptosis and sub-G1 arrest of 320 HSR colon cancer cells.

BACKGROUND: Histone deacetylases and histone acetyl transferases covalently modify histone proteins, consequentially altering chromatin architecture and gene expression. METHODS: The effects of suberoylanilide hydroxamic acid, a HDAC inhibitor, on 320 HSR colon cells were assessed in 320 HSR colon cancer cells. RESULTS: Concentration and time-dependent inhibition of 320 HSR cell proliferation was observed. Treatment of 320 HSR cells with 5 µM SAHA for 72 h significantly inhibited their growth by 50% as compared to that of the control. Fluorescence-activated cell sorting analysis demonstrated significant inhibition of cell cycle progression (sub-G1 arrest) and induction of apoptosis upon various SAHA concentrations after 48 h. In addition, the anti-apoptosis proteins, survivin and Bcl-xL, were significantly inhibited by SAHA after 72 h of treatment. Immunocytochemistry analysis revealed that SAHA-resistant cells were positive for cyclin A (85%), ki-67 (100%), p53 (100%), survivin (100%), and p21 (90%) expression. Furthermore, a significant increase cyclin A-, Ki-67-, p53-, survivin-, and p21-positive cells were noted in SAHA-resistant tumor cells. CONCLUSION: Our results demonstrated for the first time in 320 HSR colon adenocarcinoma cells that SAHA might be considered as an adjuvant therapy for colon adenocarcinoma.

Fascin, cortactin and survivin expression of melanocytic neoplasms and association with clinicopathological parameters and anatomic locations in Chinese people.

Distinct genetic aberrations between melanomas in different anatomical locations have been confirmed in recent years. However, the associations between immunohistochemical expression, tumor sites, and clinical parameters are not clear. We examined the correlation of protein expression of fascin, cortactin and survivin with clinicopathological parameters and lesion locations in patients with cutaneous melanoma. We collected 170 melanocytic lesions, including 106 cutaneous malignant melanoma (MM) from acral (AM) and non-acral (NAM) sites, 24 dysplastic nevi (DN), and 40 common melanocytic nevi (CMN). Tissue micro arrays were constructed and immunohistochemical expression for cortactin, fascin, and survivin was assessed with correlation with clinical parameters. Cytoplasmic immunostaining for fascin was found to be significantly higher in CMN than DN, and survivin staining was significantly higher in DN than MM. Positive nuclear immunoreactivity for survivin was seen in a large subset of melanomas but much less frequently in CMN and DN. In addition, nuclear survivin immunoreactivity was significantly more common in NAM than in AM. Nuclear survivin staining in patients with NAM was significantly correlated with poor survival. The significantly different expression of immunoreactivities (nuclear survivin) between AM and NAM and the different mortality risks of melanomas on acral versus non-acral sites might change site-specific therapeutic concepts in melanoma.

Chromophobe renal cell carcinoma with osteosarcoma differentiation: case report and literature review.

Chromophobe renal cell carcinoma is a distinct subtype of renal cell carcinoma that is well known for its relatively good prognosis. When it presents with sarcomatoid differentiation, necrosis of the sarcomatoid area or angiolymphatic invasion, it becomes a highly aggressive neoplasm. The presence of osteosarcoma-like elements in sarcomatoid chromophobe renal cell carcinoma is very rare as only 5 cases have been reported previously. We present a 6th case of sarcomatoid chromophobe renal cell carcinoma, which had an osteosarcoma differentiation component. However, the correlation between the presence of heterologous elements and prognosis is unknown because of the rarity of this phenomenon.

Cortactin, fascin and survivin expression associated with clinicopathological parameters in brain gliosarcoma.

Gliosarcoma is a very rare primary neoplasm of the central nervous system classified as a variant of glioblastoma. Cortactin, fascin and survivin have been found in several human cancers to play important roles in tumor progression, but the expression pattern of these biomarkers in gliosarcoma is unclear. Immunostaining for cortactin, fascin and survivin was assessed in 6 surgical specimens of brain gliosarcoma, and the relationship between the expression of these biomarkers and tumor size or clinical parameters were examined. Five of our six patients with gliosarcoma survived 3-17 months. One patient is still alive for more than 24 months. The mean immunostaining scores for cortactin were significantly higher in the gliomatous (score 236.6 +/- 45.4) and sarcomatous (score 233.3 +/- 51.4) components than in normal brain tissues (score 21.6 +/- 6.6). The mean cytoplasmic immunostaining scores for fascin and survivin were also significantly higher in the gliomatous and sarcomatous components than in normal brain tissues. In addition, survivin was also stained in the nucleus of tumor cells. Linear regression analysis showed that fascin score in the gliomatous component was significantly associated with tumor size (R = 0.69) and the fascin score in the sarcomatous component was significantly associated with patient's age (R = 0.87). In addition, the survivin cytoplasmic scores in the gliomatous and sarcomatous components were inversely associated with tumor size. Our results demonstrated that over-expression of cortactin, fascin and survivin is associated with malignant transformation of brain gliosarcoma. Development of drugs that target cortactin, fascin and survivin expression may be therapeutic to patients with gliosarcoma.

Prognostic significance of global histone modifications in resected squamous cell carcinoma of the esophagus.

Patterns of global histone modifications have been recently suggested as outcome predictors in cancer patients. To date, there has been no report on the prognostic significance of global histone modifications in esophageal squamous cell carcinoma. We investigated the role of global histone modification as outcome predictor in patients undergoing esophagectomy for esophageal squamous cell carcinoma. A retrospective clinicopathologic analysis was undertaken of 97 patients with esophageal squamous cell carcinoma who recovered from esophagectomy. Immunohistochemical expression of five histone modification markers, acetylated histone 3 lysine 18 (H3K18Ac), acetylated histone 4 lysine 12 (H4K12Ac), dimethylated histone 4 arginine 3 (H4R3diMe), dimethylated histone 3 lysine 4 (H3 K4diMe), and trimethylated histone 3 lysine 27 (H3K27triMe) was assessed in paraffin-embedded tumor samples. Results were analyzed in relation to patients' clinicopathologic parameters. There was a positive relationship between tumor differentiation and H3K18Ac (P<0.001), H4R3diMe (P=0.003), and H3K27triMe (P<0.001). Expression of H3K27triMe correlated positively with nodal (N) status (P=0.012) and stage (P=0.025). Univariate analysis showed that better survival in patients with low expression of H3K18Ac (P=0.038) and H3K27triMe (P=0.003). Multivariate analysis showed that nodal status, metastasis status (M), and expression of H3K27triMe predicted survival independently (P<0.001, P=0.016, and 0.048, respectively). Low expression of H3K18Ac and H3K27triMe correlated with better prognosis of patients with esophageal squamous cell carcinoma, especially for those of early stages. We hypothesize that expression of H3K27triMe may be considered as a significant survival predictor for patients with esophageal squamous cell carcinoma.

Expression of survivin and cortactin in colorectal adenocarcinoma: association with clinicopathological parameters.

OBJECTIVE: Survivin and cortactin are factors that promote tumor progression. We tested the hypothesis that survivin and cortactin expressions correlate with the clinico-pathological parameters of colorectal adenocarcinomas and survival time. METHODS: Immunohistochemical analysis of survivin and cortactin were performed using tissue microarrays of 119 specimens from 18 well, 50 moderately, and 27 poorly differentiated colorectal adenocarcinomas and 24 colorectal adenomas with dysplasia. As control, 10 specimens of normal colorectal epithelia were included. RESULTS: The percentage of cells immunostained and the immunostaining scores for survivin and cortactin were all significantly higher in well-, moderately, and poorly differentiated colorectal adenocarcinomas than in normal colorectal epithelia. The survivin immunostaining score was significantly correlated with T, M, and AJCC/TNM stages (p < 0.05). For cortactin, the score was significantly correlated with T and M stages (p < 0.05). Higher survivin immunostaining score was associated with higher mortality. CONCLUSIONS: Higher expression of survivin and cortactin correlates significantly with tumor stages and shorter survival time. Survivin and cortactin may be good biomarkers of aggressiveness of colorectal adenocarcinomas. Our findings require validation in independent cohorts and these data support the potential targeting of survivin and cortactin for the development of novel therapeutic strategies.

Expression of cortactin and survivin in renal cell carcinoma associated with tumor aggressiveness.

PURPOSE: We tested the hypothesis that the expression of cortactin and survivin in renal cell carcinomas (RCCs) correlates with more advanced stages of the disease. METHODS: Immunohistochemical analysis of cortactin and survivin expression (scored on a scale of 0-400) was performed in 124 renal cell carcinomas including clear cell renal cell carcinoma (CRCC), papillary RCC (PRCC), CRCC with sarcomatoid differentiation (SRCC), chromophobe RCC (ChRCC), and CRCC with granular cell differentiation (GRCC). RESULTS: Higher cortactin scores in CRCC were significantly correlated with higher T (p = 0.021) and N stages (p = 0.036), and nuclear grade (p = 0.012). Higher cortactin immunostaining scores were associated with higher mortality (p = 0.035). In addition, the survivin scores were significantly higher in the more aggressive GRCC and SRCC than in CRCC, suggesting a significant role of survivin expression in transformation of tumor cells to a more malignant phenotype. CONCLUSIONS: Higher expression of cortactin and survivin significantly correlated with advanced clinicopathological stage. Our findings support the potential targeting of survivin and cortactin for the development of novel therapeutic strategies for renal cell carcinoma.

Matriptase and survivin expression associated with tumor progression and malignant potential in breast cancer of Chinese women: tissue microarray analysis of immunostaining scores with clinicopathological parameters.

OBJECTIVE: The aim of this study was to examine the expression of matriptase and survivin in breast carcinoma and correlate with clinicopathological parameters. METHODS: Immunohistochemical analysis of matriptase and survivin were performed in tissue microarray slides of 290 cases, including 11 normal breast tissue; 27 fibrocystic disease; 17 fibroadenoma; 6 atypical ductal hyperplasia; 39 ductal carcinoma in situ, low grade (DCIS, low grade); 39 ductal carcinoma in situ, high grade (DCIS, high grade); 27 invasive ductal carcinoma, grade I (IDC, grade I); 78 invasive ductal carcinoma, grade II (IDC, grade II); and 46 invasive ductal carcinoma, grade III (IDC, grade III). RESULTS: The average immunostaining scores of matriptase were 44.1 in normal breast tissue, 52.7 in fibrocystic disease, 76.5 in fibroadenoma, 81.7 in atypical ductal hyperplasia, 133.7 in low-grade DCIS, and 155.8 in high-grade DCIS. Among 151 breast IDC cases, the average immunostaining scores of matriptase were 172.7 in grade I, 211.7 in grade II, and 221.2 in grade III. Additionally, the average immunostaining scores of surviving also correlate with tumor grades and stages. CONCLUSIONS: Higher expressions of matriptase and survivin correlate significantly with clinicopathological parameters in breast cancer and the malignant potential in premalignant lesions. In addition, higher survivin expression had poorer prognosis of breast IDC cases.

Association of cortactin, fascin-1 and epidermal growth factor receptor (EGFR) expression in ovarian carcinomas: correlation with clinicopathological parameters.

Cortactin, fascin-1 and EGFR are recognized as important factors in tumor progression. We tested the hypothesis that cortactin, fascin-1 and EGFR expression correlates with clinicopathological parameters of the four most common ovarian surface epithelial carcinomas--serous cystadenocarcinoma, mucinous cystadenocarcinoma, endometrioid adenocarcinoma, and clear cell carcinoma. Immunohistochemical analysis of cortactin, fascin-1 and EGFR was performed using tissue microarrays of 172 specimens comprising 69 serous cystadenocarcinomas, 44 mucinous cystadenocarcinomas, 45 endometrioid adenocarcinomas and 14 clear cell carcinomas. All ovarian carcinomas showed significant expression of cortactin, fascin-1 and EGFR in staining intensity, tumor percentages and immunostaining scores. In addition, higher immunostaining scores of fascin-1 correlated with more advanced cancer stages (TNM), poorer histological differentiation and poorer survival rate of mucinous cystadenocarcinoma. Similarly, higher immunostaining scores of cortactin correlated with T stages and histological differentiation of serous cystadenocarcinoma. The immunostaining scores of EGFR did not correlate with TNM stages, tumor differentiation or prognosis in the four ovarian surface epithelial carcinomas. Our findings suggest that cortactin and fascin-1 may serve as good biomarkers in evaluating aggressiveness of ovarian serous and mucinous cystadenocarcinoma. And the pharmacological inhibitors of fascin-1 activity may slow down tumor progression and prolong survival time in patients with mucinous cystadenocarcinoma.

Expression of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF)-D as outcome predictors in resected esophageal squamous cell carcinoma.

Hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF) are important angiogenic factors in human cancers. Relative to VEGF-C, prognostic significance of VEGF-D expression and its association with HIF-1alpha expression remain elusive in esophageal squamous cell cancer (ESCC). We studied expression of HIF-1alpha and VEGF-D using immunohistochemistry in 85 resected ESCC specimens and correlated results with patients' clinicopathologic parameters and survival. Association between expression of HIF-1alpha and VEGF-D was investigated using a concordance analysis. High expression of HIF-1alpha and VEGF-D was observed in 52 (61.2%) and 56 (65.9%) patients, respectively. HIF-1alpha expression correlated well with tumor stage (P = 0.041), whereas VEGF-D expression correlated with tumor stage (P = 0.027) and N status (P = 0.019). Groups of high HIF-1alpha and VEGF-D showed worse survivals than those of low expression (P = 0.002 and 0.001, respectively). Multivariate analysis supported expression of HIF-1alpha and VEGF-D as significant survival predictors (P = 0.044 and 0.035, respectively). A concordance rate of 69.5% was observed between expression of HIF-1alpha and VEGF-D. In conclusion, protein expression of HIF-1alpha and VEGF-D are independent prognostic predictors. An association between expression of HIF-1alpha and VEGF-D suggests that these two angiogenic factors are essential in progression of ESCC.