Chih-Kung Lin

The expression of six biomarkers in the four most common ovarian cancers : correlation with clinicopathological parameters

This study aimed to evaluate the relationship of fascin‐1, matrix metalloproteinase (MMP)‐2, MMP‐9, cortactin, survivin, and epidermal growth factor receptor (EGFR) expression with clinicopathological parameters for the four most common ovarian surface epithelial carcinomas. Six biomarkers were investigated immunohistochemically using tissue microarrays of 185 specimens including 79 serous cystadenocarcinomas, 47 mucinous cystadenocarcinomas, 45 endometrioid adenocarcinomas, and 14 clear cell carcinomas. The four most common ovarian carcinomas showed significant expression of fascin‐1, cortactin, survivin, and EGFR, but not of MMP‐2 and MMP‐9. In addition, higher immunostaining scores for fascin‐1 in mucinous cystadenocarcinomas correlated with T stage, N stage, American Joint Committee on Cancer AJCC clinical stage, and a poorer survival rate; for cortactin in serous cystadenocarcinomas correlated with T stage; for cortactin in clear cell carcinomas correlated with T and clinical AJCC stages; and for survivin in clear cell carcinomas correlated with T stage and AJCC clinical stage. In addition, higher immunostaining scores for fascin‐1, cortactin, and survivin correlated with poorer tumor differentiation in serous, mucinous, and endometrioid adenocarcinomas. Thus, the expression of fascin‐1, cortactin, and survivin may be helpful in evaluating the aggressiveness of ovarian mucinous, serous, and clear cell adenocarcinoma. Additionally, the expression of fascin‐1 may be an independent prognostic risk factor in mucinous cystadenocarcinoma.

Triptolide exerts anti-tumor effect on oral cancer and KB cells in vitro and in vivo

Triptolide (TPL), a diterpenoid triepoxide purified from the Chinese herb Tripterygium wilfordii Hook F, has been reported to potentiate the anti-tumor effect in various cancer cells. However, the effect of TPL on oral cancers is not yet evaluated. Herein we first demonstrate that TPL induces prominent growth inhibition and apoptosis in two oral cancer cell lines, SCC25 and OEC-M1 and in KB cells. Our results indicate that TPL induces a dose-dependent apoptosis of these cells at nanomolar concentration. Apoptosis signalings are both activated through time upon TPL treatment detected by elevated caspase-3, 8, 9 activities. In xenograft tumor mouse model, TPL injection successfully inhibits the tumor growth via apoptosis induction which was demonstrated by TUNEL assay. These results demonstrate that TPL exerts anti-tumor effect on oral cancer and KB cells and suggest further the potential of TPL combining with other chemotherapeutic agents or radiotherapy for advanced oral cancer.

Cortactin, fascin, and survivin expression associated with clinicopathological parameters in esophageal squamous cell carcinoma

Cortactin, fascin, and survivin have been documented in several human cancers and play important roles in tumor progression. We collected 57 surgical specimens, including esophageal squamous cell carcinomas (SqCC; 7 well-differentiated, 15 moderately differentiated, and 24 poorly differentiated), 3 dysplasias, and 8 normal esophageal tissues. Tissue microarrays were constructed and the immunostaining scores for cortactin, fascin, and survivin were assessed. In 46 SqCC specimens, we examined the relationship between the expression of three biomarkers and tumor differentiation or clinical parameters. Higher immunostaining scores for cortactin, fascin, and survivin correlated positively with tumor differentiation of esophageal SqCC. Univariate survival analysis showed significantly worse prognosis in patients with high scores of cortactin (>or=290), fascin (>or=245), and survivin (score >or= 175), poor differentiation, T4 stage, positive for lymph node metastasis, and positive for distant metastasis. In multivariate survival analysis, high scores of survivin (>or=175) and poor differentiation were independent risk factors for worse prognosis. Our results demonstrated that higher expression of survivin may be related to tumor progression and it is an independent risk factor for poor survival time of esophageal SqCC. Survivin may be a good biomarker to be applied in clinic to predict the prognosis of esophageal SqCC.

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.

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.

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.

The association of osteopontin and LMX1A expression with World Health Organization grade in meningiomas and gliomas

Tsai W‐C, Lee H‐S, Lin C‐K, Chen A, Nieh S & Ma H‐I 
(2012) Histopathology 61, 844–856

Osteopontin predicts the behaviour of atypical meningioma

Lin C‐K, Tsai W‐C, Lin Y‐C & Hueng D‐Y 
(2012) Histopathology 60, 320–325 
Osteopontin predicts the behaviour of atypical meningioma

The correlation of cortactin and fascin-1 expression with clinicopathological parameters in pancreatic and ampulla of Vater adenocarcinoma

Cortactin and fascin‐1 are important factors affecting progression and metastasis of carcinomas. We tested the hypothesis that cortactin and fascin expression has significant correlation with clinicopathological parameters in pancreatic and ampulla of Vater adenocarcinomas. Immunohistochemical analysis of cortactin and fascin‐1 was performed in 50 pancreatic and 40 ampulla of Vater adenocarcinomas. The specimens were from 29 R0, 8 R1, and 13 palliative resections of pancreatic adenocarcinomas and 18 R0, 14 R1, and 8 palliative resections of ampulla of Vater adenocarcinomas. ‘R0’ resection is defined by complete removal of the tumor and histologically negative surgical margins and ‘R1’ resection indicates the presence of microscopically residual disease at the surgical margins. The level of expression was assessed by scoring the intensity of cytoplasmic or membranous immunostaining on a 4‐point scale. Higher immunostaining scores of cortactin and fascin‐1 were both significantly correlated with histological grade, American Joint Committee on Cancer (AJCC) stage, and survival rate in all patients. In conclusion, overexpression of cortactin and fascin‐1 implies poorer tumor differentiation, advanced AJCC stage, and shorter survival rate in pancreatic and ampulla of Vater adenocarcinomas.

Triptolide represses oral cancer cell proliferation, invasion, migration, and angiogenesis in co-inoculation with U937 cells

ObjectivesAdvanced oral cancer is a major public health concern because of a lack of effective prevention and treatment. Triptolide (TPL), a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii, has been demonstrated to possess strong anticancer properties. In this study, we investigated whether TPL exerts anticancer effects on the tumor microenvironment of head and neck squamous cell carcinoma (HNSCC).Materials and methodsHuman macrophage-like U937 cells were co-inoculated with oral cancer SAS cells in a noncontact transwell coculture system. Cytokine expression was detected using ELISA, and cell proliferation was detected using methylene blue. RNA levels were detected using qPCR. Protein levels were detected using Western blot analysis. In vivo experiments involved using xenografted NOD/SCID mice.ResultsOur results demonstrated that TPL inhibited the growth of SAS cells co-inoculated with U937 cells in vitro and in vivo. TPL inhibited the invasion, migration ability, and angiogenesis of SAS cells co-inoculated with U937 cells. Expression of cytokines IL-6, IL-8, and TNF-α was induced by co-inoculation, but TPL repressed their expression.ConclusionTPL suppressed the expression of cytokines IL-6, IL-8, and TNF-α, as well as tumor growth, invasion, migration, and angiogenesis in the co-inoculation of human tongue cancer cells with macrophage-like U937 cells.Clinical relevanceTPL is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating tumor-associated macrophages in a tumor microenvironment of HNSCC.