Association of Cortactin and Fascin-1 Expression in Gastric Adenocarcinoma: Correlation With Clinicopathological Parameters

Cortactin and fascin-1 are important factors in tumor progression. We tested the hypothesis that cortactin and fascin-1 expression correlates with clinicopathological parameters of gastric adenocarcinoma. Immunohistochemical analysis of cortactin and fascin-1 was done using tissue microarrays of 100 surgical specimens, including 20 well-differentiated, 20 moderately differentiated, and 60 poorly differentiated gastric adenocarcinomas. Among the 20 well-differentiated gastric adenocarcinomas, 15 cases (75%) showed negative or weak staining (1+); 5 cases (25%) had moderate (2+) or strong (3+) cortactin expression. Among the 60 poorly differentiated gastric adenocarcinomas, more than three-quarters of the cases (76.7%) had moderate or strong cortactin expression; 14 cases (23.3%) had weak staining. Of 20 well-differentiated gastric adenocarcinoma cases, 14 (70%) showed negative or weak staining of fascin-1, whereas nearly one-third (30%) had moderate or strong expression. Among the 60 poorly differentiated gastric adenocarcinomas, 32 (53.3%) exhibited moderate or strong fascin-1 expression; fewer than half of the cases showed negative or weak staining. Higher intensity of cortactin and fascin-1 staining correlated directly with more-advanced cancer stages (TNM) and inversely with survival rates. Our findings suggest the possibility that pharmacological inhibitors of cortactin and fascin-1 activity may slow down tumor progression and prolong survival time in patients with gastric adenocarcinomas.

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Clinicopathological Profiling of Lung Carcinoids with a Ki67 Index > 20%

Neuroendocrinology ◽

10.1159/000495806 ◽

2018 ◽

Vol 108 (2) ◽

pp. 109-120 ◽

Cited By ~ 11

Author(s):

Atsuko Kasajima ◽

Björn Konukiewitz ◽

Naomi Oka ◽

Hiroyoshi Suzuki ◽

Akira Sakurada ◽

...

Keyword(s):

Survival Rates ◽

Disease Free Survival ◽

Japanese Patients ◽

Clinicopathological Parameters ◽

Neuroendocrine Neoplasms ◽

Free Survival ◽

Tumor Group ◽

Poorly Differentiated ◽

Well Differentiated ◽

Disease Free

The clinicopathological features of lung neuroendocrine neoplasms (NEN) with a high proliferative index at the border area between atypical carcinoid and neuroendocrine carcinoma have not been investigated so far. The aim of this study was, therefore, to search for lung NENs which are well differentiated but show Ki67 values that overlap with those of poorly differentiated (PD)-NENs. Resected lung NENs from 244 Japanese patients were reviewed, and Ki67 indices were assessed in all tumors. The data were then correlated to clinicopathological parameters and patient outcome. Among 59 (24%) well-differentiated (WD)-NENs and 185 (76%) lung PD-NENs, 7 were defined as WD-NENs with Ki67 indices > 20%. The Ki67 indices of these tumors (mean 29%, range 24–36) were significantly lower than those of PD-NENs (mean 74%, range 34–99). All WD-NENs with Ki67 > 20% lacked abnormal p53 and loss of retinoblastoma 1 (Rb1) expression. In contrast, many PD-NENs expressed p53 (48%) and showed loss of Rb1 (86%). The 2- and 5-year disease-free survival rates in WD-NEN patients with Ki67 > 20% were lower than those of WD-NEN patients with Ki67 ≤20% (p < 0.01 for disease-free and overall survival). No statistical differences were detected between outcome of WD-NEN patients with Ki67 > 20% and those of PD-NEN. It is concluded that WD-NEN patients with Ki67 > 20% share the morphological and immunohistochemical features of WD-NEN patients with Ki67 ≤20%, but they have a worse prognosis, suggesting that this tumor group requires particular attention in future classifications and probably new therapeutic regimes.

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Expression of Survivin and Cortactin in Colorectal Adenocarcinoma: Association with Clinicopathological Parameters

Disease Markers ◽

10.1155/2009/821543 ◽

2009 ◽

Vol 26 (1) ◽

pp. 9-18 ◽

Cited By ~ 24

Author(s):

Ying-Yu Lee ◽

Cheng-Ping Yu ◽

Chih-Kung Lin ◽

Shin Nieh ◽

Kuo-Feng Hsu ◽

...

Keyword(s):

Survival Time ◽

Immunohistochemical Analysis ◽

Tissue Microarrays ◽

Colorectal Adenomas ◽

Clinicopathological Parameters ◽

Tumor Stages ◽

Poorly Differentiated ◽

Novel Therapeutic Strategies ◽

Colorectal Adenocarcinomas ◽

Immunostaining Score

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.

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Overexpression of Fascin-1 in Advanced Colorectal Adenocarcinoma: Tissue Microarray Analysis of Immunostaining Scores with Clinicopathological Parameters

Disease Markers ◽

10.1155/2007/685163 ◽

2007 ◽

Vol 23 (3) ◽

pp. 153-160 ◽

Cited By ~ 20

Author(s):

Wen-Chiuan Tsai ◽

You-Chen Chao ◽

Lai-Fa Sheu ◽

Junn-Liang Chang ◽

Shin Nieh ◽

...

Keyword(s):

Immunohistochemical Analysis ◽

Tissue Microarrays ◽

Colorectal Adenomas ◽

Actin Binding ◽

Clinicopathological Parameters ◽

Grade Ii ◽

Poorly Differentiated ◽

Colorectal Adenocarcinomas ◽

Tissue Microarray Analysis ◽

Dysplastic Change

Objective:Fascin-1 is an actin-binding protein that promotes cell proliferation, adhesion and motility. We tested the hypothesis that fascin-1 expression correlates with clinicopathological parameters of colorectal adenocarcinomas.Methods:Immunohistochemical analysis of fascin-1 was performed in tissue microarrays of 91 surgical specimens, including 32 well, 33 moderately, and 26 poorly differentiated colorectal adenocarcinomas; and in 22 specimens from colorectal adenomas with dysplasia.Results:Scattered fascin-1 expression was demonstrated in 9 control specimens of normal colonic glandular epithelia. Higher fascin-1 immunostaining scores were significantly associated with advanced dysplasia in colorectal adenomas (mild 4.2 ± 1.3, moderate 13.5 ± 5.3, and severe 22.5 ± 6.7) and high-grade histopathological differentiation of colorectal adenocarcinomas (grade I 88.6 ± 9, grade II 101 ± 11, and grade III 144 ± 13). Higher immunostaining scores of fascin-1 were also significantly associated with advanced T stage (T1: 42 ± 10, T2: 60 ± 12, T3: 108 ± 12, and T4: 142 ± 15). Higher fascin-1 scores were related with more advanced M and N stages of colorectal carcinomas, but not significant correlation.Conclusions:Higher expression of fascin-1 correlates significantly with tumor grades and TNM stages in colorectal adenocarcinomas and also with levels of dysplastic change in colorectal adenomas.

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C-erbB-2 Oncoprotein in Gastric Carcinoma: Correlation with Clinical Stage and Prognosis

The International Journal of Biological Markers ◽

10.1177/172460080101600405 ◽

2001 ◽

Vol 16 (4) ◽

pp. 250-254 ◽

Cited By ~ 12

Author(s):

C.T.F. Oshima ◽

V. Pereira Lanzoni ◽

K. Iriya ◽

N.M. Forones

Keyword(s):

Clinical Stage ◽

Survival Rates ◽

Tumor Grade ◽

Positive Staining ◽

Gastric Adenocarcinomas ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Positive Immunostaining ◽

Poorly Differentiated ◽

Well Differentiated

The aim of this study was to investigate the expression of the oncogene c-erbB-2 in gastric tumors. Immunohistochemical study of the expression of c-erbB-2 was performed in formalin-fixed, paraffin-embedded sections from 82 gastric adenocarcinomas using polyclonal antibody. c-erbB-2-positive immunostaining was observed in 37 (45%) tumors. Positive staining was detected in 63% of well differentiated, 46% of moderately differentiated and 80% of papillary adenocarcinomas. In poorly differentiated adenocarcinomas, positivity for c-erbB-2 was observed in 21%. According to the Lauren classification, a higher frequency of c-erbB-2 positive staining was observed in intestinal type tumors (70%). During the follow-up period 43% of the patients with c-erbB-2 oncoprotein-negative tumors and 45% of the patients with c-erbB-2 oncoprotein-positive tumors died. There was no significant association between c-erbB-2 staining and sex, age, clinical stage, tumor grade, histological type or survival rates. In conclusion, almost half of the gastric cancers were positive for c-erbB-2. Nonetheless, the expression of c-erbB-2 oncoprotein did not play a role in prognosis.

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HER2 OVEREXPRESSION IN ENDOSCOPIC BIOPSY SAMPLE OF GASTRIC ADENOCARCINOMA BY IMMUNOHISTOCHEMISTRY

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2012.5.14 ◽

2012 ◽

pp. 109-118

Author(s):

Viet Nho Le ◽

Van Huy Tran ◽

Cong Thuan Dang ◽

Van To Ta

Keyword(s):

Gastric Adenocarcinoma ◽

Undifferentiated Carcinoma ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Endoscopic Biopsy ◽

Her2 Overexpression ◽

Tubular Adenocarcinoma ◽

Signet Ring ◽

Poorly Differentiated ◽

Well Differentiated

Background and aim: HER2 overexpression by immunohistochemistry is a prognostic maker in gastric cancer and helps to select candidates benefitted from targeted therapy with trastuzumab. This study is aimed at the assessing HER2 overexpression and its relationship with endoscopic and histopathological findings of gastric adenocarcinoma. Objectives and methods: Biopsy samples from 92 gastric cancer patients were examined for HER2 status by immunohistochemical staining. Results: 6.5% of tumors were cardia tumors and 93.5% were non-cardia tumors. Using the Lauren classification, 51.1% were intestinal type and 48.9% were diffuse type. Using WHO classification, 54.3% were tubular adenocarcinoma, 7.6% were mucinous adenocarcinoma, 15.2% were signet-ring cell carcinoma, and 22.8% were undifferentiated carcinoma. 32.6% were well-differentiated, 15.2% were moderately-differentiated, and 52.2% were poorly-differentiated carcinoma. HER2 was positive in 20.7% of gastric carcinomas, 50% cardia tumors and 18.6% non-cardia tumors. HER2 positivity among polypoid, fungating, ulcerated, and infiltrative types were 38.5%, 29.7%, 9.1% and 0%, respectively. HER2 overexpression in intestinal type was higher than that in diffuse type (31.9% vs. 8.9%, p = 0.009). HER2 overexpression in tubular adenocarcinoma, mucinous adenocarcinoma, signet-ring cell carcinoma, and undifferentiated carcinoma was 28.0%, 14.3%, 7.1% and 14.3%, respectively. HER2 overexpressions were different between differentiation degrees: 30% of well-differentiated tumors, 35.7% moderately-differentiated tumors, and 10.4% of poorly-differentiated tumors (p = 0.037). Conclusions: HER2 overexpression was found in 20.7% of endoscopic biopsy sample of gastric adenocarcinoma and was associated with endoscopic gross characteristic, Lauren histologic type and differentiation degree.

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Factors affecting overall survival in ductal adenocarcinoma of the pancreatic head. Experience of one center

Malignant tumours ◽

10.18027/2224-5057-2021-11-1-20-28 ◽

2021 ◽

Vol 11 (1) ◽

pp. 20-28

Author(s):

D. M. Kuchin ◽

Ya. I. Kolesnik ◽

H. G. Torgomyan ◽

V. E. Zagainov

Keyword(s):

Overall Survival ◽

Adjuvant Chemotherapy ◽

Vascular Invasion ◽

Survival Rates ◽

Pancreatic Head ◽

Ductal Adenocarcinoma ◽

Factors Affecting ◽

Poorly Differentiated ◽

Well Differentiated ◽

Major Factors

Purpose. To identify major factors affecting the overall survival (OS). To select the cohort of patients with the best prognosis.Materials and methods. A retrospective analysis included data of 268 patients, 128 men and 140 women, with median age of 59±10,53 (30 to 83) years. For multivariate analysis of survival, patients were selected who underwent pancreaticoduodenectomy (PD) for ductal adenocarcinoma of the pancreatic head.Results. Our study demonstrated that histologically verified vascular invasion (detected only in 30 % of patients who underwent PD with resection of the major vessels) statistically significantly affected the OS. The increased CA19-9 level over 500 U / L (detected in 32,3 % of cases) is the factor that significantly worsens the OS. Patients with high grade adenocarcinoma have significantly better survival rates compared with patients who have moderately or poorly differentiated adenocarcinoma (p = 0.014; median 26 months, 95 % CI 4.4–47.6 versus median 17 months, 95 % CI 15–19, an median: 13 months, 95 % CI 5–21, respectively). Also, the use of adjuvant chemotherapy has a positive effect on long-term outcomes (p = 0.0001; median 26 months, 95 % CI 21.7–30.3 versus median 13 months, 95 % CI 11.3–14.7).Conclusion. A well-differentiated tumor and the use of adjuvant chemotherapy significantly increase the OS of patients. Poorly differentiated tumor, CA19-9 level over 500 U / mL and the histologically confirmed vascular invasion significantly worsen the prognosis of these patients.

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Higher Expression of Epidermal Growth Factor Receptor Is Associated with Extracellular Matrix Metalloprotease Inducer in Colorectal Adenocarcinoma: Tissue Microarray Analysis of Immunostaining Score with Clinicopathological Parameters

Disease Markers ◽

10.1155/2006/890810 ◽

2006 ◽

Vol 22 (5-6) ◽

pp. 309-316 ◽

Cited By ~ 12

Author(s):

Jong-Shiaw Jin ◽

Chi-Ying Wu ◽

Yeh-Feng Lin ◽

Jia-Yi Wang ◽

Cheng-Ping Yu ◽

...

Keyword(s):

Colorectal Adenocarcinoma ◽

Growth Factor Receptor ◽

Clinicopathological Parameters ◽

Colorectal Cancers ◽

Matrix Metalloprotease ◽

Egfr Expression ◽

Poorly Differentiated ◽

Epidermal Growth ◽

Well Differentiated ◽

Colorectal Adenocarcinomas

Aim: Extracellular matrix metalloprotease inducer (EMMPRIN) expression was demonstrated in several cancers, but its expression profile in colorectal cancers remains unclear. Epidermal growth factor receptor (EGFR) was reported to regulate EMMPRIN expression in human epithelial cancers. Our purpose was to determine EMMPRIN expression and its relationship with EGFR in colorectal cancers.Methods: Immunohistochemical analysis of EMMPRIN and EGFR was performed in tissue microarray slides of 90 surgical specimens including 32 well differentiated, 35 moderately differentiated, and 23 poorly differentiated colorectal adenocarcinomas.Results: All colorectal adenocarcinomas showed significant immunohistochemical expression of EMMPRIN. The EMMPRIN scores in poorly differentiated (303 ± 21) and moderately differentiated (326 ± 17) colorectal adenocarcinoma were significantly higher than in well differentiated (166 ± 20) colorectal adenocarcinoma. EGFR expression was mainly on the cell surface of tumor cells and the immunostaining scores of EGFR were significantly associated with the advanced clinical T and N stages. A significantly positive relationship between EMMPRIN and EGFR immunostaining scores was also noted.Conclusions: Increased expression of EMMPRIN and EGFR in colorectal adenocarcinomas is associated with clinicopathological parameters of advanced colorectal adenocarcinoma stages.In addition, the data from this study support the notion that EGFR expression may up-regulate EMMPRIN expression.

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CT differentiation of poorly-differentiated gastric neuroendocrine tumours from well-differentiated neuroendocrine tumours and gastric adenocarcinomas

European Radiology ◽

10.1007/s00330-015-3600-z ◽

2015 ◽

Vol 25 (7) ◽

pp. 1946-1957 ◽

Cited By ~ 7

Author(s):

Seong Ho Kim ◽

Se Hyung Kim ◽

Min-A Kim ◽

Cheong-il Shin ◽

Joon Koo Han ◽

...

Keyword(s):

Neuroendocrine Tumours ◽

Gastric Adenocarcinomas ◽

Poorly Differentiated ◽

Well Differentiated

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Overexpression of UDP-Glucose 4-Epimerase Is Associated with Differentiation Grade of Gastric Cancer

Disease Markers ◽

10.1155/2019/6325326 ◽

2019 ◽

Vol 2019 ◽

pp. 1-5

Author(s):

Maria de Fátima Deodato de Souza ◽

Antônio Felix da Silva Filho ◽

Amanda Pinheiro de Barros Albuquerque ◽

Michael Williams Leal Quirino ◽

Mário Sérgio de Souza Albuquerque ◽

...

Keyword(s):

Gastric Cancer ◽

Gastric Adenocarcinoma ◽

Validation Cohort ◽

Histological Grade ◽

Cohort Analysis ◽

Tissue Expression ◽

Positive Staining ◽

Gastric Adenocarcinomas ◽

Well Differentiated ◽

Differential Tissue

The UDP-glucose 4-epimerase (GALE) is a glycosyltransferase, which acts on protein and lipid glycosylation in normal and neoplastic cells. This study is aimed at investigating the differential tissue expression of GALE and its possible association with clinical-pathological parameters and the outcome of gastric adenocarcinoma patients. Seventy-one patients were evaluated in relation to GALE expression by immunohistochemistry. Our results showed that 48 (67.6%) patients were GALE positive and 23 (32.4%) negative. Positive staining was present on well-differentiated and moderate-differentiated histological grade of gastric adenocarcinomas (p<0.0001). There was no significant association with outcome parameters (p>0.05). Besides that, our results corroborated with the validation cohort analysis, where the expression of GALE mRNA was also associated with the histological grade (p<0.001). These results suggest a possible use of this enzyme as a biomarker for well and moderately differentiated tumors.

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HER2 in gastric adenocarcinoma: where do we stand today?

Personalized Medicine ◽

10.2217/pme-2021-0004 ◽

2021 ◽

Author(s):

Khalil El Gharib ◽

Makram Khoury ◽

Hampig Raphael Kourie

Keyword(s):

Gastric Cancer ◽

Gastric Adenocarcinoma ◽

Survival Rates ◽

Metastatic Gastric Cancer ◽

Systematic Search ◽

Google Scholar ◽

Efficacy And Safety ◽

Pivotal Trial ◽

Gastric Adenocarcinomas

Aim: HER2 is a proto-oncogene expressed in 10–30% of gastric adenocarcinomas and is an ideal target for inhibition in malignancy with high recurrence and dismal survival rates. Materials & methods: A systematic search was conducted via PubMed, Google Scholar and the clinicaltrials.gov database to report the results of ongoing and past studies investigating HER2- inhibitors in gastric cancer. Results: Twenty-five studies were included; ToGA trial is the pivotal trial approving the use of trastuzumab in metastatic gastric cancer, followed by more studies investigating other HER2- inhibitors in this setting, as well as in local and locoregional malignancy. Conclusion: Anti-HER2 molecules are proving efficacy and safety in gastric cancer; the evidence is growing and association with other cancer agents is under investigation.

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