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

2009 ◽  
Vol 26 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Ying-Yu Lee ◽  
Cheng-Ping Yu ◽  
Chih-Kung Lin ◽  
Shin Nieh ◽  
Kuo-Feng Hsu ◽  
...  

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.

2007 ◽  
Vol 23 (3) ◽  
pp. 153-160 ◽  
Author(s):  
Wen-Chiuan Tsai ◽  
You-Chen Chao ◽  
Lai-Fa Sheu ◽  
Junn-Liang Chang ◽  
Shin Nieh ◽  
...  

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.


2007 ◽  
Vol 55 (9) ◽  
pp. 955-962 ◽  
Author(s):  
Wen-Chiuan Tsai ◽  
Jong-Shiaw Jin ◽  
Wei-Kuo Chang ◽  
De-Chuan Chan ◽  
Ming-Kung Yeh ◽  
...  

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.


2006 ◽  
Vol 22 (5-6) ◽  
pp. 309-316 ◽  
Author(s):  
Jong-Shiaw Jin ◽  
Chi-Ying Wu ◽  
Yeh-Feng Lin ◽  
Jia-Yi Wang ◽  
Cheng-Ping Yu ◽  
...  

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.


2021 ◽  
Author(s):  
Ingrid Espinoza ◽  
Sumit Agarwal ◽  
Marcelo Sakiyama ◽  
Veena Shenoy ◽  
W. Shannon Orr ◽  
...  

Abstract Background: The major histocompatibility complex class I polypeptide-related sequence A gene (MICA) is one of the ligands of NKG2D activating receptor. MICA stimulates NKG2D that further triggers activation of natural killer cells which leads to killing of infected target cells. Tumor cells utilize escape strategies to subvert the biological function of NKG2D by shedding overexpressing MICA. In this study, we determine the levels of MICA colorectal cancers (CRCs). Additionally, we establish correlations between MICA expression and clinical characteristics. Publicly available data and bioinformatics tools are used for validation purposes.Methods: We determined the MICA RNA expression levels and correlation with clinicopathological parameters in CRC using UALCAN web-portal. We performed immunohistochemical analysis on tissue microarrays having 192 samples, acquired from 96 CRC patients to validate the expression of MICA in CRC and adjacent uninvolved tissue and investigated its prognostic significance by Kaplan-Meir and proportional hazards methods.Results: Bioinformatics and immunohistochemical analyses showed that MICA expression was significantly upregulated in CRCs as compared to uninvolved and the overexpression of MICA was independent of pathologic stage, histotype, nodal metastasis status, p53-status, as well as patient’s race, age and gender. Moreover, PROGgeneV2 survival analysis of two cohorts showed poor prognosis of CRC patients exhibiting high MICA expression.Conclusions: Overall, our findings demonstrate high expression of MICA, suggest poor prognosis of CRC patients exhibiting high MICA expression. These results can be further explored due to its potential to provide clues to the mechanistic contributing role of the tumor microenvironment to the progression of progression of CRC.


2017 ◽  
Vol 141 (10) ◽  
pp. 1402-1412 ◽  
Author(s):  
Megan L. Troxell ◽  
Thomas Long ◽  
Jason L. Hornick ◽  
Abiy B. Ambaye ◽  
Kristin C. Jensen

Context.— Immunohistochemical analysis of estrogen receptor (ER) and progesterone receptor (PgR) expression in breast cancer is the current standard of care and directly determines therapy. In 2010 the American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) published guidelines for ER and PgR predictive testing, encompassing preanalytic, analytic, postanalytic factors; antibody validation; and proficiency testing. Objective.— To compare the performance of different antibody reagents for ER and PgR immunohistochemical analysis by using CAP proficiency testing data. Design.— The CAP PM2 survey uses tissue microarrays of ten 2-mm cores per slide. We analyzed survey data from 80 ER and 80 PgR cores by antibody clone from more than 1200 laboratories. Results.— Laboratories used the ER antibodies SP1 (72%), 6F11 (17%), 1D5 (3%), and the PgR antibodies 1E2 (61%), 16 (12%), PgR-636 (13%), PgR-1294 (8%) in 2015. While 63 of 80 ER cores (79%) were scored similarly using each of the 3 antibodies, there were significant differences for others, with SP1 yielding more positive interpretations. Four cores were scored as ER negative by more than half of the laboratories using 1D5 or 6F11, while SP1 produced positive results in more than 70% of laboratories using that antibody. Despite the greater variety of PgR antibody reagents and greater PgR tumor heterogeneity, 61 of 80 cores (76%) were scored similarly across the 4 PgR antibodies. Conclusions.— Accurate ER and PgR testing in breast cancer is crucial for appropriate treatment. The CAP proficiency testing data demonstrate differences in staining results by ER clone, with SP1 yielding more positive results.


2005 ◽  
Vol 129 (9) ◽  
pp. 1100-1105 ◽  
Author(s):  
Lindsey B. De Lott ◽  
Carl Morrison ◽  
Saul Suster ◽  
David E. Cohn ◽  
Wendy L. Frankel

Abstract Context.—CDX2, a critical nuclear transcription factor for intestinal development, is expressed in intestinal epithelium and adenocarcinomas. Objectives.—To determine if CDX2 is a useful marker for intestinal-type differentiation and to correlate tumor histology with CDX2 staining in colorectal adenocarcinomas. Design.—Tissue microarrays from 71 colorectal adenocarcinomas, 31 hepatocellular carcinomas, 47 lung adenocarcinomas, 55 squamous cell carcinomas of the lung, 69 neuroendocrine carcinomas of the lung and 43 of the pancreas, 57 pancreatic adenocarcinomas, and 256 endometrial adenocarcinomas were stained with antibody against CDX2. Results.—CDX2 staining was positive in 51 (71.8%) of 71 colorectal cancers, including 38 (74.5%) of 51 well- or moderately differentiated tumors and 13 (65.0%) of 20 high-grade tumors. Of the high-grade tumors, 5 (71.4%) of 7 mucinous, 3 (100%) of 3 signet ring cell, and 5 (50.0%) of 10 poorly differentiated tumors were positive. Other tumors showing occasional CDX2 staining included 1 of 30 well- or moderately differentiated neuroendocrine carcinomas of the lung and 2 of 43 from the pancreas, 1 of 47 lung adenocarcinomas, 3 of 57 pancreatic adenocarcinomas, and 15 of 256 endometrial carcinomas. Hepatocellular, poorly differentiated neuroendocrine carcinoma of the lung and squamous cell carcinomas of the lung were not immunoreactive for CDX2. Conclusions.—CDX2 is a useful marker for intestinal-type differentiation, is rarely seen in tumors from the other sites evaluated, and may be useful in determining the site of origin for some metastatic tumors. However, CDX2 is not a sensitive marker for poorly differentiated colorectal carcinoma.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Agnieszka Halon ◽  
Piotr Donizy ◽  
Przemyslaw Biecek ◽  
Julia Rudno-Rudzinska ◽  
Wojciech Kielan ◽  
...  

The role of HER-2 expression as a prognostic factor in gastric cancer (GC) is still controversial. The aim of the study was to asses HER-2 status, its correlations with clinicopathological parameters, and prognostic impact in GC patients. Tumor samples were collected from 78 patients who had undergone curative surgery. In order to evaluate the intensity of immunohistochemical (IHC) reactions two scales were applied: the immunoreactive score according to Remmele modified by the authors and standardised Hercep test score modified for GC by Hofmann et al. The HER-2 overexpression was detected by IHC in 23 (29.5%) tumors in Hercep test (score 2+/3+) and in 24 (30.7%) in IRS scale (IRS 4–12). The overexpression of HER-2 was associated with poorly differentiated tumors, but this correlation was not significant (P=0.064). No relationship was found between HER-2 expression and primary tumor size and degree of spread to regional lymph nodes. Both univariate and multivariate analyses revealed that TNM stage and patient’s age were the crucial negative prognostic factors. No correlation was observed between patient survival and expression of HER-2 estimated using both scales. This research did not confirm HER-2 expression (evaluated with immunohistochemistry) value as a prognostic tool in GC.


2008 ◽  
Vol 65 (11) ◽  
pp. 820-824
Author(s):  
Sladjana Zivkovic ◽  
Milos Kostov ◽  
Svetlana Pavlovic ◽  
Zaklina Mijovic

Background/Aim. Renal carcinoma represents histologically heterogeneous group of malignant tumors, with various clinical aggressiveness. The frequency of p53 mutation in primal renal carcinoma is rare, although there are information about its heterogeneous accumulation. The loss of protein p16 expression in primal renal carcinoma is detected in 20-30% of the cases. The aim of this paper was to determine frequency of mutated protein p53 and expression of protein p16INK4a in renal carcinoma, to analyze their correlative relation and relation with the examined clinicopathological parameters. Methods. The examination included 12 patients (66.7% men, 33.3% women), with patohistologically verified renal carcinoma. Expression of mutated form of protein p53 and protein p16 was determined in tissue samples, by immunohistochemical analysis using of mice monoclonical antibodies produced by DAKO, Denmark. Results. In 9 (75%) of the cases was detected mutated protein p53, of whom 66.6% had higher histological gradus of tumor (G3-4) and higher pathological stadium of the disease (pT3a-b) at the same time. In 7 (58.3%) and 5 (41.7%) of the cases expression of protein p16, the loss of expression of protein p16 were detected respectively. A statistically significant positive correlation was determined between pathological stadium of disease (TNM) and the degree of tumor differentiation (G) (? = 0.834; p < 0.001), as well as between TNM and mitotic index (? = 0.622; p = 0.031). Conclusion. A mutated form of protein p53 exists in 75% of the cases with the renal carcinoma and 66.6% of then have higher histological gradus of tumor and higher stadium of tumor disease at the same time. Coexpression of mutated protein p53 and protein p16INK4a in renal carcinoma is not statistically significant and it is not in correlation with clinicopathological parameters. Immunohistochemical analysis of mutated protein p53 in renal carcinoma can have predictive significance.


2021 ◽  
Vol 21 ◽  
Author(s):  
Antonio Ieni ◽  
Cristina Pizzimenti ◽  
Giuseppe Giuffrè ◽  
Rosario Alberto Caruso ◽  
Giovanni Tuccari

Background: The immunohistochemical analysis of autophagy-related proteins (ATGs) has been recently applied in human pathology to study differentiation and cancer progression. The aim of the present study is to analyze a cohort of gastric carcinomas (GC) by five ATG antisera (Beclin-1, LC3A/B, p62, ULK-1 and AMBRA-1), also evaluating their possible relationship with clinicopathological parameters, HER2 status and final outcome of patients. Methods: A cohort of 123 GCs has been studied by ATG antisera utilizing Masuda's criteria that define positive cases in which at least two out of five protein expressions were documented. Results: The immunohistochemical signature for autophagy (A-IHC) was 49.59% as a whole. The percentage of A-IHC ranged from 31% for poorly cohesive carcinomas to 56% for adenocarcinomas. The performance of each ATG immunomarker documented high values for sensitivity, specificity and efficiency for LC3A/B, Beclin-1 and p62. In univariate analysis of GC, grade, stage, Ki67 expression, HER2 status as well as A-IHC appeared as emerged as relevant parameters with a high p-value (p < 0.001). Finally, in multivariate analysis, HER2 status, stage and A-IHC emerged as independent prognostic variables. In the comparison of survival curves, GC cases immunoreactive for A-IHC exhibited a shorter survival with a worse outcome. Conclusions: We have hypothesized that A-IHC could represent an additional morphological tool to provide prognostic elements in order to identify patients affected by aggressive with shorter survival and worse outcome.


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