Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer

2014 ◽  
Vol 395 (9) ◽  
pp. 1087-1093 ◽  
Author(s):  
David L. Kolin ◽  
Keiyan Sy ◽  
Fabio Rotondo ◽  
Mena N. Bassily ◽  
Kalman Kovacs ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tissue Microarray ◽  
Human Tissue ◽  
Serine Proteases ◽  
Prognostic Significance ◽  
Staining Intensity ◽  
Clinicopathological Parameters ◽  
Tissue Kallikrein ◽  
Advanced Stage ◽  
Stage Disease

Abstract The prognosis of patients following surgery for gastric cancer is often poor and is estimated using traditional clinicopathological parameters, which can be inaccurate predictors of future survival. Kallikreins are a group of serine proteases, which are differentially expressed in many human tumors and are being investigated as potential cancer biomarkers. This study assessed the prognostic utility of human tissue kallikrein-like peptidases 6 and 10 (KLK6 and KLK10) and correlated their expression with histopathological and clinical parameters in gastric cancer. We constructed a gastric tumor tissue microarray from 113 gastrectomy specimens and quantified KLK6 and KLK10 expression using immunohistochemistry. To overcome the problem of inter-observer variability and subjectivity in immunohistochemistry interpretation, a whole-slide scanned image of the tissue microarray was analyzed using an automated algorithm to quantify staining intensity. KLK6 expression was positively correlated with nodal involvement (p=0.002) and was predictive of advanced-stage disease (p<0.05). Kaplan-Meier survival curves revealed that tumors expressing high levels of KLK6 were significantly associated with significantly lower overall survival (p=0.04). KLK10 overexpression was also a predictor of advanced-stage disease (p<0.01), but was not significantly correlated with lymph node involvement or survival period. Our results show the potential ability of KLK6 as a prognostic marker for gastric cancer.

Prognostic significance of human tissue kallikrein-related peptidases 11 and 15 in gastric cancer

Tumor Biology ◽  
2015 ◽  
Vol 37 (1) ◽  
pp. 437-446 ◽  
Author(s):  
David L. Kolin ◽  
Keiyan Sy ◽  
Fabio Rotondo ◽  
Mena N. Bassily ◽  
Kalman Kovacs ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Human Tissue ◽  
Prognostic Significance ◽  
Tissue Kallikrein

Clinical significance of kallikrein-related peptidase 7 (KLK7) in colorectal cancer

2009 ◽  
Vol 101 (04) ◽  
pp. 741-747 ◽  
Author(s):  
Konstantina Mathioudaki ◽  
Panagiotis Prezas ◽  
Dimitra Alexopoulou ◽  
Eleftherios Diamandis ◽  
Dimitris Xynopoulos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Stratum Corneum ◽  
Human Tissue ◽  
Serine Proteases ◽  
Human Cancer ◽  
Disease Free Survival ◽  
Normal Colonic Mucosa ◽  
Tissue Kallikrein ◽  
Human Cancer Cell Lines

SummaryHuman tissue kallikrein-related peptidases are a family of 15 secreted serine proteases, located at chromosome 19q13.4. Most of them have been reported to be potential biomarkers for several carcinomas and other diseases. Human tissue kallikrein-related peptidase 7 (KLK7) has been purified from human stratum corneum and resembles a chymotryptic endopeptidase originally called stratum corneum chymotryptic enzyme (SCCE). In this study, we examined for the first time, the prognostic value of KLK7 mRNA expression, using a semi-quantitative RT-PCR method, in 105 colorectal cancer tissues for 54 of which, paired normal colonic mucosa were available. Furthermore, we analysed the expression of KLK7 in 10 adenomas, in 18 biopsies of inflamed colon mucosa, as well as in 22 human cancer cell lines of various origin, four of them being of colon. A defined number of colon cancer samples were also examined by immunohisto-chemistry. KLK7 expression was higher in cancerous than in normal tissues. Less differentiated tumors of more advanced stage showed higher KLK7 expression. Follow-up analysis revealed that KLK7 was significantly associated with shorter overall survival (OS) and disease-free survival (DFS). In addition, selected colon cancer samples highly expressing KLK7 gene, showed intense immunohistochemical staining for KLK7, enhancing RTPCR results. Present data suggest that KLK7 gene is up-regulated in colon cancer and its expression predicts poor prognosis for colon cancer patients.

scholarly journals HER-2 Expression in Immunohistochemistry Has No Prognostic Significance in Gastric Cancer Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Agnieszka Halon ◽  
Piotr Donizy ◽  
Przemyslaw Biecek ◽  
Julia Rudno-Rudzinska ◽  
Wojciech Kielan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Test Score ◽  
Prognostic Significance ◽  
Clinicopathological Parameters ◽  
Prognostic Impact ◽  
Curative Surgery ◽  
Regional Lymph Nodes ◽  
Poorly Differentiated ◽  
Her 2 ◽  
Gastric Cancer Patients

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.

Prognostic Significance of Tissue-Type Plasminogen Activator (tPA) Content in Gastric Cancer and Surrounding Mucosa

2002 ◽  
Vol 17 (3) ◽  
pp. 169-176 ◽  
Author(s):  
L. Sanz ◽  
F. Vizoso ◽  
P. Vérez ◽  
M.T. Allende ◽  
M.G. Corte ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Solid Phase ◽  
Prognostic Significance ◽  
Tissue Type ◽  
Gastric Neoplasms ◽  
Clinicopathological Parameters ◽  
Adjacent Mucosa ◽  
Type Plasminogen Activator ◽  
Wide Variability ◽  
Gastric Cancer Patients

Aims We analyzed the tPA content in primary gastric carcinomas and surrounding mucosa in order to assess the relationship between tPA content, clinicopathological tumor characteristics, and estrogen and progesterone receptor content. We evaluated the prognostic value of this serine protease in gastric cancer patients. Patients and methods 122 resected gastric neoplasms and 95 adjacent mucosa samples were studied. The tPA content was measured in cytosol by an ELISA method. Cytosolic ER and PgR were measured with a solid phase enzyme immunoassay. Results Cytosolic tPA levels in neoplastic tissues (median 1.0 ng/mg prot) were significantly lower (p=0.002) than those found in paired mucosa samples (median 2.3 ng/mg prot). There was no significant association between tPA levels and clinicopathological parameters or PgR content, but tPA levels were significantly correlated with ER content. The intermediate-tPA-content group, corresponding to samples with between 0.3 and 1.70 ng/mg protein, proved to have a significantly high risk of relapse. Conclusions We found a wide variability in tPA levels in gastric carcinoma and adjacent mucosa samples, with significantly decreased levels in tumors and a significantly positive relationship between tPA levels and ER status. There was a non-monotonic relationship between tPA levels and prognosis in patients with gastric cancer.

Evaluation and prognostic significance of human tissue kallikrein-related peptidase 10 (KLK10) in colorectal cancer

Tumor Biology ◽  
2012 ◽  
Vol 33 (4) ◽  
pp. 1209-1214 ◽  
Author(s):  
Constantina Petraki ◽  
Youssef M. Youssef ◽  
William Dubinski ◽  
Zsuzsanna Lichner ◽  
Andreas Scorilas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Human Tissue ◽  
Prognostic Significance ◽  
Tissue Kallikrein

scholarly journals KK-LC-1 may be an effective prognostic biomarker for gastric cancer

2020 ◽  
Author(s):  
Jun Ji ◽  
Jiahui Chen ◽  
Anqiang Wang ◽  
Wei Zhang ◽  
Hongge Ju ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Staining Intensity ◽  
Good Prognosis ◽  
Clinicopathological Parameters ◽  
Chi Square ◽  
Clinical Prognosis ◽  
Cox Regression Analysis ◽  
Normal Tissues

Abstract Background: To detect the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in gastric cancer (GC) specimens and analyze the associations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis. Methods: A total of 94 patients with GC who underwent surgical resection were enrolled in this study. The expression of KK-LC-1 in GC tissues was detected by immunohistochemistry. The assessment of KK-LC-1 expression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of KK-LC-1 in the cytoplasm and was scored to achieve respective H-score values. The correlations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox regression. Results: In the cytoplasm, the expression of KK-LC-1 in tumor tissues was significantly higher than that in normal tissues (P < 0.001, respectively). Using the median H-score as the cutoff value, it was discovered that, GC patients with higher levels of KK-LC-1expression in the cytoplasm, had favorable overall survival (P =0.016), and it was still statistically meaningful in Cox regression analysis. At the same time, the study found that there was a negative correlation between KK-LC-1’s protein expression and the pathological grade of the tumor (P = 0.036). Conclusions: Our research data shows that KK-LC-1’s expression in GC is higher than that of normal tissues, which is associated with a longer overall survival in GC. KK-LC-1 can be used as a biomarker for GC patients with good prognosis.

scholarly journals The prognostic significance of macroscopic serosal change in subserosal invasion (stage T3) gastric cancer

2019 ◽  
Vol 101 (4) ◽  
pp. 249-255 ◽  
Author(s):  
B Zhao ◽  
D Mei ◽  
J Zhang ◽  
S Zou ◽  
Hn Lu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumour Size ◽  
Prognostic Significance ◽  
Advanced Stage ◽  
Tumour Invasion ◽  
Curative Gastrectomy ◽  
Serosal Surface ◽  
Invasion Stage ◽  
Pathological Evaluation ◽  
Unfavourable Prognosis

Background For patients with gastric cancer intraoperative macroscopic serosal change is not always consistent with pathological T stage. We investigated whether macroscopic serosal change is associated with unfavourable prognosis of patients with gastric cancer. Methods We reviewed 856 patients with stage T3 gastric cancer who underwent curative gastrectomy in our institution. All patients were classified as serosa negative and serosa positive according to the macroscopic serosal change during the operation. The prognostic difference between two groups was compared and clinicopathologic features were analysed. Results The percentage of macroscopic serosal change accounted for 55.7% of all patients. Compared with normal serosal surface, the patients with macroscopic serosal change had larger tumour size, more extensive stomach involvement and more advanced stage N. The prognosis of stage T3 with macroscopic serosal change was significantly poorer than that of those with normal serosal surface, especially for those with stages T3N0 and T3N1. Multivariate analysis identified macroscopic serosal change as an independent factor associated with unfavourable prognosis of stage T3 cancer. Conclusion Although the depth of tumour invasion mainly depends on pathological evaluation after surgery, the prognostic significance of intraoperative macroscopic serosal change should not be ignored for those patients with subserosal invasion.

Clinicopathological and Prognostic Significance of Platelet-Lymphocyte Ratio (PLR) in Gastric Cancer: A Meta-Analysis

2019 ◽  
Author(s):  
Xunlei Zhang ◽  
Wenjing Zhao ◽  
Yang Yu ◽  
Xue Qi ◽  
Li Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Cochrane Library ◽  
Clinicopathological Parameters ◽  
Poor Overall Survival ◽  
Lymphocyte Ratio ◽  
Platelet Lymphocyte Ratio ◽  
Inflammatory Parameters

Abstract Background: Systemic inflammatory parameters, such as the elevator PLR (platelet-lymphocyte ratio), have been found to be associated with the prognosis in gastric cancer (GC); however, the results remain controversial. So we aimed to evaluate the prognostic role of the PLR in gastric cancer by conducting this meta-analysis. Methods: We performed a systematic literature search in PubMed, Embase and the Cochrane Library. The hazard ratio (HR) /Odds Ratio (OR) and its 95% confidence (CI) of survival outcomes and clinicopathological parameters were calculated. Results: A total of 38 studies (39 cohorts) with 23,317 GC patients were included in the final meta-analysis. The pooled results showed that elevated PLR was significantly associated with poor overall survival (OS) (HR: 1.37, 95% CI: 1.25-1.51, p < 0.001; I2= 82.10%, Ph < 0.001) and disease-free survival (DFS) (HR 1.52, 95%CI 1.22–1.90, P< 0.001, I2= 88.6%, Ph< 0.001) of GC patients. Furthermore, patients with elevated PLR had a higher risk of lymph node metastasis (OR = 1.33, 95% CI: 1.03–1.70, p=0.027), serosal invasion (T3 +T4) (OR = 1.58, 95% CI: 1.09–1.31, p=0.017) and increased advanced stage (III+IV) (OR = 1.37, 95% CI: 1.00–1.89, p=0.050). Conclusions: This meta-analysis demonstrated that elevated PLR was a prognostic factor for poor OS and DFS, and associated with clinicopathological parameters in patients with GC.

Correlation between Intratumoral Cellular Microenvironment, Clinicopathological Parameters and Prognosis in Hodgkin Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2273-2273
Author(s):  
Peter Kamper ◽  
Anne-Sofie Hammer ◽  
Stephen Hamilton-Dutoit ◽  
Knud Bendix ◽  
Bent Honoré ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Hodgkin Lymphoma ◽  
Clinicopathological Parameters ◽  
Advanced Stage ◽  
Histological Subtypes ◽  
Cellular Microenvironment ◽  
Neoplastic Cells ◽  
Stage Disease ◽  
Cell Expression

Abstract Hodgkin lymphoma (HL) is characterized by a minority of neoplastic, Hodgkin, Reed-Sternberg (HRS) cells surrounded by a heterogeneous background of non-neoplastic cells. Previous studies have described a prognostic role of the cellular composition in HL. The aim of the present study was to correlate parameters related to the intratumoral cellular microenvironment with clinicopathological features and prognosis in a cohort of previously untreated HL patients. For this purpose a tissue microarray Array (TMA) consisting of pairs of representative cores (2mm) from each tissue specimen and from positive and negative controls was constructed. Immunohistochemical stains of cellular antigens were assessed and graded. Tissue samples and clinical record data from a total of 87 HL patients were analysed. Histological subtypes were distributed as follows: nodular sclerosis (NS)61 cases (71%), mixed cellularity (MC) 15 (17%), nodular lymphocyte- predominant (NLP) 9 (10%) and lymphocyte depleted 2 (2%). The median age was 36.7 yrs (range 5–83 yrs and the male to female ratio 1.6. 56 had localised (67%) 27 had advanced stage disease (32%). Anaemia and leukocytosis were present in 4 (5%) and 15 (17%) cases, respectively. All patients were treated according to standard guidelines (chemo- radiotherapy for localised disease and ABVD/COPP- based chemotherapy for advanced stage disease). Immunohistichemical stains were used to characterise and quantify the neoplastic and non-neoplastic cells within tumor lesions. Following antigens were studied: CD3, CD20, CD30, CD15, CD10, STAT-6, MUM-2, FAS, p53 and MIB-1. Among histological subtypes NLP HL was, as expected, the one most frequently displaying CD20 positivity, while CD15 and CD30 were more common in classical HL (cHL). A strong CD3 expression in the non-neoplastic by-stander population was inversely correlated with the presence of leukocytosis in the peripheral blood. An opposite pattern was found in cases, mostly cHL, with high expression of STAT-6 in the tumor cell population. In addition to leukocytosis STAT-6 expression also correlated to younger age (60 yrs or less) and presence of B-symptoms. Time-related endpoint analysis was restricted to NS, representing the largest subgroup (n=61). Interestingly, a significant adverse impact on overall survival (OS) was detected in cases with a strong tumor cell expression of STAT-6. Even more marked was the unfavorable prognostic value of low or lacking tumor cell expression of CD30 (p=0.0012) or by-stander cell expression of CD3 (p=0,0133). All these findings were far more evident in younger (≤ 60 yrs) NS-HL patients than in their elderly counterparts. These three parameters where not, or only minimally, influenced by classical clinical prognosticators such as clinical stage, B-symptoms or anemia. Moreover, the adverse prognostic influence of these factors was mutually increased in those cases, where they occurred in combination (high STAT6 + low CD30: p=0.0001; low CD30 + low CD3: p=0.0004; high STAT6 + low CD3: p=0.0017). The role of the STAT family of proteins and that of T-regulatory cells in the pathophysiology of HL should be further elucidated.

Membranous Levels of C-Erbb-2 Oncoprotein in Gastric Cancer: Their Relationship with Clinicopathological Parameters and Their Prognostic Significance

2004 ◽  
Vol 19 (4) ◽  
pp. 268-274 ◽  
Author(s):  
F.J. Vizoso ◽  
M.D. Corte ◽  
A. Alvarez ◽  
I. García ◽  
J.M. del Casar ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Clinicopathological Parameters ◽  
Clinical Value ◽  
Free Survival ◽  
Gastric Carcinomas ◽  
Novel Drug ◽  
Immunoenzymatic Assay

Background The protein encoded by the c-erbB-2 gene is a membrane receptor expressed in a variety of solid human cancers and directly related to poor prognosis. The objective of this work was to evaluate the clinical value of the quantification of membranous oncoprotein levels in gastric cancer. Materials and methods Membranous c-erbB-2 levels were examined by means of a sandwich immunoenzymatic assay in 82 patients with gastric cancer. The median follow-up period for these patients was 16 months. In addition, c-erbB-2 expression was analyzed by immunohistochemistry in 57 gastric carcinomas. Results Membranous c-erbB-2 levels ranged widely in the studied tumors (44–112,000 NHU/mg protein). Median c-erbB-2 content was significantly higher in intestinal-type tumors than in diffuse-type tumors (p=0.01). In addition, high levels of c-erbB-2 were significantly associated with shorter relapse-free survival and overall survival in patients with resectable gastric carcinomas (p=0.01 and p=0.04, respectively). However, the correlation between immunohistochemistry and ELISA determinations did not reach statistical significance. Conclusion Our results suggest a potential prognostic value of membranous c-erbB-2 quantification by immunoenzymatic assay in gastric cancer. However, its possible role in the selection of patients with a view to the possible introduction of Herceptin as a novel drug against gastric cancer is at present uncertain.

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