scholarly journals Relationship between S100A4 protein expression and pre-operative serum CA19.9 levels in pancreatic carcinoma and its prognostic significance

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Fuxin Jia ◽  
Mengmeng Liu ◽  
Xiao Li ◽  
Fen Zhang ◽  
Shuqiang Yue ◽  
...  

Abstract Background Pancreatic carcinoma (PC) is one of the most lethal malignancies, and its poor prognosis is strongly associated with invasion and metastasis. CA19.9 is considered to be the most sensitive serum marker for PC in clinical practice; however, the detection of CA19.9 in PC has a certain false positive and false negative rate. The expression of the calcium-binding protein S100A4 has been reported to be associated with poor prognosis in various cancers. This study aimed to investigate the relationship between S100A4 and CA19.9 and its prognostic significance in PC. Methods We performed immunohistochemical staining for S100A4 in formalin-fixed, paraffin-embedded blocks of 128 PC tissues. The levels of S100A4 expression and pre-operative serum CA19.9 were correlated with clinicopathological parameters. The possible correlation between S100A4 protein expression and pre-operative serum CA19.9 levels were evaluated using the chi-square test and Spearman correlation. Survival was assessed by Kaplan–Meier analysis together with a single variable or multivariate Cox analysis. Results A significant positive correlation between S100A4 expression and pre-operative serum CA19.9 level was observed in PC tissues (ρ = 0.202, P = 0.022). The co-expression of both proteins correlated significantly with tumor differentiation (ρ = − 0.280, P = 0.001), TNM stage (ρ = − 0.389, P = 0.000), and lymph node metastasis (ρ = 0.254, P = 0.008). Upregulation of S100A4 was identified as a significant, independent predictor of poor overall survival (P = 0.000). Moreover, higher serum CA19.9 levels (≥ 35 U/mL) were also recognized as an independent predictor of inferior overall survival (P = 0.001). Additionally, upregulation of S100A4 and higher pre-operative serum CA19.9 levels (≥ 35 U/mL) in patients with PC contributed to a significant decrease in overall survival (P = 0.000). Conclusions The expression levels of S100A4 in PC tissues were positively correlated with pre-operative serum CA19.9 levels. S100A4 expression and pre-operative serum CA19.9 levels were significant, independent prognostic factors for the overall survival of patients with PC. S100A4 expression/pre-operative serum CA19.9 levels may prove useful as dual prognostic biomarkers for PC. Analysis of CA19.9 in combination with S100A4 can better predict the prognosis of PC.

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 265-272 ◽  
Author(s):  
O Hermine ◽  
C Haioun ◽  
E Lepage ◽  
MF d'Agay ◽  
J Briere ◽  
...  

Abstract Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T- cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.


2018 ◽  
Vol 56 (3) ◽  
pp. 377-388 ◽  
Author(s):  
Bernadette Rogez ◽  
Quentin Pascal ◽  
Audrey Bobillier ◽  
François Machuron ◽  
Chann Lagadec ◽  
...  

CD44+/CD24– phenotype has been used to identify human and canine mammary cancer stem-like cells. In canine mammary tumors, CD44+/CD24– phenotype has been associated with high grade and lymph node infiltration. However, several studies have reported opposing results regarding the clinical significance of phenotypic groups formed by the combination of CD44 and CD24 in both human and canine mammary tumors. So far, no study has investigated the correlation between these phenotypes and survival in dogs. The aim of this study was to investigate the expression and distribution of CD44 and CD24 in canine mammary carcinomas and to correlate them with histological diagnosis and survival in a well-characterized cohort. Immunohistochemistry was performed in 96 mammary carcinomas with antibodies against CD44 and CD24. Expression of CD44+ and CD44+/CD24– phenotype was detected in 75 of 96 (78%) and 63 of 96 (65.6%) carcinomas, respectively. Their expression was associated with tumor type, occurring more often in tubular complex carcinomas than in solid carcinomas. CD44+/CD24– phenotype was associated with a better overall survival ( P = .001). CD24+ expression was detected in 52 of 96 tumors (54%) and CD44–/CD24+ phenotype in 39 of 96 tumors (40.6%). Both were associated with poor clinicopathological parameters (high grade, and emboli). No correlation with overall survival was observed. CD44+/CD24– expression was associated with a better prognosis and occurred at high frequency and high level, indicating that this phenotype is not suitable to detect cancer stem cells in canine mammary carcinomas. Although further studies are needed, our results suggest that CD24 may constitute a valuable marker of poor prognosis for canine mammary carcinomas.


Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 265-272 ◽  
Author(s):  
O Hermine ◽  
C Haioun ◽  
E Lepage ◽  
MF d'Agay ◽  
J Briere ◽  
...  

Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T- cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.


BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e037614
Author(s):  
Xin Chen ◽  
Jing Li ◽  
Xunlei Zhang ◽  
Yushan Liu ◽  
Jindong Wu ◽  
...  

ObjectiveOur study aimed to evaluate the prognostic and clinicopathological significance of pretreatment mean platelet volume (MPV) on cancer by using meta-analysis of published studies.DesignMeta-analysis.Data sourcesRelevant studies available before 22 December 2019 were identified by searching MEDLINE, EMBASE.Eligibility criteriaAll published studies that assessed the prognostic and clinicopathological significance of pretreatment MPV on cancer were included.Data extraction and synthesisStudies were identified and extracted by two reviewers independently. The HR/OR and its 95% CIs of survival outcomes and clinicopathological parameters were calculated.ResultsA total of 38 eligible studies (41 subsets) with 9894 patients with cancer were included in the final meta-analysis. MPV level was not significantly associated with both overall survival (HR 0.98, 95% CI 0.84 to 1.14) and disease-free survival (HR 1.22, 95% CI 0.86 to 1.73) of patients with cancer. Neither advanced nor mixed-stage tumour patients showed significant association between MPV and overall survival (HR 1.36, 95% CI 0.96 to 1.94, HR 0.90, 95% CI 0.74 to 1.09). However, high MPV had the strongest relationship with poor overall survival (HR 2.01; 95% CI 1.08 to 3.41) in gastric cancer, followed by pancreatic cancer (HR 1.54; 95% CI 1.31 to 1.82). Whereas in the subgroup using receiver operating characteristic curve method to define cut-off values, low MPV was significantly related to poor overall survival (HR 0.78, 95% CI 0.64 to 0.95). In addition, MPV had no significant association with age (OR 0.96, 95% CI 0.90 to 1.02), sex (OR 1.04, 95% CI 1.00 to 1.09), depth of cancer invasion (OR 0.90, 95% CI 0.77 to 1.04) and tumour stage (OR 0.91, 95% CI 0.78 to 1.07).ConclusionsPretreatment MPV level is of no clearly prognostic significance in cancers and no significant association with clinicopathological parameters of patients with cancers.


2001 ◽  
Vol 19 (4) ◽  
pp. 1118-1127 ◽  
Author(s):  
Hiroyuki Yamamoto ◽  
Fumio Itoh ◽  
Shouhei Iku ◽  
Yasushi Adachi ◽  
Hiroshi Fukushima ◽  
...  

PURPOSE: A disruption in the balance between the matrix metalloproteinases (MMPs) and their natural inhibitors, tissue inhibitors of metalloproteinases (TIMPs), has been implicated in the progression of many types of cancer. The aim of this study was to determine whether a specific MMP or TIMP has clinicopathologic and prognostic significance in pancreatic carcinoma. PATIENTS AND METHODS: Using immunohistochemistry, we analyzed 70 pancreatic ductal adenocarcinoma tissues for expression of MMP-1, MMP-2, MMP-3, MMP-7 (matrilysin), MMP-9, MT1-MMP, TIMP-1, and TIMP-2. The results were matched with clinicopathologic characteristics and patients’ survival. The effects of the suppression of a specific MMP on in vitro invasiveness of pancreatic carcinoma cells were also examined. RESULTS: Expression of MMP-1, MMP-2, MMP-3, matrilysin, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 was detected in either tumor cells or tumor stromal cells, or in both components, at varying frequencies. Among MMPs, matrilysin showed a unique distribution in the tumor nests; its expression was usually most pronounced at the invasive front of the tumors. Sections with immunostaining signals in more than 30% of carcinoma cells at the invasive front, which were observed in 40 cases (57%), were judged to be positive for matrilysin. Matrilysin positivity was significantly correlated with pT, pN, and pM categories and with more advanced pathologic tumor-node-metastasis stages. Patients with matrilysin-positive carcinoma had a significantly shorter overall survival time than did those with matrilysin-negative carcinoma. Matrilysin was a significant independent prognostic factor for overall survival in multivariate analysis. In contrast, there was no correlation between the presence of other MMPs or TIMPs and clinicopathologic characteristics, nor was the presence of individual MMPs or TIMPs related to survival. Antisense matrilysin-transfected CFPAC-1 cells expressed reduced levels of matrilysin and demonstrated a similar growth potential but were less invasive in vitro compared with neotransfected CFPAC-1 cells. CONCLUSION: Our results suggest that matrilysin may play a key role in progression of pancreatic carcinoma and thereby contribute to a poor prognosis. Because different synthetic MMP inhibitors affect different types of MMPs to a different degree, examination of the expression of MMPs, especially that of matrilysin, may serve as an indicator for selecting the most effective MMP inhibitor.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6060-6060 ◽  
Author(s):  
William S. Chen ◽  
Ranjit Bindra ◽  
Allen Mo ◽  
Thomas Hayman ◽  
Zain Husain ◽  
...  

6060 Background: HPV infection is associated with high p16 expression and relatively good prognosis in head and neck cancers. Analysis of CDKN2A, the gene that encodes the p16 tumor suppressor protein, may further elucidate the association between HPV status and prognosis in head and neck squamous cell carcinomas (HNSCCs). We aimed to identify whether CDKN2A copy number loss was associated with poor survival in HNSCCs stratified by HPV status. Methods: We analyzed The Cancer Genome Atlas (TCGA) head and neck cancer data, integrating genomic measurements with clinical metadata. Patients 85 years old or younger with a primary tumor in the oral cavity, oropharynx, hypopharynx, or larynx were included. Defining CDKN2A copy number loss as a relative log2 copy number ratio < −0.6, CDKN2A mRNA and p16 protein expression levels were compared to confirm significant differences in gene transcription and translation between the copy number loss and non-copy number loss patient groups. Overall survival (OS) and disease-free survival (DFS) were evaluated to characterize prognostic differences between genomic groups. Results: 397 patients negative for HPV (HPV−) and 91 patients positive for HPV (HPV+) HNSCC were identified. 139 HPV− patients and 9 HPV+ patients demonstrated CDKN2A copy number loss. The CDKN2A copy number loss group expressed significantly lower levels of CDKN2A mRNA and p16 protein than did the non-copy number loss group in both HPV+ and HPV− disease. Median OS for HPV− patients with and without CDKN2A copy number loss was 21.8 months and 46.0 months (P = 0.02). Median DFS was 12.0 and 19.4 months respectively (P < 0.05). Median OS for HPV+ patients with and without CDKN2A copy number loss was 12.7 months and 57.4 months (P = 0.004) and median DFS was 7.0 and 36.6 months respectively (P = 0.02). Conclusions: CDKN2A copy number loss was associated with low CDKN2A mRNA and p16 protein expression, with poor prognosis in terms of disease-free and overall survival.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 486-486
Author(s):  
Takahiro Yoneyama ◽  
Hirotake Kodama ◽  
Shogo Hosogoe ◽  
Ayumu Kusaka ◽  
Noriko Tokui ◽  
...  

486 Background: Systemic inflammation is a common host reaction to cancer progression. Serum level of buttyrylcholinesterase (BChE) have been reported to reflect the presence of inflammation and other clinical conditions. BChE is an alphaglycoprotein found in the nervous system and liver. Its serum level is reduced in many clinical conditions, such as liver damage, injury, infection, and malignant disease. We retrospectively evaluated the potential prognostic significance of buttyrylcholinesterase before chemotherapy as an independent predictor of overall survival in patients with advanced upper-tract urothelial cancer. Methods: We treated seventy-four patients (52 men and 22 women) with advanced upper-tract urothelial cancer (UTUC) at our clinic between August 2004 and September 2017. The average age was 69.3 (43–89), and average eGFR was 50.5 (11.6–99.3) ml/minute/1.73m2. Mean observation period was 28.7 (3–111) months. Levels of serum BChE (normal range 168-470 U/L) were measured 1 week before chemotherapy. The average serum level of BChE were 240.6 U/L (53-509). The patients received 2 courses of GCarbo consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCcarbo was performed. If this regimen did not induce any tumor size reduction, we switched to 2 courses of GCarboD (D; 70mg/m2) treatment as second-line treatment. Results: GCarbo regimen yielded 5 cases (6.8%) of CR, 32 (43.2%) of PR, and the average duration of response of 11.4 (2–29) months. GCarboD treatment was administered in 21 cases, and yielded 2 (9.5%) PR and a duration of response was 31.5(7-50) months. The median over-all survival period was 14.3 months. When analyzed by serum BChE level, the ovearall survival were 22.0 months in the BChE > 168 U/L group and 11.0 months in the BChE < 168 group (p = 0.0035). The level of serum BChE showed no association with treatment effect. Conclusions: Serum BChE level before chemotherapy may have the potential to predict overall survival in patients with advanced upper-tract urothelial cancer.


2020 ◽  

Purpose: The present study aims to evaluate the incidence of signet ring cell (SRC) histology in patients with gastric cancer and its prognostic significance on the disease stage. Methods: Between November 2006 and September 2019, 309 patients were reviewed retrospectively in Kartal Koşuyolu High Specialization Training and Research Hospital Gastroenterology Surgery clinic in Turkey and the clinicopathological features and survival status were examined in the presence of ring cell histology. Results: Of the patients, 71.4% had gastric cancer with a non-SRC histology and 28.6% had an SRC histology. The presence of an SRC histology was found to be associated with young age (p=0.007), advanced depth of wall invasion (p=0.001), number of positive lymph nodes (p=0.022) and presence of vascular invasion (p=0.044). The presence of an SRC histology was associated with good prognosis in patients with stage I gastric cancer (p=0.045), but with poor prognosis in patients with stage III disease (p=0.034). The study found no significant association between stage II disease and overall survival. Conclusions: The present study found survival to be associated with good prognosis in stage I, and poor prognosis in stage III among patients with gastric cancer with SRC histology. No prognostic significance could be established for overall survival.


2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Shitong Lin ◽  
Canhui Cao ◽  
Yifan Meng ◽  
Ping Wu ◽  
Peipei Gao ◽  
...  

Abstract Purpose: Several RAB family genes have been studied extensively and proven to play pivotal roles in the occurrence and development of certain cancers. Here, we explored commonly expressed RAB family genes in humans and their prognostic significance using bioinformatics, and then identified potential biomarkers of breast invasive carcinoma (BRCA). Materials and methods: The prognostic values (overall survival) of RAB family genes in BRCA were obtained using Gene Expression Profiling Interactive Analysis (GEPIA). The expression patterns of RAB family genes and their relationships with clinicopathological parameters in BRCA were measured using the ONCOMINE and UALCAN databases, respectively. Genetic mutations and survival analysis were investigated using the cBio Cancer Genomics Portal (c-BioPortal). Interacting genes of potential biomarkers were identified using STRING, and functional enrichment analyses were performed using FunRich v3.1.3. Results: In total, 64 RAB genes were identified and analyzed in our study. Results showed that RAB1B, RAB2A, and RAB18 were up-regulated and significantly associated with poor overall survival in BRCA. Furthermore, their higher expression was positively correlated with clinicopathological parameters (e.g. cancer stage and nodal metastasis status). DNA copy number amplifications and mRNA up-regulation were the main genetic mutations, and the altered group showed significantly poorer overall survival compared with the unaltered group. Functional enrichment analysis of RAB1B, RAB2A, and RAB18 indicated they were closely involved in GTPase activity. Conclusions:RAB1B, RAB2A, and RAB18 were up-regulated and significantly correlated with poor prognosis in BRCA. Thus, they could be applied as novel biomarkers of BRCA in future studies.


2020 ◽  
Vol 129 (9) ◽  
pp. 863-871
Author(s):  
Mariem Ben Elhadj ◽  
Asma Fourati ◽  
Olfa El Amine ◽  
Aida Goucha ◽  
Ahmed El May ◽  
...  

Objectives: Tobacco and alcohol are the main etiological factors common to laryngeal cancers. However, the Human Papilloma Virus (HPV) constitutes an alternative risk factor according to several studies. In Tunisia, despite the annual increasing incidence of laryngeal squamous cell carcinoma (LSCC), the prevalence and prognostic significance of HPV have never been explored. In this study, we sought to highlight HPV DNA in 70 biopsies of laryngeal cancer, and to analyze the status of HPV infection in association with p53, p16, survivin, and IGF-1R expressions. Methods: HPV high risk (HPV HR) DNA was detected in tumors by in situ hybridization. However, the expression of p53, p16, survivin and IGF-1R were stained by immunohistochemistry test. The correlations of HPV status with clinicopathological parameters, overall survival, disease-free survival and proteins expressions were statistically evaluated. Results: HPV HR DNA was detected in 39 out of 70 (55.71%) laryngeal tumors. HPV+ patients have a better overall survival ( P = .081) and long disease-free-survival ( P = .016) with a low rate of recurrence ( P = .006) than HPV– patients. No significant correlations were found between HPV HR status and clinicopathological parameters (all P > .005). Moreover, HPV+ tumors were not associated with expression of p53, p16 and survivin. However, HPV HR status correlates with weak to moderate IGF-1R expression ( P = .043). Conclusion: The substantial detection of HPV HR in LSCC tumors suggest that this virus plays an important part in laryngeal cancer in Tunisia. It is a good prognostic factor. In addition, HPV infection could act to block the pathway of IGF-1R expression.


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