Clinicopathological and prognostic significance of microsatellit instability (MSI) status and PDl-1 expression in Turkish patients with gastric cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15538-e15538
Author(s):  
Ibrahim Yildiz ◽  
Seyma Bahsi ◽  
Sibel Erdamar ◽  
Suha Goksel ◽  
Gokhan Demir ◽  
...  

e15538 Background: The aim of this study was to evaluate the prognostic role of microsatellite instability (MSI) status and PD-L1 expression in surgically resected gastric cancer and the relationship of these parameters with clinicopathological features. Methods: Eighty six gastric cancer patients which had curative surgical resection at Acibadem Atakent and Maslak Hospitals between 2010 and 2017 were analysed. Tumor samples were evaluated with MSI and PD-L1 antibodies by immunohistochemical (IHC) methods. PD-L1 IHC scoring was performed using the combined positive score (CPS). Survival analysis was accomplished using the Kaplan-Meier method. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival. Results: The rate of PD-L1 expression in tumor cells was 34.9% (n = 30) and the frequency of PD-L1 expression in immune cells with CPS (≥1%) was 57% (n = 49). MSI-H was detected in 11.6%(n = 10), and more observed in PD-L1 positive cases (p = 0.021). MSI-H status was significantly correlated with older age, increased tumor size, presence of PD-L1 expression, and adenocarcinoma subtype. PD-L1 expression was associated with lymph node metastasis, adenocarcinoma subtype, microsatellite instability, presence of preoperative treatment and improved response to preoperative chemotherapy. In our study, the impact of MSI status on survival was not demonstrated, but PD-L1 expression positivity(≥1%) in both tumor cells (15.7 vs 53.4 months, p = 0.008)and in immune cells (20.4 vs NR; p = 0.027) was associated with short overall survival. PD -L1 expression in tumor cells was an independent prognostic factor for overall survival in multivariate analysis (HR: 2.28, p = 0.047). Conclusions: PD-L1 expression was related to a poor prognosis in patients with gastric cancer and can represent a rational approach for PD-1/PD-L pathway-targeted immunotherapy.

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 198
Author(s):  
Ji Yeon Park ◽  
Byunghyuk Yu ◽  
Ki Bum Park ◽  
Oh Kyoung Kwon ◽  
Seung Soo Lee ◽  
...  

Background and Objectives: The prognosis of metastatic or unresectable gastric cancer is dismal, and the benefits of the palliative resection of primary tumors with noncurative intent remain controversial. This study aimed to evaluate the impact of palliative gastrectomy (PG) on overall survival in gastric cancer patients. Materials and Methods: One hundred forty-eight gastric cancer patients who underwent PG or a nonresection (NR) procedure between January 2011 and 2017 were retrospectively reviewed to select and analyze clinicopathological factors that affected prognosis. Results: Fifty-five patients underwent primary tumor resection with palliative intent, and 93 underwent NR procedures owing to the presence of metastatic or unresectable disease. The PG group was younger and more female dominant. In the PG group, R1 and R2 resection were performed in two patients (3.6%) and 53 patients (96.4%), respectively. The PG group had a significantly longer median overall survival than the NR group (28.4 vs. 7.7 months, p < 0.001). Multivariate analyses revealed that the overall survival was significantly better after palliative resection (hazard ratio (HR), 0.169; 95% confidence interval (CI), 0.088–0.324; p < 0.001) in patients with American Society of Anesthesiologists Physical Status (ASA) scores ≤1 (HR, 0.506; 95% CI, 0.291–0.878; p = 0.015) and those who received postoperative chemotherapy (HR, 0.487; 95% CI, 0.296–0.799; p = 0.004). Among the patients undergoing palliative resection, the presence of <15 positive lymph nodes was the only significant predictor of better overall survival (HR, 0.329; 95% CI, 0.121–0.895; p = 0.030). Conclusions: PG might lead to the prolonged survival of certain patients with incurable gastric cancer, particularly those with less-extensive lymph-node metastasis.


2010 ◽  
Vol 13 (3) ◽  
pp. 191-196 ◽  
Author(s):  
Takeo Fukagawa ◽  
Mitsuru Sasako ◽  
Seiji Ito ◽  
Hayao Nakanishi ◽  
Hisae Iinuma ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Larissa Bubnovskaya ◽  
Antonina Kovelskaya ◽  
Lilya Gumenyuk ◽  
Irina Ganusevich ◽  
Lesya Mamontova ◽  
...  

Aim.The evaluation of the clinical relevance of disseminated tumor cells (DTCs) in bone marrow (BM) of patients with gastric cancer (GC) and their association with primary tumor hypoxia.Patients and Methods.89 resected specimens were used. DTCs were detected using immunocytochemistry, the level of tumor hypoxia using NMR spectroscopy, CD68, CD34, VEGF, and VEGFR-1 (Flt-1) expression using immunohistochemistry, and MMP-2 and MMP-9 activity using zymography.Results.DTCs were detected in 51.4% of GC patients with M0. There was significant correlation between frequency of DTCs in BM and level of tumor hypoxia (P<0.024). DTCs presence was accompanied with Flt-1 positivity of BM. The correlation between DTCs and tumor VEGF expression in patients with M0was shown (P<0.0248). Activity of MMP-2 and MMP-9 in BM was linked with DTCs in patients with M0(P<0.05). Overall survival (OS) of patients with M0and DTCs was shorter than that of patients without DTCs (patients in both groups were operated only) (P=0.0497).Conclusion.Appearance of DTCs correlates with hypoxia level in primary tumors. Detection of DTCs in GC patients may be relevant indicator for adjuvant chemotherapy using.


2006 ◽  
Vol 22 (3) ◽  
pp. 103-109 ◽  
Author(s):  
C. H. Wu ◽  
S. R. Lin ◽  
J. S. Hsieh ◽  
F. M. Chen ◽  
C. Y. Lu ◽  
...  

Early detection of disseminated tumor cells in the peripheral blood of patients with early stage gastric cancer could help to improve the outcome after tumor resection. The aim of this study is to evaluate the prognostic significance of tumor-related mRNA for the detection of circulating tumor cells in gastric cancer patients by a reverse-transcriptase polymerase chain reaction (RT-PCR) method. We simultaneously analyzed human telomerase reverse transcriptase (hTERT), cytokeratin-19 (CK-19), cytokeratin-20 (CK-20) and carcinoembryonic antigen (CEA) mRNA (messenger RNA) expression in the peripheral blood of 42 gastric cancer patients and 30 healthy individuals. Additionally, analyses were carried out for the correlation of these four molecular markers with patients’ clinicopathologic features, as well as the occurrence of postoperative recurrence/metastasis. Among 42 gastric cancer patients, the prevalence of mRNA for hTERT, CK-19, CK-20, and CEA was 61.9% (26/42), 69% (29/42), 61.9% (26/42), and 78.6% (33/42), respectively. All 30 healthy individuals were negative for hTERT and CEA mRNA, while two were positive for either CK-19 mRNA or CK-20 mRNA. Positive CEA mRNA was significantly correlated with tumor size (p= 0.008), vessel invasion (p= 0.001), depth of tumor invasion (p= 0.007), lymph node metastasis (p< 0.001), and TNM stage (p< 0.001). In addition, the multivariate logistic regression demonstrated that CEA mRNA expression was an independent and significant predictor for postoperative recurrence/metastasis (p= 0.032). Our findings suggest that CEA mRNA may be a more reliable marker than hTERT, CK-19 and CK-20 for the detection of circulating cancer cells in gastric cancer patients' peripheral blood. Patients with positive CEA mRNA expression in peripheral blood have a significantly higher risk of postoperative recurrence/metastasis.


2019 ◽  
Vol 34 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Yan Jin ◽  
Kun Zhou ◽  
Wenjing Zhao ◽  
Rongbo Han ◽  
Xinying Huo ◽  
...  

Background: The gene metastasis-associated in colon cancer-1 (MACC1) has been reported to be overexpressed in diverse human malignancies, and an increasing amount of evidence suggests that its overexpression is associated with the development and progression of many human tumors. However, the prognostic and clinicopathological value of MACC1 in gastric cancer remains inconclusive. Therefore, we conducted this meta-analysis to investigate the effect of positive MACC1 expression on clinicopathological features and survival outcomes in gastric cancer. Methods: Medline, Web of Science, and EMBASE databases were searched for relevant articles published up to 10 April 2018. The correlation of MACC1 expression levels with overall survival and clinicopathological features was analyzed. Results: In this meta-analysis, nine studies with a total of 2103 gastric cancer patients were included. Our results showed that high expression of MACC1 was significantly related to a poor overall survival. Moreover, our meta-analysis showed that MACC1 overexpression was significantly linked to distant metastasis and vascular invasion. There were no significant correlations between positive MACC1 expression and gender, localization, tumor-node-metastasis (TNM) stage, tumor extent (T stage) and lymph node involvement (N stage) Conclusions: MACC1 expression levels can serve as a novel prognostic factor in gastric cancer patients.


Author(s):  
Mozaffar Aznab ◽  
Seyed Majid Ahmadi ◽  
Sedigheh Khazaei ◽  
Sedigheh Khazaei ◽  
Seyed Mojtaba Ahmadi ◽  
...  

Background: Thymidylate synthase is one of the target enzymes of 5-fluorouracil. However, the clinical and prognostic significance of TS expression in gastric cancer has remained controversial. In this study, the expression of thymidylate synthase was evaluated in gastric cancer patients treated with combinational chemotherapy; moreover, the association between TS expression and clinicopathologic characteristics and overall survival of the patients were also assessed. Materials and Methods: In this descriptive study, 89 pathological samples were gathered from patients at Kermanshah hospitals during 2008-2017. The survival status of patients was recorded and their overall survival was evaluated individually. Results: The average survival period for low and high thymidylate synthase groups was 54 and 50 months, respectively, meaning higher survival time in the lower thymidylate group. But this difference was not statistically significant (log Rank=0.88). In addition, sex, stage, recurrence, and survival had no significant difference between the low and high expression of thymidylate synthase groups (p=0.89). Conclusion: The results clearly indicated that the level of thymidylate synthase is not a significant modulator of 5- fluorouracil in gastric cancer patients. Nevertheless, evaluation of the level of the enzymes and markers as well as their effects are highly recommended for accurate selection of chemotherapeutical strategies.


2021 ◽  
Vol 66 (3) ◽  
pp. 139-146
Author(s):  
Nikolay Evgenievich Kushlinskii ◽  
E. S. Gershtein ◽  
V. L. Chang ◽  
E. A. Korotkova ◽  
A. A. Alferov ◽  
...  

Analysis of long-term treatment results of 101 primary gastric cancer patients at various stages of the tumor process followed during 1 - 41 months (median - 6,4 months) from the onset of specific treatment are presented depending on the levels of soluble forms (s) of PD-1 receptor and its ligand PD-L1 in blood plasma. Overall survival assessed by Kaplan-Meyer analysis and with the help of Cox multiparametric regression model was applied as the criterion of prognostic value. It was found that at high (≥ 35 pg/ml) sPD-L1 levels in blood plasma, the overall survival of patients with gastric cancer was statistically significantly lower than at the marker’s levels below 35 pg / ml (p <0.045): 1-year survival comprised 78 and 96%, 2-year - 52 and 78%; 3-year - 40 and 61% at high and low sPD-L1 respectively. Median survival of patients with high plasma sPD-L1 comprised 29 months, of those with low sPD-L1 was not achieved during the whole follow-up period. This trend was observed not only in the total group of stage I-IV gastric cancer patients, but also in patients at the early stages of the disease, though sPD-L1 did not show an independent prognostic value in multiparametric model. At the same time, the overall survival of patients with gastric cancer did not depend on the baseline levels sPD-1 in blood plasma. Thus, soluble ligand sPD-L1 can be considered as a potentially valuable factor for prognosis of gastric cancer patients’ survival, and, probably, of anti-PD-1/PD-L1 treatment efficiency, but further studies and patients’ monitoring are required to prove this statement.


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