CHARACTERISTICS OF THE IMMUNE MICROENVIRONMENT OF THE NORMAL MUCOUS MEMBRANE OF THE PERITUMORAL AREA IS AN ADDITIONAL INDEPENDENT PROGNOSTIC FACTOR IN GASTRIC CANCER

The aim of the study was to study and evaluate the predictive value of the immune microenvironment of gastric cancer and morphologically normal mucous membrane of the peritumoral area using an automatic morphometric analysis system on the example of CD 8+ cells.Material and Methods. Surgical samples from 130 patients with a verified diagnosis of gastric cancer were used. After immunohistochemical staining with antibodies to CD 8, a morphological assessment was performed according to the original method. We assessed the average area of CD 8+ cells in three fields of view (lens magn. ×20) using the automatic system of morphometric analysis LAS X (Leica) in the central part of the tumor and areas of morphologically normal mucous membrane of the peritumoral region directly adjacent to the tumor tissue. The results were compared with the main clinical and morphological characteristics of the tumor as well as with the overall five-year survival of patients.Results and Discussion. A high density of CD 8+ infiltration of normal mucous membrane of the peritumoral area was observed in groups T4a and T4b by the depth of invasion (n=96, p=0.0089) and was associated with the presence of emboli in the lymphatic vessels (n=96, p=0.0102) and with the more advanced stage of gastric cancer (n=96, p=0.0107). The studied cases were divided into two groups: less than 3300 square micrometers (better patient survival; n=79, p=0.01) and more than 3300 square micrometers according to the average area of CD 8+ cells in normal mucous membrane of the peritumoral area. According to multivariate survival analysis using the Cox regression model, it was found that the average area of CD 8+ cells in normal mucous membrane of the peritumoral area was a significant negative prognostic factor (RR=1.537; CI : 0.761–3.105; p<0.01) comparable in degree covariance with the stage of the tumor A similar indicator assessed in central part of the tumor was not significantly associated with patient survival (RR=0.803; CI : 0.574–1.122; p>0.05).Conclusion. The possibility of using an automatic analysis system to evaluate the immune microenvironment in gastric cancer was demonstrated for the first time. It was found that a high level of CD 8+ lymphocyte infiltration of morphologically normal mucous membrane of the peritumoral area was an independent negative prognostic factor. Therefore, we recommend the mandatory preoperative biopsy sampling from the mucous membrane of the peritumoral region for morphometric assessment of CD 8+ lymphocyte infiltration.

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Expression of Cytoplasmic TFF2 Is a Marker of Tumor Metastasis and Negative Prognostic Factor in Gastric Cancer

Laboratory Investigation ◽

10.1097/01.lab.0000085190.99749.15 ◽

2003 ◽

Vol 83 (9) ◽

pp. 1343-1352 ◽

Cited By ~ 36

Author(s):

Dipok Kumar Dhar ◽

Timothy C Wang ◽

Riruke Maruyama ◽

Jun Udagawa ◽

Hirofumi Kubota ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Factor ◽

Tumor Metastasis ◽

Negative Prognostic Factor

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Oestrogen receptor D5 antibody is an independent negative prognostic factor in gastric cancer

British Journal of Surgery ◽

10.1002/bjs.1800780321 ◽

1991 ◽

Vol 78 (3) ◽

pp. 334-336 ◽

Cited By ~ 36

Author(s):

J. D. Harrison ◽

J. A. Jones ◽

I. O. Ellis ◽

D. L. Morris

Keyword(s):

Gastric Cancer ◽

Prognostic Factor ◽

Oestrogen Receptor ◽

Negative Prognostic Factor ◽

Independent Negative Prognostic Factor

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Plasma biomarker analysis of ramucirumab in Japanese patients with advanced gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.81 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 81-81 ◽

Cited By ~ 1

Author(s):

Daisuke Takahari ◽

Takeru Wakatsuki ◽

Tetsuo Mashima ◽

Keisho Chin ◽

Takashi Ichimura ◽

...

Keyword(s):

Gastric Cancer ◽

Multivariate Analysis ◽

Prognostic Factor ◽

Advanced Gastric Cancer ◽

Base Line ◽

Plasma Biomarker ◽

Negative Prognostic Factor ◽

Biomarker Analysis ◽

Single Use ◽

Independent Negative Prognostic Factor

81 Background: Ramucirumab, anti-VEGFR2 receptor antibody, showed significantly improved survivals of gastric cancer in the second line with paclitaxel or single use. Recently we reported early elevation of plasma VEGF-A was associated with shorter survival as a preliminary result. We will report the results of final analysis. Methods: Patients with advanced gastric cancer who received ramucirumab combined with paclitaxel or single use were enrolled. Plasma samples were collected at pre-treatment and day 8 after administration. Nine kinds of plasma biomarker involved in angiogenesis, VEGF-A, C, D, PlGF, VEGFR1, 2, Angiopoietin 1, stromal cell derived factor-1α (SDF1α), and Neuropirin-1, were measured by means of ELISA. Patients were dichotomized by optimal cut-off value. Univariate and multivariate analysis were done by Cox proportion hazard model. Results: Forty-one patients were enrolled. Thirty-nine patients (95.1%) received ramucirumab with paclitaxel. Plasma VEGF-A, D, PlGF, and VEGFR2 levels were significantly increased one week after administration compared with baseline levels, while plasma VEGFR1 and NRP1levels were significantly decreased. Median PFS and OS were 5.6 (95% CI 4.66-6.54) and 9.8 (95% CI 5.41-14.19) months, respectively. In univariate analysis, higher baseline SDF1α and PlGF levels resulted in shorter OS with HR 2.71 95% CI 1.23-6.00, p =0.013 for SDF1α and HR 2.78 95% CI 1.16-6.65, p =0.022 for PlGF. Higher D8 VEGF-A was associated with shorter PFS with HR 2.77 95% CI 1.39-5.51, p =0.004. While higher D8 VEGF-D was associated with better PFS with HR 0.39 95% CI 0.20-0.77, p =0.007. In multivariate analysis, higher baseline SDF1α and PlGF were independent negative prognostic factor for OS with HR 2.45 95% CI 1.10-5.42, p =0.028 for SDF1α and HR 2.48 95% CI 1.03-5.96, p =0.043. With respect to PFS, higher D8 VEGF-A was also independent negative prognostic factor with HR 2.32 95% CI 1.13-4.77, p =0.022, while higher D8 VEGF-D was favorable predictor for PFS with HR 0.47 95% CI 0.23-0.96, p =0.038. Conclusions: Higher base line SDF1α and PlGF levels may be negative prognostic marker. While early VEGF-A and D elevation after ramucirumab administration may be predictive marker of ramucirumab.

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Analysis of weight loss as a prognostic factor in patients (pts) with advanced gastric cancer from REGARD, RAINBOW and RAINFALL phase III studies.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.348 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 348-348

Author(s):

Wasat Mansoor ◽

Eric Roeland ◽

Aafia Chaudhry ◽

Ran Wei ◽

Anindya Chatterjee ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Factor ◽

Advanced Gastric Cancer ◽

Meta Analysis ◽

Phase Iii ◽

Phase 3 ◽

Nutritional Interventions ◽

Negative Prognostic Factor ◽

Three Phase ◽

The Impact

348 Background: Maintaining weight (wt) and adequate nutrition during systemic treatment in advanced gastric cancer (G/GEJ) therapy remains a challenge. We investigated the impact of early wt-loss on survival in three phase 3 studies of ramucirumab (R); REGARD (RG), RAINBOW (RB), and RAINFALL (RF) in G/GEJ. Methods: ITT pts were categorized into 2 groups based on their body wt change from start to end of cycle 1 (C1; C = 28 days in RG, RB; C = 21 days in RF): wt-loss < 3% vs ≥3%. Univariate Cox PH models were performed in each individual study to evaluate the effects of body wt change from the start to end of C1 on OS. A pooled meta-analysis stratified by study and a sensitivity analysis of the subgroup of responders was also performed. Results: A total of 311 (RG: 212 in R+BSC; 99 in Placebo (PB)+BSC), 591 (RB: 306 in the R+Paclitaxel (P); 285 PB+P), and 562 (RF: 279 in R+Cape/Cis (CC); 283 in PB+CC) pts with body wt data during C1 were evaluated. The number of pts with wt-loss of ≥3% and < 3% are shown in Table. Pts with wt-loss < 3% during C1 experienced longer OS compared to those with wt-loss ≥3%, irrespective of treatment arms across studies (Table). In pooled treatment arms within each study, the HR for wt-loss group ( < 3% vs ≥3%) was 0.359 (95% CI = 0.254, 0.507), 0.632 (0.497, 0.804), 0.752 (0.608, 0.930) in RG, RB, RF, respectively. In the meta-analysis that combined the 3-studies, univariate Cox PH model stratified by study showed consistent effect of early wt-loss on OS regardless of treatment arm, HR ( < 3% vs ≥3%) = 0.632 (0.546, 0.732). Conclusions: Analysis from three phase 3 studies demonstrates early wt-loss ≥3% during C1 is an important negative prognostic factor for survival in gastric/GEJ cancer. Prospective studies of the relationship of weight preserving nutritional interventions on OS are warranted. Clinical trial information: NCT00917384, NCT01170663, NCT02314117. [Table: see text]

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Stromal score as a prognostic factor in primary gastric cancer and close association with tumor immune microenvironment

Cancer Medicine ◽

10.1002/cam4.2801 ◽

2020 ◽

Vol 9 (14) ◽

pp. 4980-4990

Author(s):

Min Mao ◽

Qingliang Yu ◽

Rongzhi Huang ◽

Yunxin Lu ◽

Zhen Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Factor ◽

Close Association ◽

Immune Microenvironment ◽

Primary Gastric Cancer ◽

Tumor Immune Microenvironment

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High level of Serum AFP is an Independent Negative Prognostic Factor in Gastric Cancer

The International Journal of Biological Markers ◽

10.5301/jbm.5000167 ◽

2015 ◽

Vol 30 (4) ◽

pp. 387-393 ◽

Cited By ~ 8

Author(s):

Yueguang Chen ◽

Hui Qu ◽

Mi Jian ◽

Guorui Sun ◽

Qingsi He

Keyword(s):

Gastric Cancer ◽

Liver Metastasis ◽

Prognostic Factor ◽

Clinicopathological Features ◽

Independent Prognostic Factor ◽

Prognostic Features ◽

Negative Prognostic Factor ◽

Serum Alpha Fetoprotein ◽

Gastric Cancer Patients ◽

High Level

Background Gastric cancer with a high level of serum alpha fetoprotein (AFP) is uncommon and has unique clinicopathological features and a poorer prognosis. The aim of this research was to elucidate the clinicopathological and prognostic features of gastric cancer with a high level of AFP. Methods The sera from 1,286 patients with gastric cancer treated at Qilu Hospital of Shandong University from January 2004 to December 2008 were analyzed preoperatively for AFP, CEA and CA19-9 levels after excluding active or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma as well as preoperative distant metastasis. Patients were divided into 2 groups: 86 serum AFP-positive patients and 1,200 serum AFP-negative patients according to a cutoff of 20 ng/mL. The clinicopathological features and prognostic factors were compared between the groups. Results A higher incidence of serosal invasion, lymph node metastasis and liver metastasis and poorer prognosis was observed in the AFP-positive group compared with the AFP-negative group (all p<0.05). Serum AFP showed the highest specificity (93.66%) and diagnostic accuracy (92.38%) for predicting liver metastasis among the 3 tumor markers examined. Multivariate survival analysis revealed that AFP positivity was an independent prognostic factor in all 1,286 gastric cancer patients. The prognosis of AFP-positive gastric cancer was poorer than that of AFP-negative gastric cancer (p<0.05). Conclusions A high level of serum AFP is an independent prognostic factor in gastric cancer and can be used for evaluating the prognosis of gastric cancers whether in the presence or absence of liver metastasis.

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