CD44+ cytokeratin-positive tumor cells in blood and bone marrow are associated with poor prognosis of patients with gastric cancer

PURPOSE: To study the invasion-related molecule urokinase-type plasminogen activator receptor (u-PAR) expressed by disseminated tumor cells as a biologic predictor of poor survival in a large prospective series of patients with gastric cancer. PATIENTS AND METHODS: In 156 gastric cancer patients (prospective series), disseminated tumor cells in the bone marrow and the u-PAR expressed by these tumor cells were determined by cytokeratin (CK) 18 immunocytochemistry and u-PAR/CK18 double immunocytochemistry. RESULTS: In contrast to the mere detection of disseminated tumor cells at primary surgery, the additional evidence of u-PAR on these cells correlated significantly with pathologic T stage (P = .0474) and the expression of u-PAR (P = .0093) and plasminogen-activator inhibitor 1 (P = .0145) in the primary tumor (immunohistochemistry, χ2). Kaplan-Meier analysis revealed no association with prognosis for the mere detection of disseminated tumor cells. In contrast, a significant association was seen between detection of u-PAR on these cells and shorter disease-free (P < .0001) and overall survival (P < .0001). Multivariate analysis revealed that u-PAR on disseminated tumor cells at the time of primary surgery is an independent prognostic factor for disease-free (95% confidence interval [CI], 1.72 to 3.21; P = .024) and overall survival (P = .0049; relative risk, 2.89; 95% CI, 1.92 to 4.30). CONCLUSION: This is the first large study to show that u-PAR, detected on disseminated tumor cells in the bone marrow, is an independent prognostic parameter in gastric cancer, in contrast to the mere detection of minimal residual disease (MRD). u-PAR may be a promising marker to define a critical subpopulation of disseminated tumor cells and a target to eliminate MRD. Molecular phenotyping of MRD is critical for defining its individual clinical relevance.

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Disseminated Tumor Cells in Bone Marrow of Gastric Cancer Patients: Correlation with Tumor Hypoxia and Clinical Relevance

Journal of Oncology ◽

10.1155/2014/582140 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Larissa Bubnovskaya ◽

Antonina Kovelskaya ◽

Lilya Gumenyuk ◽

Irina Ganusevich ◽

Lesya Mamontova ◽

...

Keyword(s):

Gastric Cancer ◽

Bone Marrow ◽

Overall Survival ◽

Tumor Cells ◽

Clinical Relevance ◽

Tumor Hypoxia ◽

Disseminated Tumor Cells ◽

Vegf Expression ◽

Primary Tumors ◽

Gastric Cancer Patients

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.

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Aneuploidy of tumor cells in cases of gastric cancer with esophageal invasion: Another indicator of poor prognosis

Journal of Surgical Oncology ◽

10.1002/jso.2930580203 ◽

1995 ◽

Vol 58 (2) ◽

pp. 83-90 ◽

Cited By ~ 5

Author(s):

Masahide Ikeguchi ◽

Satoshi Ohfuji ◽

Atsuo Oka ◽

Shunichi Tsujitani ◽

Michio Maeta ◽

...

Keyword(s):

Gastric Cancer ◽

Tumor Cells ◽

Poor Prognosis ◽

Esophageal Invasion

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CXCR4 Expression in Gastric Cancer and Bone Marrow: Association with Hypoxia-Regulated Indices, Disseminated Tumor Cells, and Patients Survival

Journal of Cancer Research ◽

10.1155/2015/980214 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8

Author(s):

Dmitry Osinsky ◽

Antonina Kovelskaya ◽

Larissa Bubnovskaya ◽

Irina Ganusevich ◽

Lilya Gumenyuk ◽

...

Keyword(s):

Gastric Cancer ◽

Bone Marrow ◽

Overall Survival ◽

Tumor Cells ◽

Clinical Characteristics ◽

Tumor Hypoxia ◽

Disseminated Tumor Cells ◽

Cxcr4 Expression ◽

Unfavourable Outcome ◽

Vegf Expression

Aim. The analysis of the association of CXCR4 expression in gastric cancer (GC) and bone marrow (BM) with clinical characteristics. Patients and Methods. 65 patients with GC were investigated. Immunohistochemistry, immunocytochemistry, NMR-spectroscopy, and zymography were used. Results. CXCR4 was expressed in 78.5% of GC specimens and correlated with tumor hypoxia (P<0.05), VEGF expression (P<0.01), and gelatinases activity (P<0.05). CXCR4-positive cells in GC were detected in 80% of patients with disseminated tumor cells (DTCs). Overall survival (OS) of patients with CXCR4-positive tumors was poorer than that of patients with CXCR4-negative tumors (P=0.037). The CXCR4-positive cells in BM were found in 46% of all patients and in 56% of patients with DTCs. CXCR4 expression in BM was not associated with OS. Risk of unfavourable outcome is increased in patients with CXCR4-positive tumors (P<0.05). CXCR4 expression in BM was positively associated with DTCs, especially in patients with M0 category. Risk of unfavourable outcome is increased in patients with M0 category and with both CXCR4-positive BM and DTCs (P=0.03). Conclusions. CXCR4 expression in tumor was positively correlated with hypoxia level and VEGF expression in tumor as well as OS. CXCR4 expression in BM is associated with DTCs.

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Early detection of tumor cells in bone marrow and peripheral blood in a fast‑progressing gastric cancer model

International Journal of Oncology ◽

10.3892/ijo.2021.5171 ◽

2021 ◽

Vol 58 (3) ◽

pp. 388-396

Author(s):

Prerna Bali ◽

Ivonne Lozano‑Pope ◽

Collin Pachow ◽

Marygorret Obonyo

Keyword(s):

Gastric Cancer ◽

Bone Marrow ◽

Early Detection ◽

Tumor Cells ◽

Peripheral Blood ◽

Cancer Model

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Detection of disseminated tumor cells in bone marrow of gastric cancer using magnetic activated cell sorting and fluorescent activated cell sorting

Journal of Gastroenterology and Hepatology ◽

10.1111/j.1440-1746.2008.05633.x ◽

2009 ◽

Vol 24 (2) ◽

pp. 299-306 ◽

Cited By ~ 9

Author(s):

Gui-Ying Wang ◽

Yong Li ◽

Yue-Ming Yu ◽

Bin Yu ◽

Zhen-Ya Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Bone Marrow ◽

Tumor Cells ◽

Cell Sorting ◽

Disseminated Tumor Cells ◽

Magnetic Activated Cell Sorting

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A case of disseminated carcinomatosis of the bone marrow from gastric cancer developing rapidly after a gastrectomy

Surgical Case Reports ◽

10.1186/s40792-021-01135-5 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Shunsuke Sato ◽

Yuji Ishibashi ◽

Koichiro Kawasaki ◽

Ryoto Yamazaki ◽

Fumihiko Hatao ◽

...

Keyword(s):

Gastric Cancer ◽

Bone Marrow ◽

Poor Prognosis ◽

Laboratory Tests ◽

Distal Gastrectomy ◽

Postoperative Bleeding ◽

Laboratory Data ◽

Severe Thrombocytopenia ◽

Case Presentation ◽

Lower Back

Abstract Background Disseminated carcinomatosis of the bone marrow (DCBM) is often associated with disseminated intravascular coagulation (DIC) and a poor prognosis. Moreover, the timing of the diagnosis varies. We presented herein the first report of a case of DCBM from gastric cancer that developed rapidly after a gastrectomy. Case presentation A 42-year-old male patient was referred to us for gastric cancer. Preoperative laboratory tests were normal. Abdominal computed tomography (CT) revealed no obvious bone metastasis, and he underwent a laparoscopic distal gastrectomy. On postoperative day (POD) 1, laboratory data indicated severe thrombocytopenia. Postoperative bleeding requiring reoperation was found. Afterwards, he complained of lower back pain. His ALP and LDH gradually became elevated. On POD 8, DIC was diagnosed. CT and bone scintigraphy showed multiple, widespread bone metastases. Based on these findings, DCBM from gastric cancer was diagnosed. Systemic chemotherapy was started on POD 12. The DIC subsided during the first course, and he was discharged on POD 21. The patient died of tumor progression 7 months later. Conclusion When thrombocytopenia is observed immediately after a gastrectomy for gastric cancer, the possibility of DCBM should be considered.

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Early detection of biomarkers for circulating tumor cells in Bone marrow and Peripheral blood in a fast-progressing gastric cancer model

10.1101/2020.01.29.925727 ◽

2020 ◽

Author(s):

Prerna Bali ◽

Ivonne Lozano-Pope ◽

Collin Pachow ◽

Marygorret Obonyo

Keyword(s):

Gastric Cancer ◽

Bone Marrow ◽

Early Detection ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Peripheral Blood ◽

Post Infection ◽

Cancer Metastasis ◽

Cancer Model ◽

Emt Markers

AbstractHelicobacter pylori poses one of the greatest risks for development of gastric cancer. We previously established a crucial role for myeloid differentiation primary response 88 (MyD88) in the regulation of Helicobacter-induced gastric cancer. Mice deficient in Myd88 rapidly progressed to neoplasia when infected with H. felis, a close relative of H. pylori. For this study we examined circulating tumor cells (CTCs) by measuring expression of cytokeratins, epithelial to mesenchymal transition (EMT) and cancer stem cell (CSC) markers in in the bone marrow and peripheral blood of gastric cancer models we termed fast (Myd88-/-)- and slow (WT)-“progressors”. We detected cytokeratins CK8/18 as early as 3 months post infection in the fast “progressors”. In contrast, cytokeratins were not detected in slow “progressor” gastric cancer model even after 7 months post infection. Expression of MUC1 was observed in both bone marrow and peripheral blood at different time points suggesting its role in gastric cancer metastasis. Snail, Twist and ZEB were expressed at different levels in bone marrow and peripheral blood. Expression of these EMT markers suggests manifestation of cancer metastasis in the early stages of disease development. Lgr5, CD44 and CD133 were the most prominent CSC markers detected. Detection of CSC and EMT markers along with cytokeratins does reinforce their use as biomarkers for gastric cancer metastasis. This early detection of markers suggests that CTCs leave primary site even before cancer is well established. Thus, cytokeratins, EMT, and CSCs could be used as biomarkers to detect aggressive forms of gastric cancers. This information will be important in stratifying patients for treatment before the onset of severe disease characteristics.

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