The significances of lymph node micrometastasis and its correlation with E‐cadherin expression in pT1‐T3N0 gastric adenocarcinoma

Kim, Jong Han; Park, Joong Min; Jung, Cheol Woong; Park, Sung Soo; Kim, Seungjoo; Mok, Young Jae; Kim, Chong Suk; Chae, Y. S.; Bae, Jeoung Won

doi:10.1002/jso.20937

Cited by 55 publications

(37 citation statements)

References 24 publications

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“…5 Lymph node metastasis (LNM) is generally responsible for the high mortality rate of gastric cancer. 6 Especially in recent years, the importance of lymph node micrometastasis (LNMM) has been increasingly recognized, 7 which is regarded as the supplement of current staging systems for predicting prognosis or planning adjuvant therapy. 8 However, it remains difficult to diagnose lymphatic metastasis preoperatively or to supervise its recurrence postoperatively by imaging tests, 9 let alone to diagnose the micrometastasis.…”

Section: Introductionmentioning

confidence: 99%

Cadherin-17 induces tumorigenesis and lymphatic metastasis in gastric cancer through activation of NFκB signaling pathway

Wang

Kang

et al. 2013

Cancer Biology & Therapy

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Section: Introductionmentioning

confidence: 99%

Cadherin-17 induces tumorigenesis and lymphatic metastasis in gastric cancer through activation of NFκB signaling pathway

Wang

Kang

et al. 2013

Cancer Biology & Therapy

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“…21 In addition, a relationship between SIRT1 activity and expression of the tumor suppressor adhesion molecule, E-cadherin, 22 is closely related to the metastatic potential of tumors. 23 This has led to the hypothesis that SIRT1 may promote tumorgenesis and drug resistance and provide a potential target for cancer therapy. 24,25 It has also been shown that SIRT1 may inhibit proliferation and tumor formation.…”

Section: Introductionmentioning

confidence: 99%

SIRT1 RNAi knockdown induces apoptosis and senescence, inhibits invasion and enhances chemosensitivity in pancreatic cancer cells

Zhao

Cui

et al. 2011

Gene Ther

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The NAD+-dependent deacetylase, sirtuin 1 (SIRT1), has been recently been suspected to have a role in tumorigenesis. We investigated the expression of SIRT1 in pancreatic cancer and the effect of SIRT1-targeted RNA interference (RNAi) on cell proliferation and tumor formation in a pancreatic cancer cell line, PANC1. The expression of SIRT1 was investigated in 49 specimens of pancreatic cancer and adjacent normal pancreatic tissues. SIRT1 was overexpressed in pancreatic cancer tissues at both the mRNA and protein levels, with increased SIRT1 positivity associated with tumors from patients over 60 years old, tumors larger than 4 cm, higher TNM (extent of tumor (T), the extent of spread to lymph nodes (N), and presence of distant metastasis (M)) stage or the presence of lymph node or hepatic metastases. The PANC-1 was stably transfected with a SIRT1 small hairpin RNA (shRNA) expression plasmid and compared with untransfected and PANC-1-negative RNAi cells. Proliferation of PANC-1-SIRT1-RNAi cells was significantly reduced, accompanied by increased rates of apoptosis, G1 arrest and senescence. Furthermore, FOXO3a expression was markedly upregulated in PANC-1-SIRT1-RNAi cells, but no significant difference in p53 expression was observed. The invasive ability of PANC-1-SIRT1-RNAi cells was markedly reduced in vitro, which was linked to increased E-cadherin and reduced-MMP expression. Additionally, PANC-1-SIRT1-RNAi cells had a significantly reduced capacity to form tumors in vivo compared with untransfected and PANC-1-negative RNAi cells. These results suggest that SIRT1 may promote cell proliferation and tumor formation in pancreatic cancer, and downregulation of SIRT1 using shRNA could provide a novel therapeutic treatment. Gene Therapy (2011) 18, 920-928; doi:10.1038/gt.2011.81; published online 16 June 2011Keywords: SIRT1; RNAi; pancreatic cancer; proliferation; apoptosis INTRODUCTION Pancreatic cancer is one of the most aggressive solid malignancies, the third most common gastrointestinal malignancy, the fifth leading cause of cancer mortality and is a leading cause of cancer-related deaths in the developed world. 1 One key characteristic of pancreatic cancer is early systemic metastasis and extremely rapid local tumor progression. 2 Resistance to existing chemotherapeutic agents occurs commonly in pancreatic cancer therapy, 3 and therefore, there is an urgent need to elucidate the molecular mechanisms that underlie the malignant behavior of pancreatic cancer.It has been recently suspected that sirtuin 1 (SIRT1) is involved in tumorigenesis. 4,5 SIRT1 is one of seven members of the sirtuin family of nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylases, with sequence homology to the enzymatic domain of yeast silent information regulator 2 (sir2). 6,7 SIRT1 has a large number of histone and non-histone substrates, which are involved in the regulation of metabolism, differentiation, proliferation, senescence, protein degradation and apoptosis. 8 Overexpression of SIRT1 provides a cell su...

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“…The loss of E-cadherin expression in the primary tumor, especially occurring in diffuse type gastric carcinoma [45], might be a possible explanation for this finding as it leads to decreased intercellular adhesion and correlates with tumor cell dissociation [46]. A higher probability for mi and ITC in diffuse histologic type was also reported by other authors [6,10,11,17,45] leading to the conclusion that LN immunohistostaining is of special importance for this cancer entity. Furthermore, positive correlation between LN mi and total gastrectomy was observed in this study, possibly because total gastrectomy led to a significantly higher number of dissected LN in comparison to patients, who received only partial gastric resection (88.5 % of patients with total gastrectomy had more than 15 LN removed versus 67.6 % of patients with distal gastric resection).…”

Section: Survival Analysismentioning

confidence: 57%

“…Immunohistochemistry is a frequently described method to detect ITC and mi not visible in routinely performed haematoxylin and eosin (HE) stain [6,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Besides immunohistostaining serial sectioning and molecular methods are options to improve the accuracy of pathologic examination.…”

Section: Introductionmentioning

confidence: 99%

Gastric carcinoma: stage migration by immunohistochemically detected lymph node micrometastases

Jeuck

Wittekind

2014

Gastric Cancer

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Background Immunohistochemically detected micrometastases of the regional lymph nodes in previously pN0-classified gastric cancer have been incorporated in the TNM staging system. This study aims to determine the incidence of such micrometastases in gastric carcinoma and to investigate their impact on stage grouping and prognosis. Methods Ninety-five patients with gastric carcinoma classified as pN0 by conventional histological examination were enrolled. All patients underwent gastric resection with regional lymphadenectomy between 2006 and 2010. A total of 2018 lymph nodes was obtained (median, 20 Lymph nodes) and immunohistostained with anti-pan cytokeratin antibody (KL1). Results Micrometastases were detected in regional lymph nodes by immunohistostaining in 16 out of all 95 patients. Fourteen patients were upstaged by micrometastasis-positive regional lymph nodes. Three patients demonstrated lymph nodes with isolated tumor cells alone. A significantly higher incidence of micrometastases was observed in patients with diffuse histologic type (p = 0.007) and total gastrectomy (p = 0.007). When isolated tumor cells were also regarded as lymph node involvement, the recurrence rate was significantly higher for node-positive than for node-negative patients and for those younger than 70 years (33.3 and 6.7 %, respectively; p = 0.026; n = 39). Overall survival analysis revealed no significant difference between micrometastasis-positive and micrometastasis-negative patients. ConclusionImmunohistostaining of regional lymph nodes in node-negative gastric carcinoma patients leads to an increased detection of micrometastases with significant implications for the staging system. Although no impact on survival time was shown, the higher recurrence rate for node-positive patients younger than 70 years indicates a prognostic value of immunohistochemically detectable micrometastases.

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The significances of lymph node micrometastasis and its correlation with E‐cadherin expression in pT1‐T3N0 gastric adenocarcinoma

Abstract: Lymph node MM in histologically node-negative gastric cancer was significantly correlated with poor 5-year survival rate. The determination of E-cadherin expression in primary gastric tumor may be useful in prediction of the MM.

Cited by 55 publications

References 24 publications

Cadherin-17 induces tumorigenesis and lymphatic metastasis in gastric cancer through activation of NFκB signaling pathway

Cadherin-17 induces tumorigenesis and lymphatic metastasis in gastric cancer through activation of NFκB signaling pathway

SIRT1 RNAi knockdown induces apoptosis and senescence, inhibits invasion and enhances chemosensitivity in pancreatic cancer cells

Gastric carcinoma: stage migration by immunohistochemically detected lymph node micrometastases

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