Proposal of a Dukes-Mac-Like Staging System for Gastric Cancer

Gurzu, Simona; Sugimura, Haruhiko; Orłowska, Janina; Szederjesi, János; Szentirmay, Zoltán; Bara, Tivadar; Fetyko, Ananmaria; Jung, Ioan

doi:10.1136/jim-2016-000270

Cited by 14 publications

(17 citation statements)

References 13 publications

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“…As overall survival varies in patients with GC within the same stage, the most recent papers have shown that the currently used TNM staging system is not sufficient for prognosis estimation[ 1 ]. The present study confirmed the utility of the newest Dukes-MAC-like staging system[ 9 ], for a proper estimation of long-time survival, and confirmed the independent prognostic role of IHC expression of Maspin and p53, in patients with GC. Despite the intention of including new biomarkers with prognostic potential, the depth of invasion, combined with lymph node status (pTN stage) remain the strongest predictors of outcome in patients with GC[ 8 , 11 ].…”

Section: Discussionsupporting

confidence: 85%

“…The second system used for tumor staging was proposed by our team in 2017 and is called the Dukes-MAC-like staging system[ 9 ]. This system consists of the classification of GCs, based on the depth of invasion (T) and lymph node status (N), in eight groups, as follows: 1-T1N0; 2-T1N1-3; 3-T2N0; 4-T2N1-3; 5-T3N0; 6-T3N1-3; 7-T4N0; 8-T4N1-3[ 9 ].…”

Section: Methodsmentioning

confidence: 99%

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Maspin subcellular expression in wild-type and mutant TP53 gastric cancers

Gurzu¹,

Jung²,

Sugimura³

et al. 2020

WJGO

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BACKGROUND Although the role of p53 in the evolution and prognosis of gastric cancer (GC) has been extensively examined, the exact mechanism of action is incompletely understood. In the last years, p53-target genes were supposed to be involved in the p53 pathway. One of them is the tumor-suppressor gene Maspin, which codifies the protein with the same name. Maspin activity depends on its subcellular localization. To our knowledge, the possible role of TP53 gene in Maspin subcellular localization, in GC cells, has not yet been studied in a large number of human samples. AIM To evaluate the possible role of wild-type and mutated p53 in Maspin subcellular localization. METHODS The present study included 266 consecutive patients with GC in which TP53 gene status, and mutations in exons 2 to 11, respectively, were analyzed and correlated with immunohistochemical expression of p53 and Maspin. RESULTS None of the 266 cases showed mutations in exon 9. The rate of TP53 mutations was 33.83%. The mutation rate was slightly higher in distally-located GCs, with a lower degree (≤ 5 buds/ high power fields) of dyscohesivity ( P < 0.01). The wild-type cases had a longer survival, compared with mutant GCs, especially in patients without lymph node metastases, despite the high depth of tumor infiltration ( P = 0.01). The Dukes-MAC-like staging system was proved to have the most significant independent prognostic value ( P < 0.01). The statistical correlations proved that TP53 gene mutations in exon 7 might induce knockdown of Maspin, but wild-type p53 can partially restore nuclear Maspin expression and decrease the metastatic potential of gastric adenocarcinoma cells. CONCLUSION Downregulated Maspin might be induced by mutations in exon 7 of the TP53 gene but wild-type p53 can partially restore nuclear Maspin expression. These findings should be proved in experimental studies.

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Section: Discussionsupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Maspin subcellular expression in wild-type and mutant TP53 gastric cancers

Gurzu¹,

Jung²,

Sugimura³

et al. 2020

WJGO

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“…[ 3 , 16 , 17 ] In addition, LNR was first carried out by Nitti D, et al as a significant independent prognostic factor in gastric cancer. [ 18 ] Except pN and LNR, LODDS as the log of the ratio between the number of positive and negative lymph nodes [ 19 ] and Dukes-MAC-like pTN staging system [ 20 ] were also shown as strong prognostic indicators in gastric cancer. However, many outcomes of latest researches have confirmed LNR's value and considered it could be better than other lymph node related parameters to predict prognosis because it is less affected by the the extent of lymphadenectomy and the accuracy of positive lymph nodes number detected by pathologists.…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of lymph node ratio for local advanced gastric cancer patients with adjuvant chemoradiotherapy after D2 gastrectomy

Hu¹,

Zhang²,

Yang³

et al. 2018

Medicine

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This study aimed to find the prognostic factors of local advanced gastric cancer patients with adjuvant concurrent chemoradiotherapy after radical D2 gastrectomy, and explore the prognostic value of lymph node ratio (LNR).We retrospectively analyzed 164 gastric cancer patients enrolled in West China Hospital from 2006 to 2013, who underwent D2 radical gastrectomy and adjuvant chemoradiotherapy. With univariate analysis and the Cox regression model, we evaluated the association of LNR and other clinical pathological characteristics with overall survival (OS) and relapse-free survival (RFS) of patients.Of 164 gastric cancer patients, the median age at diagnosis was 60 (IQR 51–66), with 121 males (73.78%) and 43 females (26.22%). The median follow-up time was 41.5 months. One-year and 3-year OS rate of the whole cohort was 97.6% and 88.4%, with 1-year RFS rate of 90.2% and 3-year RFS rate of 76.8%, respectively. In the univariate analysis, we found that age >60years (P = .025), TNM stage III (P = .014), LNR >0.25 (P = .006) and radiation dose <45Gy (P = .048) predicted worse OS. Further multivariate analysis indicated that age >60y (HR 2.375, 95% CI 1.100–5.128; P = .028), TNM stage III (HR 7.692, 95% CI 1.009–58.824; P = .049) and LNR >0.25 (HR 2.439, 95% CI 1.075–5.525; P = .033) were independent prognostic factors for unfavorable OS. The COX analysis showed that related prognostic factors of worse RFS were TNM stage III (HR 3.802, 95% CI 1.506–9.615; P = .049) and LNR >0.25 (HR 2.326, 95% CI 1.332–4.065; P = .003).LNR can be used as an important prognostic indicator for gastric cancer patients with D2 resection and adjuvant chemoradiotherapy, and LNR more than 0.25 indicates poor prognosis.

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“…We aimed to establish the staging according to the most recent edition of the American Joint Committee on Cancer tumor staging manual [ 11 ]. Tumors were also staged according to the Dukes-MAC-like staging system, proposed in 2017 [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

HER2 Heterogeneity in Gastric Cancer: A Comparative Study, Using Two Commercial Antibodies

Satala

Jung

Staden

et al. 2020

Journal of Oncology

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Background. Although amplification of the gene encoding human epidermal growth factor receptor 2 (HER2) is used as an indicator for response to trastuzumab, the reported response rate is low, and few patients with gastric cancer (GC) benefit from this individualized therapy. The aim of this study was to examine the expression of c-erbB-2 oncoprotein (HER2), in GC samples, using two commercial immunohistochemical (IHC) antibodies, and to validate the results by checking HER2 gene amplification by fluorescence in situ hybridization (FISH). Methods. We assessed the IHC expression of HER2 using the polyclonal antibody from Dako and CB11 clone from Leica, in 93 consecutive cases of GC samples. In all of the cases, FISH analysis was also performed using the BOND-MAX platform. Results. No significant difference was observed between the two HER2 antibodies. Of the 93 cases, 22.58% demonstrated at least focal and 1+ HER2 positivity. Seven cases (7.53%) exhibited 3+ expression, and another 7 carcinomas (7.53%) were equivocal (2+). HER2 amplification was seen in 11 cases (11.83%), 10 of which were differentiated adenocarcinomas. In 5 of the cases, 2–5 sections were examined, which proved the extremely high intratumorally/intraglandular heterogeneity. FISH heterogeneity was higher in cases with only 2+ positivity on IHC assessment, compared with those showing at least one small focus of 3+ overexpression. HER2 amplification proved to be an independent negative prognostic factor. Conclusions. Due to the highly heterogeneous aspect of GC, at least 3-4 slides should be assessed by IHC, before considering a tumor to be HER2-negative. In cases with small 3+ foci representing less than 5% of tumor and in equivocal (2+) cases, FISH analysis remains the gold standard method.

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Proposal of a Dukes-Mac-Like Staging System for Gastric Cancer

Cited by 14 publications

References 13 publications

Maspin subcellular expression in wild-type and mutant TP53 gastric cancers

Maspin subcellular expression in wild-type and mutant TP53 gastric cancers

The prognostic value of lymph node ratio for local advanced gastric cancer patients with adjuvant chemoradiotherapy after D2 gastrectomy

HER2 Heterogeneity in Gastric Cancer: A Comparative Study, Using Two Commercial Antibodies

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