TITLE: �From Lauren�s diffuse gastric cancer to WHO�s poorly cohesive carcinoma.� Clinicopathological and prognostic characteristics

Lasarte, Aingeru Sarriugarte; Alberdi, Eva GarcÍa; Indart, Lorea Martinez; Grijalba, Oihane Gutierrez; Abad, Irene Albarez; Lerma, Mikel Guerra; Baraja, Miguel Calle; Alonso, Alberto

doi:10.17235/reed.2020.7184/2020

Cited by 7 publications

(7 citation statements)

References 15 publications

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“…[27] Some studies have shown that compared with intestinal type of gastric cancer, diffuse type has a poor prognosis, and Lauren classification can be used as a marker of prognosis for patients with gastric cancer after radical resection. [28][29][30] This study also shows that Lauren type is an independent risk factor for prognosis of gastric cancer. Tumor deposit, also known as soft tissue extranodal metastases, are defined the presence of tumor cells in the extramural soft tissue of the stomach that is not contiguous with either the tumor primary or the regional lymph nodes.…”

Section: Discussionsupporting

confidence: 64%

Family history of malignant tumor is a predictor of gastric cancer prognosis: Incorporation into a nomogram

et al. 2022

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The purpose of this study was to investigate the impact of a family history of malignant tumor on the prognosis of patients with gastric cancer and develop a nomogram that incorporates a family history of malignant tumor to predict overall survival (OS) in patients with gastric cancer to aid clinicians and patients in decision making. Four hundred eighty-eight patients with gastric cancer undergoing radical gastrectomy in our center were included and randomly split into a training set (n = 350) and a validation set (n = 138) at a ratio of 7:3. Cox univariate regression analysis was used to evaluate the influence of clinicopathological characteristics and family history of malignant tumors on their prognosis, and variables were screened by multivariate Cox regression analysis and consensus on clinical evidence. A nomogram was constructed for OS based on the filtered variables, and the C-index, receiver operating characteristic curve (ROC curve), and calibration curve were used to validate the nomogram and decision curve analysis curve (DCA curve) was used for clinical practicality assessment. Six variables related to OS, including the pathological differentiation degree, Lauren type, infiltration depth, lymph node metastasis, tumor deposit, and family history of malignant tumor, were screened to construct a nomogram. The nomogram developed in this study performed well in the training set and the validation set, with C-index of 0.776 and 0.757, and the area under the ROC curve(AUC) for predicting 1-, 3-, and 5-year survival rates are 0.838, 0.850, 0.820 and 0.754, 0.789, 0.808, respectively. The calibration curve shows that the estimated death risk of the nomogram in the 2 data sets is very close to the actual death risk. The net benefits of nomogramguided prediction of patient survival at 1-, 3-, and 5 years were demonstrated by the DCA curves, which showed high clinical practicability. Family history of malignant tumors is an independent risk factor affecting the prognosis of patients with gastric cancer. The nomogram developed in this research can be used as an important tool to predict the prognosis of gastric cancer patients with family history data.Abbreviations: AIC = Akaike information criterion, AJCC = American Joint Committee on Cancer, ASCO = American Society of Clinical Oncology, AUC = area under the ROC curve, DCA curve = decision curve analysis curve, EM = extranodal metastases, FGC = Family history of gastric cancer, OS = overall survival, ROC curve = receiver operating characteristic curve, WHO = World Health Organization.

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Section: Discussionsupporting

confidence: 64%

Family history of malignant tumor is a predictor of gastric cancer prognosis: Incorporation into a nomogram

et al. 2022

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“…SRC gastric accounts for approximately 3.4% to 50% of gastric cancer cases. 5 , 7 , 8 SRCs have a small nucleus on one side and a cytoplasm that is full of mucus and rarely form lines or coronary structures. The prognosis of SRC gastric cancer is different in early and advanced stages.…”

Section: Introductionmentioning

confidence: 99%

PHLPP1 Overexpression was Associated With a Good Prognosis With Decreased AKT Activity in Gastric Cancer

Park

Jeong

Jung

et al. 2022

Technol Cancer Res Treat

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Introduction: The aim of this study was to perform a clinicopathologic analysis of PHLPP1 expression in gastric cancer patients and analyze AKT activity with chemotherapy drug treatment in cancer subtypes. Materials and Methods: Surgically resected gastric cancer tissue specimens were obtained from 309 patients who underwent gastrectomy, and PHLPP1 expression was validated by tissue microarray analysis with immunohistochemistry. We assessed whether PHLPP1 selectively dephosphorylates Ser473 of AKT in an in-vitro study. Results: We found that the PHLPP1 overexpression (OE) group showed significantly greater proportions of differentiated subtype samples and early T stage samples, lower lymph node metastasis, and lower TNM stage than the PHLPP1 underexpression (UE) group. The overall survival of the PHLPP1-OE group was significantly higher (53.39 ± 0.96 months) than that of the PHLPP1-UE group (47.82 ± 2.57 months) ( P = .01). In vitro analysis, we found that the PHLPP1-OE group showed a significant decrease in relative AKT S-473 levels in both cell lines (MKN-74 and KATO-III). We found that treatment with chemotherapy drugs decreased the activity of Ser473 in the MKN-74 cell line with PHLPP1 OE, but it did not affect the activity of Ser473 in KATO-III cells. Conclusion: We found that patients who overexpressed PHLPP1 showed low recurrence and good prognosis. PHLPP1 was found to work by lowering the activity of AKT Ser473 in gastric cancer. Additionally, we found a clue regarding the mechanism of chemotherapeutic drug resistance in a cell line of signet ring cell origin and will uncover this mechanism in the future.

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“…Compared to other GC subtypes, PC GC is poorly differentiated and easy to metastasized. None of current treatments, including chemotherapy, radiotherapy, targeted therapy and immunotherapy, has shown good results [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Although the histopathological classifications currently remain the most commonly used for therapy decision making in the clinical setting, molecular classifications have been developed to guide future treatment development [ 5 ]. Several different molecular GC classification systems have been proposed these years, attempting to relate molecular features to histological phenotypes and clinical features [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

FGFR2 alteration as a potential therapeutic target in poorly cohesive gastric carcinoma

et al. 2021

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Background Poorly cohesive (PC) is a unique histologic subtype of gastric cancer (GC), with an increasing incidence in recent years. However, the molecular characteristics and therapeutic targets of PC GC are not yet well studied and there are no effective therapies for these patients. Methods Formalin fixed paraffin embedded (FFPE) samples of 556 GC patients, including 64 PC GC, were collected for next-generation sequencing (NGS). Clinical characteristics and genomic profiling were analyzed. FGFR2 expression was detected by quantitative real time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). FGFR2 inhibitors response was studied in vitro. Results Among 556 GC patients, PC GC patients were younger (P = 0.004), had lower tumor mutation burden (TMB-L) (P = 0.001) than non-PC GC. The top 10 most frequently mutated genes in PC GC were TP53 (48%), CDH1 (31%), ARID1A (14%), FGFR2 (14%), ERBB2 (9%), CDKN2A (9%), FGF3 (8%), LRP1B (9%), FGF19 (8%) and FGF4 (8%). Noticeably, FGFR2 is more frequently mutated than non-PC GC (14% vs. 6%, P = 0.037), including copy number variants (CNVs, 12.5%) and gene rearrangements (3.1%, FGFR2/VTI1A and FGFR2/TACC2). Former studies have confirmed that gain of copy number could increase FGFR2 expression and sensitivity to FGFR2 inhibitors in GC. However, no research has verified the function of FGFR2 rearrangements in GC. Our results showed that cell lines of GC transfected with TACC2-FGFR2 fusion had increased mRNA and protein expression of FGFR2, and were more sensitive to FGFR2 inhibitors. FGFR2 inhibitors might be a new therapeutic target for PC GC. In addition, we found patients of PC GC harboring gene rearrangements (n = 9) had poorer overall survival (OS) in comparison with patients without any gene rearrangement (n = 19) (16.0 months vs 21.0 months, P = 0.043). Gene rearrangement might be an adverse prognostic factor for PC GC patients. Conclusions FGFR2 alterations were recurrent in PC GC and FGFR2 inhibitors might be a new therapeutic target for PC GC.

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TITLE: �From Lauren�s diffuse gastric cancer to WHO�s poorly cohesive carcinoma.� Clinicopathological and prognostic characteristics

Cited by 7 publications

References 15 publications

Family history of malignant tumor is a predictor of gastric cancer prognosis: Incorporation into a nomogram

Family history of malignant tumor is a predictor of gastric cancer prognosis: Incorporation into a nomogram

PHLPP1 Overexpression was Associated With a Good Prognosis With Decreased AKT Activity in Gastric Cancer

FGFR2 alteration as a potential therapeutic target in poorly cohesive gastric carcinoma

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