• Chemotherapy
• Endoscopy
• Guidelines
• Stomach neoplasms
• Surgery

• Stomach Neoplasms/therapy
• Stomach Neoplasms/diagnosis
• Humans
• Republic of Korea/epidemiology
• Evidence-Based Medicine/standards

• NCC-2112570 National Cancer Center

• Chemotherapy
• Drug release
• Encapsulation
• Gastrointestinal cancer
• PLGA nanoparticles

• Gastric cancer
• Mucinous gastric carcinoma
• Nomogram
• Prognosis

• Humans
• Retrospective Studies
• Stomach Neoplasms/pathology
• Adenocarcinoma, Mucinous
• Neoplasm Staging
• Neoplasm Invasiveness/pathology
• Prognosis
• Adenocarcinoma/surgery
• Carcinoma, Signet Ring Cell/surgery
• Carcinoma, Signet Ring Cell/pathology

• 82074245 National Natural Science Foundation of China
• 81973634 National Natural Science Foundation of China
• 82204828 National Natural Science Foundation of China
• 81502603 National Natural Science Foundation of China
• 2021YFA0910100 National Key R&D Program of China
• 2022M713203 Chinese Postdoctoral Science Foundation
• ZYYCXTD-C-202208 Collaborative Innovation Center for Modern Science and Technology and Industrial Development of Jiangxi Traditional Medicine
• 2022KY114 Medical Science and Technology Project of Zhejiang Province
• WKJ-ZJ-2104 Medical Science and Technology Project of Zhejiang Province
• JBZX-202006 Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer
• HDMY22H160008 Science Natural Science Foundation of Zhejiang Province
• TGY23H160038 Natural Science Foundation of Zhejiang Province
• 2023KY073 Medicine and Health Science Fund of Zhejiang Province

• early diagnosis
• gastric adenocarcinoma
• mucins
• oesophageal adenocarcinoma
• oesophageal squamous cell carcinoma
• oesophago-gastric cancer

• Cd44v6
• Gastric adenocarcinoma
• HA
• Krukenberg tumor
• Molecular diagnosis
• Transcoelomic metastasis

• Female
• Humans
• Krukenberg Tumor/diagnosis
• Krukenberg Tumor/genetics
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics
• Adenocarcinoma/diagnosis
• Adenocarcinoma/genetics
• Biomarkers, Tumor
• Carcinoma
• Ovarian Neoplasms

• case report
• diagnosis
• follow-up
• mucinous adenocarcinoma
• postoperative treatment
• renal parenchyma

• National Natural Science Foundation of China
• West China Hospital, Sichuan University

• Bioinformatics
• Deep learning
• Genomics
• Mucinous gastric carcinoma
• Pathomics

• Chemotherapy
• Endoscopy
• Guidelines
• Stomach neoplasms
• Surgery

• The Korean Gastric Cancer Association
• NCC-2112570-1 Ministry of Health and Welfare
• NCC-2112570-2 Ministry of Health and Welfare
• NCC-2112570-3 Ministry of Health and Welfare

• Gastric cancer
• Genomics
• Microsatellite instability
• Mucinous carcinoma

Mucinous gastric carcinoma (MGC) is a rare histological type of gastric carcinoma. Calcifications, seen on imaging and histopathological preparations, and which are infrequent in other types of gastric carcinoma, are characteristic of MGC. We present a patient with MGC with calcifications of the gastric wall and describe the computerized tomography (CT) features of the lesion and changes in the calcifications before and after chemotherapy.

A 61-year-old man was admitted to our hospital in May 2020 because of a large, tender abdominal mass. Abdominal CT showed diffuse, irregular thickening of the gastric walls, with miliary and punctate calcifications. There were metastases to the perigastric and retroperitoneal lymph nodes and also peritoneal seeding. Histological examination of a specimen obtained by endoscopic biopsy showed poorly differentiated calcified signet-ring cell gastric cancer. The patient was clinically staged with T4N+M1 disease. He was treated with docetaxel, cisplatin, and fluorouracil as first-line therapy, irinotecan combined with S-1 as second-line chemotherapy, and programmed cell death protein 1 as third-line therapy. The patient underwent a total of nine cycles of chemotherapy. Follow-up CT scans every 3 mo showed continually increasing calcifications. As of this writing, the patient has survived almost 1 year.

In this case report, we describe the histopathological and imaging characteristics of a patient with gastric cancer receiving chemotherapy. Multiple punctate calcifications were seen, which gradually increased during chemotherapy. Several possible mechanisms for the calcifications are described, but further research is needed. Future findings may lead to new approaches for the evaluation and treatment of such tumors.

• Gastric cancer
• Calcification
• Computerized tomography
• Chemotherapy
• Prognosis
• Case report

• Gastric carcinoma
• Tumor associated macrophages
• Tumor immune microenvironment
• Tumor infiltrating lymphocytes

• B7-H1 Antigen
• Carcinoma
• Cell Differentiation
• Humans
• Lymphocytes, Tumor-Infiltrating
• Stomach Neoplasms
• Tumor Microenvironment

• Mucins
• Prognosis
• Stomach neoplasms

• brain metastases
• musashi1
• numb
• tumor stem cells

• Adult
• Aged
• Brain/metabolism
• Brain Neoplasms/genetics
• Brain Neoplasms/metabolism
• Brain Neoplasms/secondary
• Case-Control Studies
• Female
• Humans
• Immunohistochemistry
• Male
• Membrane Proteins/genetics
• Membrane Proteins/metabolism
• Middle Aged
• Nerve Tissue Proteins/genetics
• Nerve Tissue Proteins/metabolism
• RNA, Messenger/metabolism
• RNA-Binding Proteins/genetics
• RNA-Binding Proteins/metabolism
• Reverse Transcriptase Polymerase Chain Reaction
• Young Adult

• Histology
• Neuropilin-1
• Prognosis
• Stomach neoplasms
• Survival

• Adenocarcinoma, Mucinous/genetics
• Adenocarcinoma, Mucinous/mortality
• Adenocarcinoma, Mucinous/pathology
• Adult
• Aged
• B7-H1 Antigen/analysis
• CA-19-9 Antigen/blood
• Carcinoembryonic Antigen/blood
• Female
• Humans
• Male
• Middle Aged
• Mutation
• Neoplasm Recurrence, Local
• Propensity Score
• Prospective Studies
• Stomach Neoplasms/genetics
• Stomach Neoplasms/mortality
• Stomach Neoplasms/pathology

Mucinous gastric carcinoma (MGC) is a rare histological subtype of gastric cancer. The clinicopathological characteristics and CT features of MGC remain controversial. This study aimed to determine the clinicopathological characteristics and CT features of MGC. We reviewed 62 patients with MGC and 104 patients with non-mucinous gastric carcinoma (NMGC), pathologically confirmed between 2003 and 2015. There are significant differences in some clinicopathological characteristics and CT features between MGC and NMGC. NMGC occurs preferentially in males and more frequently in the lower third of the stomach. Patients with MGC were characterized by larger tumor size, more advanced tumor stages (II and III) and fewer lymphatic invasions. Layered enhancement (83.3%) was the main pattern of MGC, while the most common pattern in NMGC was homogeneous enhancement (52.6%), followed by heterogonous enhancement (34.6%). The degree of enhancement of the inner layer in MGC was significantly higher than in NMGC (ΔCT of portal venous phase: 54.57 Hu vs. 47.19 Hu, P = 0.034), while the middle or outer layer in MGC was significantly less enhanced (ΔCT of portal venous phase: 19.07 Hu vs. 33.09 Hu, P <0.001). Calcifications were more common in MGC (P <0.001). ROC curves revealed that the most effective variables in distinguishing MGC and NMGC were ΔCT of the middle or outer layer in the arterial phase (AUC=0.774) and portal venous phase (AUC=0.774), followed by the attenuation value of the middle or outer layer in the unenhanced phase (AUC=0.763). Calcifications had a high specificity (98.7%) in the diagnosis of MGC. The accuracy (86.1%), sensitivity (83.3%) and specificity (87.2%) of layered enhancement in diagnosing MGC were all high. Therefore, MGC was more likely to have larger tumor size and more advanced tumor stage (II and III) than NMGC. The thicker gastric wall, layered enhancement pattern and calcification were highly suggestive CT features for differentiating MGC from NMGC.

• clinicopathological characteristics
• computed tomography
• mucinous gastric carcinoma
• non-mucinous gastric carcinoma

The epidemiology of metastatic gastric cancer is unexplored because cancer registries seldom cover metastatic involvement apart from “present or not”. We used a novel approach by utilizing Swedish registers to assess metastatic spread in gastric cancer. To our knowledge, this is the first nationwide description of metastases in gastric cancer.

The most common sites of metastasis were liver (in 48% of metastatic cancer patients), peritoneum (32%), lung (15%), and bone (12%). Metastases to the lung, nervous system, and bone were more frequent in cardia cancer and men, whereas non-cardia cancer more frequently metastasized within the peritoneum. Signet ring adenocarcinomas more frequently metastasized within the peritoneum, bone and ovaries, and less frequently to the lungs and liver compared with generic adenocarcinoma. The liver and the peritoneum were commonly single metastases while lung metastases occurred frequently together with liver metastases. The median survival in metastatic gastric cancer was 3 months, worst among those with bone and liver metastases (2 months).

A total of 7,559 patients with gastric cancer were identified. Metastatic patterns and survival depending on sex, age, stage, anatomical location (cardia and non-cardia), and histological type were assessed.

The patterns of metastasis differ notably depending on histological type. Cardia cancer exhibits a completely different metastatic behavior than non-cardia cancer. Awareness of the differing patterns may guide in tailored diagnosis of metastases. Survivors from cardia cancer would benefit from increased surveillance of extraperitoneal metastases. Bone metastases should be considered in patients with signet ring adenocarcinoma if symptoms emerge.

• epidemiology
• gastric cancer
• metastasis

Metastasis is a complex and well-coordinated phenotypic transformation of cancer cells governed by aberrant genetic and molecular pathways. It has been approved as the most consistent cause of cancer death. With emerging insight into the genomics, transcriptomics and proteomics, progress has been made and reasonably large number of molecular pathways of metastasis has been forwarded, but our understanding of precise underlying molecular mechanisms remains largely scarce. It has been well-known for around a decade and more that platelets are intriguingly contributing to the cancer metastasis. However, it is only recently that cancer cells can activate platelets have started to become apparent. Surprisingly, platelets in response to cancer cell activation, supported by research observations, allow cancer cells to escape immune removal, prolong survival in vascular compartment, increased cellular adhesion and develop new cellular niches which eventually help to favor cancer metastasis. Although a widely acknowledged plausible explanation that cancer cells activate platelets to facilitate in their distant spread, the description of this remains to be confirmed. In recent years, mucins, heavily glycosylated peptide structure, have been introduced to be released by several types of cancer cells. They account for poor prognosis in wide array of malignancies, because of their significant ability to induce metastatic process. The mechanism responsible for their increased metastatic propensity remains uncharacterized, but recent work suggested the role of cancer expressed mucins in initiating platelet thrombus. The association of cancer yield mucins, platelets and metastasis therefore suggests a pressing need to explore novel molecular mechanisms and therapeutic targets thereafter.

• Gastric cancer
• Medical oncology
• Multidetector computed tomography
• Prognosis
• Survival

• Adenocarcinoma/diagnostic imaging
• Adenocarcinoma/pathology
• Adenocarcinoma/surgery
• Aged
• Biomarkers
• Biopsy
• Carcinoma, Signet Ring Cell/diagnostic imaging
• Carcinoma, Signet Ring Cell/pathology
• Carcinoma, Signet Ring Cell/surgery
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multidetector Computed Tomography
• Multivariate Analysis
• Neoplasm Staging
• Prognosis
• Proportional Hazards Models
• Retrospective Studies
• Stomach Neoplasms/diagnostic imaging
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery
• Survival Rate

• microsatellite instability
• neoplasms by histologic type
• stomach neoplasms

• Aged
• DNA Mismatch Repair
• DNA-Binding Proteins/genetics
• DNA-Binding Proteins/metabolism
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Male
• Microsatellite Instability
• Middle Aged
• Mismatch Repair Endonuclease PMS2/genetics
• Mismatch Repair Endonuclease PMS2/metabolism
• MutL Protein Homolog 1/genetics
• MutL Protein Homolog 1/metabolism
• MutS Homolog 2 Protein/genetics
• MutS Homolog 2 Protein/metabolism
• Poland
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Transcriptome/genetics

The clinicopathological characteristics and outcomes of mucinous gastric adenocarcinoma (GC) remain unclear. We report the clinicopathological features and prognosis of patients with mucinous histology who underwent radical-intent gastrectomy.

We reviewed the medical records of 1470 patients with pathologically proven undifferentiated GC undergoing radical-intent gastrectomy between 1995 and 2007. The patients were stratified into three groups according to their histological type: mucinous carcinoma (MC), signet ring cell carcinoma (SRCC), and poorly differentiated carcinoma (PDC). Clinicopathological factors affecting prognosis were collected prospectively and analyzed.

In stage III MC, the age and size were significantly greater and larger than in SRCC and PDC; a lower proportion of perineural invasion was identified in MC, and female predominance was noted in SRCC in comparison with MC and PDC. The cumulative overall survival rates of stage I–III GC patients with MC were significantly superior compared to those with PDC, but not SRCC. Stage III GC patients with MC had a better prognosis than those with SRCC or PDC; the difference in survival was not evident in stages I or II.

Thus, MC presents with different clinicopathological features and prognosis from SRCC and PDC. The patients with stage III gastric MC had favorable outcomes.

• Mucinous gastric cancer
• Prognostic factor
• Undifferentiated

• Gastric carcinoma
• Mucinous carcinoma
• Prognosis
• Signet ring cell carcinoma
• Surgery

• Chemotherapy
• Gastrointestinal cancers
• Mucinous ovarian cancer
• Targeted therapy

• Glycoproteins
• Goblet cells
• Human
• Membrane proteins
• Mucins
• Mucus
• Polymorphism

AIM: To compare characteristics and prognosis of gastric cancer based on age.

METHODS: A retrospective study was conducted on clinical and molecular data from patients (n = 1658) with confirmed cases of gastric cancer in Seoul National University Bundang Hospital (Seoul, South Korea) from 2003 to 2010 after exclusion of patients diagnosed with lymphoma, gastrointestinal stromal tumor, and metastatic cancer in the stomach. DNA was isolated from tumor and adjacent normal tissue, and a set of five markers was amplified by polymerase chain reaction to assess microsatellite instability (MSI). MSI was categorized as high, low, or stable if ≥ 2, 1, or 0 markers, respectively, had changed. Immunohistochemistry was performed on tissue sections to detect levels of expression of p53, human epidermal growth factor receptor (HER)-2, and epidermal growth factor receptor. Statistical analysis of clinical and molecular data was performed to assess prognosis based on the stratification of patients by age (≤ 45 and > 45 years).

RESULTS: Among the 1658 gastric cancer patients, the number of patients with an age ≤ 45 years was 202 (12.2%; 38.9 ± 0.4 years) and the number of patients > 45 years was 1456 (87.8%; 64.1 ± 0.3 years). Analyses revealed that females were predominant in the younger group (P < 0.001). Gastric cancers in the younger patients exhibited more aggressive features and were at a more advanced stage than those in older patients. Precancerous lesions, such as atrophic gastritis and intestinal metaplasia, were observed less frequently in the older than in the younger group (P < 0.001). Molecular characteristics, including overexpression of p53 (P < 0.001), overexpression of HER-2 (P = 0.006), and MSI (P = 0.006), were less frequent in gastric cancer of younger patients. Cancer related mortality was higher in younger patients (P = 0.048), but this difference was not significant after adjusting for the stage of cancer.

CONCLUSION: Gastric cancer is distinguishable between younger and older patients based on both clinicopathologic and molecular features, but stage is the most important predictor of prognosis.

• Age
• Gastric cancer
• Microsatellite instability
• Molecular pathology
• Prognosis
• Stage

• Adult
• Age Factors
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/genetics
• Disease-Free Survival
• Female
• Hospitals, University
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Male
• Microsatellite Instability
• Middle Aged
• Molecular Diagnostic Techniques
• Neoplasm Staging
• Predictive Value of Tests
• Receptor, ErbB-2/analysis
• Republic of Korea
• Retrospective Studies
• Risk Factors
• Stomach Neoplasms/chemistry
• Stomach Neoplasms/genetics
• Stomach Neoplasms/mortality
• Stomach Neoplasms/pathology
• Stomach Neoplasms/therapy
• Time Factors
• Tumor Suppressor Protein p53/analysis

AIM: To analyze predictive factors for lymph node metastasis in early gastric cancer.

METHODS: We analyzed 1104 patients with early gastric cancer (EGC) who underwent a gastrectomy with lymph-node dissection from May 2003 through July 2011. The clinicopathologic factors and molecular markers were assessed as predictors for lymph node metastasis. Molecular markers such as microsatellite instability, human mutL homolog 1, p53, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) were included. The χ² test and logistic regression analysis were used to determine clinicopathologic parameters.

RESULTS: Lymph node metastasis was observed in 104 (9.4%) of 1104 patients. Among 104 cases of lymph node positive patients, 24 patients (3.8%) were mucosal cancers and 80 patients (16.7%) were submucosal. According to histologic evaluation, the number of lymph node metastasis found was 4 (1.7%) for well differentiated tubular adenocarcinoma, 45 (11.3%) for moderately differentiated tubular adenocarcinoma, 36 (14.8%) for poorly differentiated tubular adenocarcinoma, and 19 (8.4%) for signet ring cell carcinoma. Of 690 EGC cases, 77 cases (11.2%) showed EGFR overexpression. HER2 overexpression was present in 110 cases (27.1%) of 406 EGC patients. With multivariate analysis, female gender (OR = 2.281, P = 0.009), presence of lymphovascular invasion (OR = 10.950, P < 0.0001), diameter (≥ 20 mm, OR = 3.173, P = 0.01), and EGFR overexpression (OR = 2.185, P = 0.044) were independent risk factors for lymph node involvement.

CONCLUSION: Female gender, tumor size, lymphovascular invasion and EGFR overexpression were predictive risk factors for lymph node metastasis in EGC.

• Receptor
• Epidermal growth factor
• Stomach neoplasms
• Carcinoma
• Neoplasm metastasis
• Lymph node

• Adenocarcinoma/chemistry
• Adenocarcinoma/diagnosis
• Adenocarcinoma/genetics
• Adenocarcinoma/pathology
• Adenocarcinoma/surgery
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/genetics
• Cell Differentiation
• Chi-Square Distribution
• Early Detection of Cancer/methods
• ErbB Receptors/analysis
• Female
• Gastrectomy
• Humans
• Immunohistochemistry
• Logistic Models
• Lymph Node Excision
• Lymph Nodes/chemistry
• Lymph Nodes/pathology
• Lymph Nodes/surgery
• Lymphatic Metastasis
• Male
• Microsatellite Repeats
• Middle Aged
• Multivariate Analysis
• Neoplasm Invasiveness
• Odds Ratio
• Predictive Value of Tests
• Retrospective Studies
• Risk Factors
• Sex Factors
• Stomach Neoplasms/chemistry
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery
• Tumor Burden
• Up-Regulation

The increasing interest of the oncology community in tumour classification and prediction of outcome to targeted therapies has put emphasis on an improved identification of tumour types. Colorectal mucinous adenocarcinoma (MC) is a subtype that is characterized by the presence of abundant extracellular mucin that comprises at least 50% of the tumour volume and is found in 10–15% of colorectal cancer patients. MC development is poorly understood, however, the distinct clinical and pathological presentation of MC suggests a deviant development and molecular background. In this review we identify common molecular and genetic alterations in colorectal MC. MC is characterized by a high rate of MUC2 expression. Mutation rates in the therapeutically important RAS/RAF/MAPK and PI3K/AKT pathways are significantly higher in MC compared with non‐mucinous adenocarcinoma. Furthermore, mucinous adenocarcinoma shows higher rates of microsatellite instability and is more frequently of the CpG island methylator phenotype. Although the majority of MCs arise from the large intestine, this subtype also develops in other organs, such as the stomach, pancreas, biliary tract, ovary, breast and lung. We compared findings from colorectal MC with tumour characteristics of MCs from other organs. In these organs, MCs show different mutation rates in the RAS/RAF/MAPK and PI3K/AKT pathways as well, but a common mucinous pathway cannot be identified. Identification of conditions and molecular aberrations that are associated with MC generates insight into the aetiology of this subtype and improves understanding of resistance to therapies.

• colorectal carcinoma
• genotype
• molecular pathology
• mucinous carcinoma
• phenotype

Tropomyosin-related receptor kinase B (TrkB) promotes proliferation and invasion, relating to poor prognosis of various malignancies. We examined the role of TrkB at the invasive front of gastric cancer (GC) and its association with tumour cell dedifferentiation and tumour budding.

Immunoreactive TrkB was evaluated at the tumour centre and margin using whole-tissue sections of 320 GC patients. Tumour cell dedifferentiation was defined as higher histologic grade at the tumour margin than the surface or tumour centre. Tumour budding was also scored on cytokeratin-stained sections.

Sixty-five patients (20%) showed higher TrkB expression at the invasive front (TrkB expression was higher at the tumour margin than tumour centre). It was significantly associated with several aggressive phenotypes in the full cohort (n=320). It showed a prognostic significance in test subgroup (n=98) and was identified as an independent prognostic factor (HR=2.09; 95% CI: 1.26–3.53) by multivariate analysis in validation subgroup (n=222). Twenty-one patients showed tumour cell dedifferentiation. In predominantly differentiated tumour, higher TrkB at the invasive front was significantly associated with tumour budding rather than tumour cell dedifferentiation.

Assessment of immunoreactive TrkB at the invasive front by whole-tissue sections provides prognostic information for GC patients.

Pepsinogen C (PGC) and mucin1 (MUC1) are important physiologically functional gastric proteins; Mucin2 (MUC2) is an “ectopic” functional protein in intestinal metaplasia of gastric mucosa. We analyzed the co-expression of the above-mentioned three proteins in dynamic gastric diseases {superficial gastritis (SG)-atrophic gastritis (AG)--gastric cancer (GC)} as well as different histological types of gastric cancer in order to find molecular phenotypes of gastric cancer and precancerous disease and further explore the potential co-function of PGC, MUC1 and MUC2 in the occurrence and development of gastric cancer.

The SG-AG-GC sequence was 57-57-70 cases in this case–control study, respectively. Different histological types of GC were 28 cases of highly and moderately differentiated aden ocarcinoma (HMDA)、30 of poorly differentiated adenocarcinoma (PDA) and 12 of mucinous adenocarcinoma (MA) or signet ring cell carcinoma (SRCC). PGC, MUC1 and MUC2 expression in situ were detected in all 184 cases using immunohistochemistry.

Both PGC and MUC1 had a significantly decreased expression in GC than in SG and AG (P < 0.0001 and P < 0.01, respectively); While MUC2 had a significant increased expression in AG than in SG and GC (P < 0.0001). Seven phenotypes of PGC, MUC1 and MUC2 co-expression were found in which PGC+/MUC1+/MUC2- phenotype took 94.7%(54/57) in SG group; PGC+/MUC1+/MUC2+ and PGC-/MUC1+/MUC2+ phenotype took 43.9% (25/57) and 52.6% (30/57) in AG; the phenotypes in GC group appeared variable; extraordinarily, PGC-/MUC1-/MUC2+ phenotype took 100% (6/6) in MA or SRCC group and had a statistical significance compared with others (P < 0.05).

Phenotypes of PGC, MUC1 and MUC2 co-expression in dynamic gastric diseases are variable. In SG group it always showed PGC+/MUC1+/MUC2- phenotype and AG group showed two phenotypes (PGC+/MUC1+/MUC2+ and PGC-/MUC1+/MUC2+); the phenotypes in GC group appeared variable but the phenotype of PGC-/MUC1-/MUC2+ may be a predictive biomarker for diagnosing MA or SRCC, or distinguishing histological MA or SRCC from tubular adenocarcinoma accompanied by mucinous secretion or signet ring cell scattered distribution.

During specimen processing in surgical pathology laboratories, specimen-related adverse events (SRAEs), such as mislabeling and specimen mixed-up might occur. In these situations, molecular techniques using short tandem repeat (STR) loci are required to identify the personal identity. Microsatellite instability (MSI) test is widely used for screening the hereditary non-polyposis colon cancer (Lynch syndrome) in surgical pathologies using polymorphic STR markers. We tried to evaluate the applicability of the MSI test for SRAEs.

We obtained 253 MSI test results to analyze the allele frequencies. After calibrating the estimated nucleotide lengths, we calculated the allele frequencies, a random match probability, and a likelihood ratio (LR) of three dinucleotide STR markers (D5S349, D17S250, and D2S123).

The distribution of LR was 136.38 to 5,606,213.10. There was no case of LR<100. In addition, there were 153 cases (60.5%) of LR ranging from 100 to 10,000 and 100 cases (39.5%) of LR>10,000. Furthermore, the combined probability of identity was 9.23×10^-4 and the combined power of exclusion was 0.99908.

Using the three STR markers that are recommended for MSI test, all the cases were positively identified in 1% range and about one-third cases showed high LR (>10,000). These results showed that MSI tests are useful to screen the personal identity in case of SRAE in pathology laboratories.

• Biometric identification
• Gene frequency
• Microsatellite instability
• Microsatellite repeats

AIM: To test the efficiency of a recently proposed histotype-based grading system in a consecutive series of gastric cancers.

METHODS: Two hundred advanced gastric cancers operated upon in 1980-1987 and followed for a median 159 mo were investigated on hematoxylin-eosin-stained sections to identify low-grade [muconodular, well differentiated tubular, diffuse desmoplastic and high lymphoid response (HLR)], high-grade (anaplastic and mucinous invasive) and intermediate-grade (ordinary cohesive, diffuse and mucinous) cancers, in parallel with a previously investigated series of 292 cases. In addition, immunohistochemical analyses for CD8, CD11 and HLA-DR antigens, pancytokeratin and podoplanin, as well as immunohistochemical and molecular tests for microsatellite DNA instability and in situ hybridization for the Epstein-Barr virus (EBV) EBER1 gene were performed. Patient survival was assessed with death rates per 100 person-years and with Kaplan-Meier or Cox model estimates.

RESULTS: Collectively, the four low-grade histotypes accounted for 22% and the two high-grade histotypes for 7% of the consecutive cancers investigated, while the remaining 71% of cases were intermediate-grade cancers, with highly significant, stage-independent, survival differences among the three tumor grades (P = 0.004 for grade 1 vs 2 and P = 0.0019 for grade 2 vs grade 3), thus confirming the results in the original series. A combined analysis of 492 cases showed an improved prognostic value of histotype-based grading compared with the Lauren classification. In addition, it allowed better characterization of rare histotypes, particularly the three subsets of prognostically different mucinous neoplasms, of which 10 ordinary mucinous cancers showed stage-inclusive survival worse than that of 20 muconodular (P = 0.037) and better than that of 21 high-grade (P < 0.001) cases. Tumors with high-level microsatellite DNA instability (MSI-H) or EBV infection, together with a third subset negative for both conditions, formed the T8 cell-rich HLR group, the largest group among low-grade histotypes. Coexisting HLR proved to be a factor in improved prognosis in tumors with microsatellite instability (P = 0.0015 vs HLR-/MSI-H tumors) or DR type human leukocyte antigen expression (P = 0.033 vs HLR^-/HLA-DR⁺ tumors).

CONCLUSION: Identification of low- and high-grade histotypes can improve the prognostic assessment of a substantial proportion of gastric cancers in routine diagnostic practice.

• Gastric cancer
• High-grade histotype
• Low-grade histotype
• Lymphoid response
• Epstein-Barr virus
• Microsatellite instability

• mucins
• cancer therapy
• cancer diagnosis

• Animals
• Antibodies/therapeutic use
• Biomarkers/metabolism
• Humans
• Models, Biological
• Mucins/immunology
• Mucins/metabolism
• Neoplasms/diagnosis
• Neoplasms/drug therapy
• Neoplasms/therapy

• U01 CA111294 NCI NIH HHS
• R01 CA131944-02 NCI NIH HHS
• CA133774 NCI NIH HHS
• R01 CA078590 NCI NIH HHS
• R01 CA133774 NCI NIH HHS
• UO1 CA111294 NCI NIH HHS
• CA131944 NCI NIH HHS
• R01 CA131944 NCI NIH HHS
• CA78590 NCI NIH HHS