The clinicopathological and molecular features of sporadic gastric foveolar type neoplasia

Abstract Background: Crawling-type adenocarcinoma (CRA) is an important gastric cancer (GC) subtype that exhibits a specific histological pattern and has characteristic clinicopathological findings. Despite its characteristic histology, little is known about the molecular characteristics of CRA. Methods: We examined 254 GC cases, including 51 cases of CRA and 126 cases having conventional differentiated adenocarcinomas (CDAs). Results for immunohistochemistry (mucin phenotype; Muc5AC, Muc6, Muc2 and CD10, CDX-2, MLH-1 and β-catenin), mutation analysis ( TP53 , KRAS and BRAF ), microsatellite instability (BAT25, BAT26, D2S123, D5S346 and D17S250), DNA methylation status by a two-panel method ( RUNX3 , MINT31 , LOX, NEUROG1 , ELMO1 and THBD ), MLH-1 promoter methylation, and allelic imbalance (AI; 1p, 3p, 4p, 5q, 8p, 9p, 13q, TP53, 18q and 22q) were examined. Results: CRAs were more likely to occur in the middle third of the stomach, in younger patients and to be macroscopically depressed. Nuclear accumulation of β-catenin and loss of MLH-1 expression were less frequent among CRA cases compared to CDA cases. At a molecular level, CRA is often characterized by the deletion mutation c.529_546 (18-base pair deletion at codon 177-182 in exon 5), in the TP53 gene (10 cases). Although the low methylation epigenotype was significantly more frequent for CRAs compared to CDAs, multiple AIs were more often seen in CRAs relative to CDAs. Conclusions: The results demonstrated that TP53 mutations, particularly c.529_546del, and multiple AIs are closely associated with CRA carcinogenesis. Our results suggest that CRA is an independent entity of GC in terms of clinicopathologic and molecular findings.

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Analysis of clinicopathological and molecular features of crawling-type gastric adenocarcinoma

10.21203/rs.3.rs-37904/v4 ◽

2020 ◽

Author(s):

Yasuko Fujita ◽

Noriyuki Uesugi ◽

Ryo Sugimoto ◽

Makoto Eizuka ◽

Yosuke Toya ◽

...

Keyword(s):

Allelic Imbalance ◽

Molecular Level ◽

Methylation Status ◽

Nuclear Accumulation ◽

Molecular Characteristics ◽

Mucin Phenotype ◽

Molecular Features ◽

Base Pair Deletion ◽

Clinicopathological Findings ◽

Independent Entity

Abstract Background: Crawling-type adenocarcinoma (CRA) is an important gastric cancer (GC) subtype that exhibits a specific histological pattern and has characteristic clinicopathological findings. Despite its characteristic histology, little is known about the molecular characteristics of CRA. Methods: We examined 254 GC cases, including 51 cases of CRA and 126 cases having conventional differentiated adenocarcinomas (CDAs). Results for immunohistochemistry (mucin phenotype; Muc5AC, Muc6, Muc2 and CD10, CDX-2, MLH-1, p53 and β-catenin), mutation analysis (TP53, KRAS and BRAF), microsatellite instability (BAT25, BAT26, D2S123, D5S346 and D17S250), DNA methylation status by a two-panel method (RUNX3, MINT31, LOX, NEUROG1, ELMO1 and THBD), MLH-1 promoter methylation, and allelic imbalance (AI; 1p, 3p, 4p, 5q, 8p, 9p, 13q, TP53, 18q and 22q) were examined. Results: CRAs were more likely to occur in the middle third of the stomach, in younger patients and to be macroscopically depressed. Nuclear accumulation of β-catenin and loss of MLH-1 expression were less frequent among CRA cases compared to CDA cases. At a molecular level, CRA is often characterized by the deletion mutation c.529_546 (18-base pair deletion at codon 177-182 in exon 5) in the TP53 gene (10 cases). Although the low methylation epigenotype was significantly more frequent for CRAs compared to CDAs, multiple AIs were more often seen in CRAs relative to CDAs. Conclusions: The results demonstrated that TP53 mutations, particularly c.529_546del, and multiple AIs are closely associated with CRA carcinogenesis. Our results suggest that CRA is an independent entity of GC in terms of clinicopathologic and molecular findings.

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Analysis of clinicopathological and molecular features of crawling-type gastric adenocarcinoma

10.21203/rs.3.rs-37904/v3 ◽

2020 ◽

Author(s):

Yasuko Fujita ◽

Noriyuki Uesugi ◽

Ryo Sugimoto ◽

Makoto Eizuka ◽

Yosuke Toya ◽

...

Keyword(s):

Allelic Imbalance ◽

Methylation Status ◽

Tp53 Gene ◽

Nuclear Accumulation ◽

Molecular Characteristics ◽

Mucin Phenotype ◽

Molecular Features ◽

Base Pair Deletion ◽

Clinicopathological Findings ◽

Independent Entity

Abstract Background: Crawling-type adenocarcinoma (CRA) is an important gastric cancer (GC) subtype that exhibits a specific histological pattern and has characteristic clinicopathological findings. Despite its characteristic histology, little is known about the molecular characteristics of CRA. Methods: We examined 254 GC cases, including 51 cases of CRA and 126 cases having conventional differentiated adenocarcinomas (CDAs). Results for immunohistochemistry (mucin phenotype; Muc5AC, Muc6, Muc2 and CD10, CDX-2, MLH-1 and β-catenin), mutation analysis ( TP53 , KRAS and BRAF ), microsatellite instability (BAT25, BAT26, D2S123, D5S346 and D17S250), DNA methylation status by a two-panel method ( RUNX3 , MINT31 , LOX, NEUROG1 , ELMO1 and THBD ), MLH-1 promoter methylation, and allelic imbalance (AI; 1p, 3p, 4p, 5q, 8p, 9p, 13q, TP53, 18q and 22q) were examined. Results: CRAs were more likely to occur in the middle third of the stomach, in younger patients and to be macroscopically depressed. Nuclear accumulation of β-catenin and loss of MLH-1 expression were less frequent among CRA cases compared to CDA cases. At a molecular level, CRA is often characterized by the deletion mutation c.529_546 (18-base pair deletion at codon 177-182 in exon 5), in the TP53 gene (10 cases). Although the low methylation epigenotype was significantly more frequent for CRAs compared to CDAs, multiple AIs were more often seen in CRAs relative to CDAs. Conclusions: The results demonstrated that TP53 mutations, particularly c.529_546del, and multiple AIs are closely associated with CRA carcinogenesis. Our results suggest that CRA is an independent entity of GC in terms of clinicopathologic and molecular findings.

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Analysis of clinicopathological and molecular features of crawling-type gastric adenocarcinoma

Diagnostic Pathology ◽

10.1186/s13000-020-01026-7 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Yasuko Fujita ◽

Noriyuki Uesugi ◽

Ryo Sugimoto ◽

Makoto Eizuka ◽

Yosuke Toya ◽

...

Keyword(s):

Allelic Imbalance ◽

Molecular Level ◽

Methylation Status ◽

Nuclear Accumulation ◽

Molecular Characteristics ◽

Mucin Phenotype ◽

Molecular Features ◽

Base Pair Deletion ◽

Clinicopathological Findings ◽

Independent Entity

Abstract Background Crawling-type adenocarcinoma (CRA) is an important gastric cancer (GC) subtype that exhibits a specific histological pattern and has characteristic clinicopathological findings. Despite its characteristic histology, little is known about the molecular characteristics of CRA. Methods We examined 177 GC cases, including 51 cases of CRA and 126 cases having conventional differentiated adenocarcinomas (CDAs). Results for immunohistochemistry (mucin phenotype; Muc5AC, Muc6, Muc2 and CD10, CDX-2, MLH-1, p53 and β-catenin), mutation analysis (TP53, KRAS and BRAF), microsatellite instability (BAT25, BAT26, D2S123, D5S346 and D17S250), DNA methylation status by a two-panel method (RUNX3, MINT31, LOX, NEUROG1, ELMO1 and THBD), MLH-1 promoter methylation, and allelic imbalance (AI; 1p, 3p, 4p, 5q, 8p, 9p, 13q, TP53, 18q and 22q) were examined. Results CRAs were more likely to occur in the middle third of the stomach, in younger patients and to be macroscopically depressed. Nuclear accumulation of β-catenin and loss of MLH-1 expression were less frequent among CRA cases compared to CDA cases. At a molecular level, CRA is often characterized by the deletion mutation c.529_546 (18-base pair deletion at codon 177–182 in exon 5) in the TP53 gene (10 cases). Although the low methylation epigenotype was significantly more frequent for CRAs compared to CDAs, multiple AIs were more often seen in CRAs relative to CDAs. Conclusions The results demonstrated that TP53 mutations, particularly c.529_546del, and multiple AIs are closely associated with CRA carcinogenesis. Our results suggest that CRA is an independent entity of GC in terms of clinicopathologic and molecular findings.

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Analysis of clinicopathological and molecular features of crawling-type gastric adenocarcinoma

10.21203/rs.3.rs-37904/v2 ◽

2020 ◽

Author(s):

Yasuko Fujita ◽

Noriyuki Uesugi ◽

Ryo Sugimoto ◽

Makoto Eizuka ◽

Yosuke Toya ◽

...

Keyword(s):

Allelic Imbalance ◽

Methylation Status ◽

Tp53 Gene ◽

Nuclear Accumulation ◽

Molecular Characteristics ◽

Mucin Phenotype ◽

Molecular Features ◽

Base Pair Deletion ◽

Clinicopathological Findings ◽

Independent Entity

Abstract Background: Crawling-type adenocarcinoma (CRA) is an important gastric cancer (GC) subtype that exhibits a specific histological pattern and has characteristic clinicopathological findings. Despite its characteristic histology, little is known about the molecular characteristics of CRA. Methods: We examined 254 GC cases, including 51 cases of CRA and 126 cases having conventional differentiated adenocarcinomas (CDAs). Results for immunohistochemistry (mucin phenotype; Muc5AC, Muc6, Muc2 and CD10, CDX-2, MLH-1 and β-catenin), mutation analysis ( TP53 , KRAS and BRAF ), microsatellite instability (BAT25, BAT26, D2S123, D5S346 and D17S250), DNA methylation status by a two-panel method ( RUNX3 , MINT31 , LOX, NEUROG1 , ELMO1 and THBD ), MLH-1 promoter methylation, and allelic imbalance (AI; 1p, 3p, 4p, 5q, 8p, 9p, 13q, TP53, 18q and 22q) were examined. Results: CRAs were more likely to occur in the middle third of the stomach, in younger patients and to be macroscopically depressed. Nuclear accumulation of β-catenin and loss of MLH-1 expression were less frequent among CRA cases compared to CDA cases. At a molecular level, CRA is often characterized by the deletion mutation c.529_546 (18-base pair deletion at codon 177-182 in exon 5), in the TP53 gene (10 cases). Although the low methylation epigenotype was significantly more frequent for CRAs compared to CDAs, multiple AIs were more often seen in CRAs relative to CDAs. Conclusions: The results demonstrated that TP53 mutations, particularly c.529_546del, and multiple AIs are closely associated with CRA carcinogenesis. Our results suggest that CRA is an independent entity of GC in terms of clinicopathologic and molecular findings.

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Transcriptional Characterization of Stage I Epithelial Ovarian Cancer: A Multicentric Study

Cells ◽

10.3390/cells8121554 ◽

2019 ◽

Vol 8 (12) ◽

pp. 1554

Author(s):

Enrica Calura ◽

Matteo Ciciani ◽

Andrea Sambugaro ◽

Lara Paracchini ◽

Giuseppe Benvenuto ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Stage I ◽

Molecular Heterogeneity ◽

Low Grade ◽

Multicentric Study ◽

Molecular Alterations ◽

Molecular Features ◽

Signaling Axis ◽

Tumor Biopsies

Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs. It is characterized by a complex histopathological and molecular heterogeneity, and it is composed of five main histological subtypes (mucinous, endometrioid, clear cell and high, and low grade serous), which have peculiar genetic, molecular, and clinical characteristics. As it occurs less frequently than advanced-stage EOC, its molecular features have not been thoroughly investigated. In this study, using in silico approaches and gene expression data, on a multicentric cohort composed of 208 snap-frozen tumor biopsies, we explored the subtype-specific molecular alterations that regulate tumor aggressiveness in stage I EOC. We found that single genes rather than pathways are responsible for histotype specificities and that a cAMP-PKA-CREB1 signaling axis seems to play a central role in histotype differentiation. Moreover, our results indicate that immune response seems to be, at least in part, involved in histotype differences, as a higher immune-reactive behavior of serous and mucinous samples was observed with respect to other histotypes.

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Pancreatic Solid Pseudopapillary Neoplasm: Key Pathologic and Genetic Features

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2019-0473-ra ◽

2020 ◽

Vol 144 (7) ◽

pp. 829-837 ◽

Cited By ~ 4

Author(s):

Stefano La Rosa ◽

Massimo Bongiovanni

Keyword(s):

Good Prognosis ◽

Low Grade ◽

Solid Pseudopapillary Neoplasm ◽

Prognostic Features ◽

Molecular Alterations ◽

Immunohistochemical Markers ◽

Molecular Features ◽

Pubmed Database ◽

Genetic Features ◽

Solid Pseudopapillary Neoplasms

Context.— Solid pseudopapillary neoplasm of the pancreas is a low-grade malignant tumor generally associated with a good prognosis. Solid pseudopapillary neoplasms show peculiar morphologic features, but sometimes the differential diagnosis with other pancreatic neoplasms (ie, pancreatic neuroendocrine tumors) can be a challenging task, especially in cytologic or biopsy specimens. In these cases immunohistochemistry is a useful tool, but the diagnostic utility of several proposed immunohistochemical markers is questionable. In recent years, despite several attempts to characterize the pathogenetic, molecular, and prognostic features of solid pseudopapillary neoplasms, they still remain unclear. Objective.— To give the reader a comprehensive update on this entity. Data Sources.— The PubMed database (US National Library of Medicine) was searched using the following string: pseudopapillary tumor [AND/OR] neoplasm [AND/OR] pancreas. All articles written in English were included. In addition, because a heterogeneous terminology has been used in the past to define solid pseudopapillary neoplasms, the reference lists of each paper selected in the PubMed database were also reviewed. Conclusions.— This review gives a comprehensive update on the pathologic, clinical, and molecular features of solid pseudopapillary neoplasms, particularly addressing issues and challenges related to diagnosis. In addition, we have tried to correlate the molecular alterations with the morphologic and clinical features.

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Are Borrmann’s Types of Advanced Gastric Cancer Distinct Clinicopathological and Molecular Entities? A Western Study

Cancers ◽

10.3390/cancers13123081 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3081

Author(s):

Cristina Díaz del Arco ◽

Luis Ortega Medina ◽

Lourdes Estrada Muñoz ◽

Elena Molina Roldán ◽

M. Ángeles Cerón Nieto ◽

...

Keyword(s):

Gastric Cancer ◽

Intestinal Type ◽

Low Grade ◽

High Grade ◽

Asian Patients ◽

Molecular Features ◽

Type Iv ◽

Signet Ring ◽

Systemic Symptoms ◽

Biological Entities

Most studies on the clinicopathological impact of Borrmann classification for gastric cancer (GC) have been performed in Asian patients with type IV tumors, and immunohistochemical features of Borrmann types have scarcely been analyzed. We assessed the clinicopathological, molecular features and prognostic value of Borrmann types in all patients with advanced GC resected in a Western institution (n = 260). We observed a significant relationship between Borrmann types and age, systemic symptoms, tumor size, Laurén subtype, presence of signet-ring cells, infiltrative growth, high grade, tumor necrosis, HERCEPTEST positivity, microsatellite instability (MSI) and molecular subtypes. Polypoid GC showed systemic symptoms, intestinal-type histology, low grade, expansive growth and HERCEPTEST positivity. Fungating GC occurred in symptomatic older patients. It presented intestinal-type histology, infiltrative growth and necrosis. Ulcerated GC showed smaller size, intestinal-type histology, high grade and infiltrative growth. Most polypoid and ulcerated tumors were stable-p53-not overexpressed or microsatellite unstable. Flat lesions were high-grade diffuse tumors with no MSI, and occurred in younger and less symptomatic patients. No association was found between Borrmann classification and prognosis. According to our results, Borrmann types may represent distinct clinicopathological and biological entities. Further research should be conducted to confirm the role of Borrmann classification in the stratification of patients with advanced GC.

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Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations

International Journal of Molecular Sciences ◽

10.3390/ijms22094388 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4388

Author(s):

Alessandro Vanoli ◽

Federica Grillo ◽

Daniela Furlan ◽

Giovanni Arpa ◽

Oneda Grami ◽

...

Keyword(s):

Crohn’S Disease ◽

Small Bowel ◽

Crohn's Disease ◽

Cowden Syndrome ◽

Intestinal Type ◽

Precursor Lesions ◽

Molecular Alterations ◽

Molecular Features ◽

Gastric Type ◽

Small Intestinal

The wider use of gastrointestinal endoscopic procedures has led to an increased detection of small intestinal preneoplastic and neoplastic epithelial lesions, most of which are identified in the duodenum and ampullary region. Like their malignant counterparts, small intestinal glandular precursor lesions, which include adenomas and hamartomas, may arise sporadically or be associated with hereditary tumor syndromes, such as familial adenomatous polyposis, MUTYH-associated polyposis, Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and Cowden syndrome. In addition, dysplastic, preinvasive lesions have been observed adjacent to small bowel adenocarcinomas complicating immune-related disorders, such as celiac or Crohn’s disease. Adenomatous lesions may exhibit an intestinal-type, gastric-type, or, very rarely, serrated differentiation, related to different molecular pathogenetic mechanisms. Finally, in the background of multiple endocrine neoplasia 1 syndrome, precursor neuroendocrine growths have been described. In this review we offer a comprehensive description on the histo-molecular features of the main histotypes of small bowel epithelial precursors lesions, including: (i) sporadic adenomas (intestinal-type and gastric-type; non-ampullary and ampullary); (ii) syndromic adenomas; (iii) small bowel dysplasia in celiac and Crohn’s disease; (iv) serrated lesions; (v) hamartomatous lesions; and (vi) neuroendocrine precursor lesions.

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