Molecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant Progression
The malignant progression of pancreatic cystic lesions (PCLs) remains understudied with a knowledge gap, yet its exploration is pivotal for effectively stratifying patient risk and detecting cancer at its earliest stages. Within this review, we delve into the latest discoveries on the molecular leve...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/6/1183 |
| _version_ | 1797241729812791296 |
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| author | Yan Hu Dan Jones Ashwini K. Esnakula Somashekar G. Krishna Wei Chen |
| author_facet | Yan Hu Dan Jones Ashwini K. Esnakula Somashekar G. Krishna Wei Chen |
| author_sort | Yan Hu |
| collection | DOAJ |
| description | The malignant progression of pancreatic cystic lesions (PCLs) remains understudied with a knowledge gap, yet its exploration is pivotal for effectively stratifying patient risk and detecting cancer at its earliest stages. Within this review, we delve into the latest discoveries on the molecular level, revealing insights into the IPMN molecular landscape and revised progression model, associated histologic subtypes, and the role of inflammation in the pathogenesis and malignant progression of IPMN. Low-grade PCLs, particularly IPMNs, can develop into high-grade lesions or invasive carcinoma, underscoring the need for long-term surveillance of these lesions if they are not resected. Although <i>KRAS</i> and <i>GNAS</i> remain the primary oncogenic drivers of neoplastic development in IPMNs, additional genes that are important in tumorigenesis have been recently identified by whole exome sequencing. A more complete understanding of the genes involved in the molecular progression of IPMN is critical for effective monitoring to minimize the risk of malignant progression. Complicating these strategies, IPMNs are also frequently multifocal and multiclonal, as demonstrated by comparative molecular analysis. Algorithms for preoperative cyst sampling and improved radiomic techniques are emerging to model this spatial and temporal genetic heterogeneity better. Here, we review the molecular pathology of PCLs, focusing on changes associated with malignant progression. Developing models of molecular risk stratification in PCLs which can complement radiologic and clinical features, facilitate the early detection of pancreatic cancer, and enable the development of more personalized surveillance and management strategies are summarized. |
| first_indexed | 2024-04-24T18:27:58Z |
| format | Article |
| id | doaj.art-7177b8cefe98400fa4bacc292e5e4797 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-04-24T18:27:58Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7177b8cefe98400fa4bacc292e5e47972024-03-27T13:30:03ZengMDPI AGCancers2072-66942024-03-01166118310.3390/cancers16061183Molecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant ProgressionYan Hu0Dan Jones1Ashwini K. Esnakula2Somashekar G. Krishna3Wei Chen4James Molecular Laboratory, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USAJames Molecular Laboratory, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USADepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USADivision of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USADepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USAThe malignant progression of pancreatic cystic lesions (PCLs) remains understudied with a knowledge gap, yet its exploration is pivotal for effectively stratifying patient risk and detecting cancer at its earliest stages. Within this review, we delve into the latest discoveries on the molecular level, revealing insights into the IPMN molecular landscape and revised progression model, associated histologic subtypes, and the role of inflammation in the pathogenesis and malignant progression of IPMN. Low-grade PCLs, particularly IPMNs, can develop into high-grade lesions or invasive carcinoma, underscoring the need for long-term surveillance of these lesions if they are not resected. Although <i>KRAS</i> and <i>GNAS</i> remain the primary oncogenic drivers of neoplastic development in IPMNs, additional genes that are important in tumorigenesis have been recently identified by whole exome sequencing. A more complete understanding of the genes involved in the molecular progression of IPMN is critical for effective monitoring to minimize the risk of malignant progression. Complicating these strategies, IPMNs are also frequently multifocal and multiclonal, as demonstrated by comparative molecular analysis. Algorithms for preoperative cyst sampling and improved radiomic techniques are emerging to model this spatial and temporal genetic heterogeneity better. Here, we review the molecular pathology of PCLs, focusing on changes associated with malignant progression. Developing models of molecular risk stratification in PCLs which can complement radiologic and clinical features, facilitate the early detection of pancreatic cancer, and enable the development of more personalized surveillance and management strategies are summarized.https://www.mdpi.com/2072-6694/16/6/1183pancreatic cancermolecular mechanismsIPMNhistologic subtypesrisk stratificationmalignant progression |
| spellingShingle | Yan Hu Dan Jones Ashwini K. Esnakula Somashekar G. Krishna Wei Chen Molecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant Progression Cancers pancreatic cancer molecular mechanisms IPMN histologic subtypes risk stratification malignant progression |
| title | Molecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant Progression |
| title_full | Molecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant Progression |
| title_fullStr | Molecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant Progression |
| title_full_unstemmed | Molecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant Progression |
| title_short | Molecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant Progression |
| title_sort | molecular pathology of pancreatic cystic lesions with a focus on malignant progression |
| topic | pancreatic cancer molecular mechanisms IPMN histologic subtypes risk stratification malignant progression |
| url | https://www.mdpi.com/2072-6694/16/6/1183 |
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