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Different subtypes of intraductal papillary mucinous neoplasm in the pancreas have distinct pathways to pancreatic cancer progression
Background Intraductal papillary mucinous neoplasm (IPMN) is recognized as a precursor lesion to pancreatic cancer, a unique pathological entity. IPMN has subtypes with different clinical characteristics. However, the molecular mechanisms of cancer progression from IPMN remain largely unknown. In th...
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| Published in: | Journal of gastroenterology 2012-02, Vol.47 (2), p.203-213 |
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| container_issue | 2 |
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| container_title | Journal of gastroenterology |
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| creator | Mohri, Dai Asaoka, Yoshinari Ijichi, Hideaki Miyabayashi, Koji Kudo, Yotaro Seto, Motoko Ohta, Miki Tada, Motohisa Tanaka, Yasuo Ikenoue, Tsuneo Tateishi, Keisuke Isayama, Hiroyuki Kanai, Fumihiko Fukushima, Noriyoshi Tada, Minoru Kawabe, Takao Omata, Masao Koike, Kazuhiko |
| description | Background
Intraductal papillary mucinous neoplasm (IPMN) is recognized as a precursor lesion to pancreatic cancer, a unique pathological entity. IPMN has subtypes with different clinical characteristics. However, the molecular mechanisms of cancer progression from IPMN remain largely unknown. In this study we examined the differences in genetic alteration(s) among the IPMN subtypes.
Methods
Surgically resected IPMNs (
n
= 25) were classified into four subtypes by hematoxylin and eosin (H&E) and mucin immunostaining. Mutations in
KRAS
,
BRAF
, and
PIK3CA
genes and expression of CDKN2A, TP53, SMAD4, phospho-ERK, and phospho-SMAD1/5/8 proteins were examined.
Results
There were 11 gastric, 11 intestinal, one pancreatobiliary, and two oncocytic types in this study. We then compared the two major subtypes, gastric-type and intestinal-type IPMN. Gastric-type IPMN showed a significantly higher incidence of
KRAS
mutations (9/11, 81.8%) compared with intestinal type (3/11, 27.3%;
p
|
| doi_str_mv | 10.1007/s00535-011-0482-y |
| format | article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_922759948</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A714586011</galeid><sourcerecordid>A714586011</sourcerecordid><originalsourceid>FETCH-LOGICAL-c556t-9d849575dfe75a839af0328afe1b4806b5fd7183eb25839c659bccd65f4c90993</originalsourceid><addsrcrecordid>eNp1kc9u1DAQxi0EokvhAbggCw6cUuzETuJjVf5KlbjA2XKc8a6rxA62U7QPwHszq7QgEMgHWzO_bzwzHyHPObvgjHVvMmOykRXjvGKir6vjA7LjAiNS1fVDsmNKiIrzTpyRJznfMMYbJvvH5KyumeCKqx358dY7BwlCoXkdynGBTKOjPpRkxtUWM9HFLH6aTDrSebU-xDXTAHGZTJ6Ro-UAiASbwGR6MLdAR5-LD7ZguBy-m2OmJd4jxVtq8QmJLinuE-TsY3hKHjkzZXh2d5-Tr-_ffbn6WF1__vDp6vK6slK2pVJjL5Ts5Oigk6ZvlHGsqXvjgA-iZ-0g3djxvoGhlpi1rVSDtWMrnbCKKdWck9dbXfz72wq56NlnCzgdTrRmjWvrpFKiR_LlX-RNXFPA5k4Qbo-1HUKvNmhvJtA-uIhbs6eS-rLjQvYtWoPUxT8oPCPM3sYAzmP8DwHfBDbFnBM4vSQ_owGaM30yXm_Ga4T1yXh9RM2Lu37XYYbxl-LeaQTqDciYCntIvwf6f9Wf4IK6Yw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>922041067</pqid></control><display><type>article</type><title>Different subtypes of intraductal papillary mucinous neoplasm in the pancreas have distinct pathways to pancreatic cancer progression</title><source>Springer Link</source><creator>Mohri, Dai ; Asaoka, Yoshinari ; Ijichi, Hideaki ; Miyabayashi, Koji ; Kudo, Yotaro ; Seto, Motoko ; Ohta, Miki ; Tada, Motohisa ; Tanaka, Yasuo ; Ikenoue, Tsuneo ; Tateishi, Keisuke ; Isayama, Hiroyuki ; Kanai, Fumihiko ; Fukushima, Noriyoshi ; Tada, Minoru ; Kawabe, Takao ; Omata, Masao ; Koike, Kazuhiko</creator><creatorcontrib>Mohri, Dai ; Asaoka, Yoshinari ; Ijichi, Hideaki ; Miyabayashi, Koji ; Kudo, Yotaro ; Seto, Motoko ; Ohta, Miki ; Tada, Motohisa ; Tanaka, Yasuo ; Ikenoue, Tsuneo ; Tateishi, Keisuke ; Isayama, Hiroyuki ; Kanai, Fumihiko ; Fukushima, Noriyoshi ; Tada, Minoru ; Kawabe, Takao ; Omata, Masao ; Koike, Kazuhiko</creatorcontrib><description>Background
Intraductal papillary mucinous neoplasm (IPMN) is recognized as a precursor lesion to pancreatic cancer, a unique pathological entity. IPMN has subtypes with different clinical characteristics. However, the molecular mechanisms of cancer progression from IPMN remain largely unknown. In this study we examined the differences in genetic alteration(s) among the IPMN subtypes.
Methods
Surgically resected IPMNs (
n
= 25) were classified into four subtypes by hematoxylin and eosin (H&E) and mucin immunostaining. Mutations in
KRAS
,
BRAF
, and
PIK3CA
genes and expression of CDKN2A, TP53, SMAD4, phospho-ERK, and phospho-SMAD1/5/8 proteins were examined.
Results
There were 11 gastric, 11 intestinal, one pancreatobiliary, and two oncocytic types in this study. We then compared the two major subtypes, gastric-type and intestinal-type IPMN. Gastric-type IPMN showed a significantly higher incidence of
KRAS
mutations (9/11, 81.8%) compared with intestinal type (3/11, 27.3%;
p
< 0.05), although the intestinal type showed a higher grade of dysplasia than gastric type (
p
< 0.01). All cases with
KRAS
mutations showed phospho-ERK immunostaining. In contrast, intestinal type (9/11, 81.8%) showed more frequent SMAD1/5/8 phosphorylation compared with gastric-type IPMN (3/11, 27.3%;
p
< 0.05%).
Conclusions
There may be distinct mechanisms of pancreatic cancer progression in the different subtypes of IPMN. In particular,
KRAS
mutation and bone morphogenetic protein-SMAD signaling status may be crucial diverging steps for the two representative pathways to pancreatic cancer in IPMN patients.</description><identifier>ISSN: 0944-1174</identifier><identifier>EISSN: 1435-5922</identifier><identifier>DOI: 10.1007/s00535-011-0482-y</identifier><identifier>PMID: 22041919</identifier><language>eng</language><publisher>Japan: Springer Japan</publisher><subject>Abdominal Surgery ; Adenocarcinoma, Mucinous - genetics ; Adult ; Aged ; Biliary Tract ; Bone Morphogenetic Proteins - physiology ; Cancer ; Carcinoma, Pancreatic Ductal - genetics ; Carcinoma, Pancreatic Ductal - pathology ; Class I Phosphatidylinositol 3-Kinases ; Colorectal Surgery ; Cyclin-Dependent Kinase Inhibitor p16 - metabolism ; Development and progression ; Disease Progression ; DNA Mutational Analysis ; Female ; Gastroenterology ; Gene Expression Regulation, Neoplastic - genetics ; Genetic research ; Hepatology ; Humans ; Immunohistochemistry ; Male ; Medical colleges ; Medicine ; Medicine & Public Health ; Middle Aged ; Oncology, Experimental ; Original Article—Liver ; Pancreas ; Pancreatic cancer ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - pathology ; Phosphatidylinositol 3-Kinases - genetics ; Protein Tyrosine Phosphatases - metabolism ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins B-raf - genetics ; Proto-Oncogene Proteins p21(ras) ; ras Proteins - genetics ; Signal Transduction - genetics ; Smad Proteins - physiology ; Surgical Oncology ; Tumor proteins ; Tumor Suppressor Protein p53 - metabolism</subject><ispartof>Journal of gastroenterology, 2012-02, Vol.47 (2), p.203-213</ispartof><rights>Springer 2011</rights><rights>COPYRIGHT 2012 Springer</rights><rights>Springer 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c556t-9d849575dfe75a839af0328afe1b4806b5fd7183eb25839c659bccd65f4c90993</citedby><cites>FETCH-LOGICAL-c556t-9d849575dfe75a839af0328afe1b4806b5fd7183eb25839c659bccd65f4c90993</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22041919$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mohri, Dai</creatorcontrib><creatorcontrib>Asaoka, Yoshinari</creatorcontrib><creatorcontrib>Ijichi, Hideaki</creatorcontrib><creatorcontrib>Miyabayashi, Koji</creatorcontrib><creatorcontrib>Kudo, Yotaro</creatorcontrib><creatorcontrib>Seto, Motoko</creatorcontrib><creatorcontrib>Ohta, Miki</creatorcontrib><creatorcontrib>Tada, Motohisa</creatorcontrib><creatorcontrib>Tanaka, Yasuo</creatorcontrib><creatorcontrib>Ikenoue, Tsuneo</creatorcontrib><creatorcontrib>Tateishi, Keisuke</creatorcontrib><creatorcontrib>Isayama, Hiroyuki</creatorcontrib><creatorcontrib>Kanai, Fumihiko</creatorcontrib><creatorcontrib>Fukushima, Noriyoshi</creatorcontrib><creatorcontrib>Tada, Minoru</creatorcontrib><creatorcontrib>Kawabe, Takao</creatorcontrib><creatorcontrib>Omata, Masao</creatorcontrib><creatorcontrib>Koike, Kazuhiko</creatorcontrib><title>Different subtypes of intraductal papillary mucinous neoplasm in the pancreas have distinct pathways to pancreatic cancer progression</title><title>Journal of gastroenterology</title><addtitle>J Gastroenterol</addtitle><addtitle>J Gastroenterol</addtitle><description>Background
Intraductal papillary mucinous neoplasm (IPMN) is recognized as a precursor lesion to pancreatic cancer, a unique pathological entity. IPMN has subtypes with different clinical characteristics. However, the molecular mechanisms of cancer progression from IPMN remain largely unknown. In this study we examined the differences in genetic alteration(s) among the IPMN subtypes.
Methods
Surgically resected IPMNs (
n
= 25) were classified into four subtypes by hematoxylin and eosin (H&E) and mucin immunostaining. Mutations in
KRAS
,
BRAF
, and
PIK3CA
genes and expression of CDKN2A, TP53, SMAD4, phospho-ERK, and phospho-SMAD1/5/8 proteins were examined.
Results
There were 11 gastric, 11 intestinal, one pancreatobiliary, and two oncocytic types in this study. We then compared the two major subtypes, gastric-type and intestinal-type IPMN. Gastric-type IPMN showed a significantly higher incidence of
KRAS
mutations (9/11, 81.8%) compared with intestinal type (3/11, 27.3%;
p
< 0.05), although the intestinal type showed a higher grade of dysplasia than gastric type (
p
< 0.01). All cases with
KRAS
mutations showed phospho-ERK immunostaining. In contrast, intestinal type (9/11, 81.8%) showed more frequent SMAD1/5/8 phosphorylation compared with gastric-type IPMN (3/11, 27.3%;
p
< 0.05%).
Conclusions
There may be distinct mechanisms of pancreatic cancer progression in the different subtypes of IPMN. In particular,
KRAS
mutation and bone morphogenetic protein-SMAD signaling status may be crucial diverging steps for the two representative pathways to pancreatic cancer in IPMN patients.</description><subject>Abdominal Surgery</subject><subject>Adenocarcinoma, Mucinous - genetics</subject><subject>Adult</subject><subject>Aged</subject><subject>Biliary Tract</subject><subject>Bone Morphogenetic Proteins - physiology</subject><subject>Cancer</subject><subject>Carcinoma, Pancreatic Ductal - genetics</subject><subject>Carcinoma, Pancreatic Ductal - pathology</subject><subject>Class I Phosphatidylinositol 3-Kinases</subject><subject>Colorectal Surgery</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>DNA Mutational Analysis</subject><subject>Female</subject><subject>Gastroenterology</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Genetic research</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Medical colleges</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Oncology, Experimental</subject><subject>Original Article—Liver</subject><subject>Pancreas</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Phosphatidylinositol 3-Kinases - genetics</subject><subject>Protein Tyrosine Phosphatases - metabolism</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>Proto-Oncogene Proteins p21(ras)</subject><subject>ras Proteins - genetics</subject><subject>Signal Transduction - genetics</subject><subject>Smad Proteins - physiology</subject><subject>Surgical Oncology</subject><subject>Tumor proteins</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><issn>0944-1174</issn><issn>1435-5922</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNp1kc9u1DAQxi0EokvhAbggCw6cUuzETuJjVf5KlbjA2XKc8a6rxA62U7QPwHszq7QgEMgHWzO_bzwzHyHPObvgjHVvMmOykRXjvGKir6vjA7LjAiNS1fVDsmNKiIrzTpyRJznfMMYbJvvH5KyumeCKqx358dY7BwlCoXkdynGBTKOjPpRkxtUWM9HFLH6aTDrSebU-xDXTAHGZTJ6Ro-UAiASbwGR6MLdAR5-LD7ZguBy-m2OmJd4jxVtq8QmJLinuE-TsY3hKHjkzZXh2d5-Tr-_ffbn6WF1__vDp6vK6slK2pVJjL5Ts5Oigk6ZvlHGsqXvjgA-iZ-0g3djxvoGhlpi1rVSDtWMrnbCKKdWck9dbXfz72wq56NlnCzgdTrRmjWvrpFKiR_LlX-RNXFPA5k4Qbo-1HUKvNmhvJtA-uIhbs6eS-rLjQvYtWoPUxT8oPCPM3sYAzmP8DwHfBDbFnBM4vSQ_owGaM30yXm_Ga4T1yXh9RM2Lu37XYYbxl-LeaQTqDciYCntIvwf6f9Wf4IK6Yw</recordid><startdate>20120201</startdate><enddate>20120201</enddate><creator>Mohri, Dai</creator><creator>Asaoka, Yoshinari</creator><creator>Ijichi, Hideaki</creator><creator>Miyabayashi, Koji</creator><creator>Kudo, Yotaro</creator><creator>Seto, Motoko</creator><creator>Ohta, Miki</creator><creator>Tada, Motohisa</creator><creator>Tanaka, Yasuo</creator><creator>Ikenoue, Tsuneo</creator><creator>Tateishi, Keisuke</creator><creator>Isayama, Hiroyuki</creator><creator>Kanai, Fumihiko</creator><creator>Fukushima, Noriyoshi</creator><creator>Tada, Minoru</creator><creator>Kawabe, Takao</creator><creator>Omata, Masao</creator><creator>Koike, Kazuhiko</creator><general>Springer Japan</general><general>Springer</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20120201</creationdate><title>Different subtypes of intraductal papillary mucinous neoplasm in the pancreas have distinct pathways to pancreatic cancer progression</title><author>Mohri, Dai ; Asaoka, Yoshinari ; Ijichi, Hideaki ; Miyabayashi, Koji ; Kudo, Yotaro ; Seto, Motoko ; Ohta, Miki ; Tada, Motohisa ; Tanaka, Yasuo ; Ikenoue, Tsuneo ; Tateishi, Keisuke ; Isayama, Hiroyuki ; Kanai, Fumihiko ; Fukushima, Noriyoshi ; Tada, Minoru ; Kawabe, Takao ; Omata, Masao ; Koike, Kazuhiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c556t-9d849575dfe75a839af0328afe1b4806b5fd7183eb25839c659bccd65f4c90993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Abdominal Surgery</topic><topic>Adenocarcinoma, Mucinous - genetics</topic><topic>Adult</topic><topic>Aged</topic><topic>Biliary Tract</topic><topic>Bone Morphogenetic Proteins - physiology</topic><topic>Cancer</topic><topic>Carcinoma, Pancreatic Ductal - genetics</topic><topic>Carcinoma, Pancreatic Ductal - pathology</topic><topic>Class I Phosphatidylinositol 3-Kinases</topic><topic>Colorectal Surgery</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</topic><topic>Development and progression</topic><topic>Disease Progression</topic><topic>DNA Mutational Analysis</topic><topic>Female</topic><topic>Gastroenterology</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Genetic research</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Medical colleges</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Oncology, Experimental</topic><topic>Original Article—Liver</topic><topic>Pancreas</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Phosphatidylinositol 3-Kinases - genetics</topic><topic>Protein Tyrosine Phosphatases - metabolism</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><topic>Proto-Oncogene Proteins p21(ras)</topic><topic>ras Proteins - genetics</topic><topic>Signal Transduction - genetics</topic><topic>Smad Proteins - physiology</topic><topic>Surgical Oncology</topic><topic>Tumor proteins</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mohri, Dai</creatorcontrib><creatorcontrib>Asaoka, Yoshinari</creatorcontrib><creatorcontrib>Ijichi, Hideaki</creatorcontrib><creatorcontrib>Miyabayashi, Koji</creatorcontrib><creatorcontrib>Kudo, Yotaro</creatorcontrib><creatorcontrib>Seto, Motoko</creatorcontrib><creatorcontrib>Ohta, Miki</creatorcontrib><creatorcontrib>Tada, Motohisa</creatorcontrib><creatorcontrib>Tanaka, Yasuo</creatorcontrib><creatorcontrib>Ikenoue, Tsuneo</creatorcontrib><creatorcontrib>Tateishi, Keisuke</creatorcontrib><creatorcontrib>Isayama, Hiroyuki</creatorcontrib><creatorcontrib>Kanai, Fumihiko</creatorcontrib><creatorcontrib>Fukushima, Noriyoshi</creatorcontrib><creatorcontrib>Tada, Minoru</creatorcontrib><creatorcontrib>Kawabe, Takao</creatorcontrib><creatorcontrib>Omata, Masao</creatorcontrib><creatorcontrib>Koike, Kazuhiko</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database (ProQuest)</collection><collection>Immunology Abstracts</collection><collection>PHMC-Proquest健康医学期刊库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of gastroenterology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mohri, Dai</au><au>Asaoka, Yoshinari</au><au>Ijichi, Hideaki</au><au>Miyabayashi, Koji</au><au>Kudo, Yotaro</au><au>Seto, Motoko</au><au>Ohta, Miki</au><au>Tada, Motohisa</au><au>Tanaka, Yasuo</au><au>Ikenoue, Tsuneo</au><au>Tateishi, Keisuke</au><au>Isayama, Hiroyuki</au><au>Kanai, Fumihiko</au><au>Fukushima, Noriyoshi</au><au>Tada, Minoru</au><au>Kawabe, Takao</au><au>Omata, Masao</au><au>Koike, Kazuhiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Different subtypes of intraductal papillary mucinous neoplasm in the pancreas have distinct pathways to pancreatic cancer progression</atitle><jtitle>Journal of gastroenterology</jtitle><stitle>J Gastroenterol</stitle><addtitle>J Gastroenterol</addtitle><date>2012-02-01</date><risdate>2012</risdate><volume>47</volume><issue>2</issue><spage>203</spage><epage>213</epage><pages>203-213</pages><issn>0944-1174</issn><eissn>1435-5922</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Background
Intraductal papillary mucinous neoplasm (IPMN) is recognized as a precursor lesion to pancreatic cancer, a unique pathological entity. IPMN has subtypes with different clinical characteristics. However, the molecular mechanisms of cancer progression from IPMN remain largely unknown. In this study we examined the differences in genetic alteration(s) among the IPMN subtypes.
Methods
Surgically resected IPMNs (
n
= 25) were classified into four subtypes by hematoxylin and eosin (H&E) and mucin immunostaining. Mutations in
KRAS
,
BRAF
, and
PIK3CA
genes and expression of CDKN2A, TP53, SMAD4, phospho-ERK, and phospho-SMAD1/5/8 proteins were examined.
Results
There were 11 gastric, 11 intestinal, one pancreatobiliary, and two oncocytic types in this study. We then compared the two major subtypes, gastric-type and intestinal-type IPMN. Gastric-type IPMN showed a significantly higher incidence of
KRAS
mutations (9/11, 81.8%) compared with intestinal type (3/11, 27.3%;
p
< 0.05), although the intestinal type showed a higher grade of dysplasia than gastric type (
p
< 0.01). All cases with
KRAS
mutations showed phospho-ERK immunostaining. In contrast, intestinal type (9/11, 81.8%) showed more frequent SMAD1/5/8 phosphorylation compared with gastric-type IPMN (3/11, 27.3%;
p
< 0.05%).
Conclusions
There may be distinct mechanisms of pancreatic cancer progression in the different subtypes of IPMN. In particular,
KRAS
mutation and bone morphogenetic protein-SMAD signaling status may be crucial diverging steps for the two representative pathways to pancreatic cancer in IPMN patients.</abstract><cop>Japan</cop><pub>Springer Japan</pub><pmid>22041919</pmid><doi>10.1007/s00535-011-0482-y</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0944-1174 |
| ispartof | Journal of gastroenterology, 2012-02, Vol.47 (2), p.203-213 |
| issn | 0944-1174 1435-5922 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_922759948 |
| source | Springer Link |
| subjects | Abdominal Surgery Adenocarcinoma, Mucinous - genetics Adult Aged Biliary Tract Bone Morphogenetic Proteins - physiology Cancer Carcinoma, Pancreatic Ductal - genetics Carcinoma, Pancreatic Ductal - pathology Class I Phosphatidylinositol 3-Kinases Colorectal Surgery Cyclin-Dependent Kinase Inhibitor p16 - metabolism Development and progression Disease Progression DNA Mutational Analysis Female Gastroenterology Gene Expression Regulation, Neoplastic - genetics Genetic research Hepatology Humans Immunohistochemistry Male Medical colleges Medicine Medicine & Public Health Middle Aged Oncology, Experimental Original Article—Liver Pancreas Pancreatic cancer Pancreatic Neoplasms - genetics Pancreatic Neoplasms - pathology Phosphatidylinositol 3-Kinases - genetics Protein Tyrosine Phosphatases - metabolism Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins B-raf - genetics Proto-Oncogene Proteins p21(ras) ras Proteins - genetics Signal Transduction - genetics Smad Proteins - physiology Surgical Oncology Tumor proteins Tumor Suppressor Protein p53 - metabolism |
| title | Different subtypes of intraductal papillary mucinous neoplasm in the pancreas have distinct pathways to pancreatic cancer progression |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-22T13%3A29%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Different%20subtypes%20of%20intraductal%20papillary%20mucinous%20neoplasm%20in%20the%20pancreas%20have%20distinct%20pathways%20to%20pancreatic%20cancer%20progression&rft.jtitle=Journal%20of%20gastroenterology&rft.au=Mohri,%20Dai&rft.date=2012-02-01&rft.volume=47&rft.issue=2&rft.spage=203&rft.epage=213&rft.pages=203-213&rft.issn=0944-1174&rft.eissn=1435-5922&rft_id=info:doi/10.1007/s00535-011-0482-y&rft_dat=%3Cgale_proqu%3EA714586011%3C/gale_proqu%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c556t-9d849575dfe75a839af0328afe1b4806b5fd7183eb25839c659bccd65f4c90993%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=922041067&rft_id=info:pmid/22041919&rft_galeid=A714586011&rfr_iscdi=true |