TY - JOUR
T1 - Intraductal papillary neoplasms of the bile duct consist of two distinct types specifically associated with clinicopathological features and molecular phenotypes
AU - Aoki, Yasutaka
AU - Mizuma, Masamichi
AU - Hata, Tatsuo
AU - Aoki, Takeshi
AU - Omori, Yuko
AU - Ono, Yusuke
AU - Mizukami, Yusuke
AU - Unno, Michiaki
AU - Furukawa, Toru
N1 - Funding Information:
We are grateful to Ms. Fumiko Date, Tohoku University Graduate School of Medicine, for her technical assistance; Ms. Yuko Hayakawa, Sapporo Higashi Tokushukai Hospital, for her technical support in the genetic analyses; and Mr. Osamu Takahashi (Thermo Fisher Scientific) for technical support regarding the sequencing analyses. This work was supported by JSPS KAKENHI Grant Number JP16H05410 to MU.
Funding Information:
We are grateful to Ms. Fumiko Date, Tohoku University Graduate School of Medicine, for her technical assistance; Ms. Yuko Hayakawa, Sapporo Higashi Tokushukai Hospital, for her technical support in the genetic analyses; and Mr. Osamu Takahashi (Thermo Fisher Scientific) for technical support regarding the sequencing analyses. This work was supported by JSPS KAKENHI Grant Number JP16H05410 to MU.
Publisher Copyright:
© 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Intraductal papillary neoplasm of the bile duct (IPNB) is a grossly visible papillary biliary neoplasm with morphological variations and occasional invasion. Recently a new classification of IPNB into type 1 and type 2 was proposed in which the type 1 IPNBs consist of fine papillary neoplastic glands and the type 2 IPNBs consist of complex branching glands, seldom with foci of solid-tubular components. However, clinicopathological and molecular characteristics of these types of IPNBs are yet to be identified. We aimed to uncover clinicopathological and molecular characteristics of the types of IPNBs. Thirty-six IPNBs were studied retrospectively. Clinicopathological features as well as molecular alterations of 31 genes were evaluated by means of targeted next-generation sequencing and immunohistochemical examination of expression of mucin and cancer-associated molecules. The 36 IPNBs were classified into 22 of type 1 and 14 of type 2. The type 1 IPNBs were associated with a non-invasive phenotype, intestinal and oncocytic subtypes, development in the intrahepatic bile duct, overt mucin production, and a relatively good prognosis. The type 2 IPNBs were associated with an invasive phenotype, the pancreatobiliary subtype, development within the extrahepatic bile duct, and worse prognosis compared with the type 1 IPNBs. In the molecular analysis, recurrent mutations were found in TP53 (34.3%), KRAS (31.4%), STK11 (25.7%), CTNNB1 (17.1%), APC (14.3%), SMAD4 (14.3%), GNAS (11.4%), PBRM1 (11.4%), ELF3 (8.6%), KMT2C (8.6%), NF1 (8.6%), PIK3CA (8.6%), ARID1A (5.7%), ARID2 (5.7%), BAP1 (5.7%), BRAF (5.7%), EPHA6 (5.7%), ERBB2 (5.7%), ERBB3 (5.7%), KMT2D (5.7%), and RNF43 (5.7%). Mutations in KRAS and GNAS were enriched in the type 1 IPNBs, whereas mutations in TP53, SMAD4, and KMT2C were enriched in the type 2 IPNBs. These results indicate that IPNBs consist of two distinct types of neoplasms specifically associated with clinicopathological features and molecular phenotypes.
AB - Intraductal papillary neoplasm of the bile duct (IPNB) is a grossly visible papillary biliary neoplasm with morphological variations and occasional invasion. Recently a new classification of IPNB into type 1 and type 2 was proposed in which the type 1 IPNBs consist of fine papillary neoplastic glands and the type 2 IPNBs consist of complex branching glands, seldom with foci of solid-tubular components. However, clinicopathological and molecular characteristics of these types of IPNBs are yet to be identified. We aimed to uncover clinicopathological and molecular characteristics of the types of IPNBs. Thirty-six IPNBs were studied retrospectively. Clinicopathological features as well as molecular alterations of 31 genes were evaluated by means of targeted next-generation sequencing and immunohistochemical examination of expression of mucin and cancer-associated molecules. The 36 IPNBs were classified into 22 of type 1 and 14 of type 2. The type 1 IPNBs were associated with a non-invasive phenotype, intestinal and oncocytic subtypes, development in the intrahepatic bile duct, overt mucin production, and a relatively good prognosis. The type 2 IPNBs were associated with an invasive phenotype, the pancreatobiliary subtype, development within the extrahepatic bile duct, and worse prognosis compared with the type 1 IPNBs. In the molecular analysis, recurrent mutations were found in TP53 (34.3%), KRAS (31.4%), STK11 (25.7%), CTNNB1 (17.1%), APC (14.3%), SMAD4 (14.3%), GNAS (11.4%), PBRM1 (11.4%), ELF3 (8.6%), KMT2C (8.6%), NF1 (8.6%), PIK3CA (8.6%), ARID1A (5.7%), ARID2 (5.7%), BAP1 (5.7%), BRAF (5.7%), EPHA6 (5.7%), ERBB2 (5.7%), ERBB3 (5.7%), KMT2D (5.7%), and RNF43 (5.7%). Mutations in KRAS and GNAS were enriched in the type 1 IPNBs, whereas mutations in TP53, SMAD4, and KMT2C were enriched in the type 2 IPNBs. These results indicate that IPNBs consist of two distinct types of neoplasms specifically associated with clinicopathological features and molecular phenotypes.
KW - biliary cancer
KW - cholangiocarcinoma
KW - genetics
KW - molecular subtyping
KW - prognosis
KW - targeted sequencing
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U2 - 10.1002/path.5398
DO - 10.1002/path.5398
M3 - Article
C2 - 32100878
AN - SCOPUS:85081202910
SN - 0022-3417
VL - 251
SP - 38
EP - 48
JO - Journal of Pathology
JF - Journal of Pathology
IS - 1
ER -
