Multiple KRAS mutations in the non-mucinous epithelial lining in the majority of mucinous cystic neoplasms of the pancreas

Soyeon An, Mi Ju Kim, Sung Joo Kim, You Na Sung, Yeon Wook Kim, Ki Byung Song, Dae Wook Hwang, Song Cheol Kim, Ralph H Hruban, Seung Mo Hong

Research output: Contribution to journalArticle

Abstract

Aims: Mucinous cystic neoplasms (MCNs) of the pancreas are cystic neoplasms lined by mucinous lining epithelium (MLE) with associated ovarian-type stroma. Although a non-MLE (NMLE) can be observed in some MCNs, whether cystic neoplasms with ovarian-type stroma and NMLE should be classified as MCNs or separately designated is debated. Methods and results: To test this, NMLEs were defined as flat or cuboidal epithelial cells without intracytoplasmic mucin. A total of 112 MCNs were reviewed, and the epithelium was classified as NMLE or MLE. A total of 110 females and two males with a mean age of 46.5 ± 12.3 years were included in this study. At least focal NMLE was noted in 76.8% (86/112) of MCNs. The mean percentage of the neoplastic epithelium that was NMLE in these 86 cases was 46%. NMLE was predominant (>50%) in 38.4% (43/112) of cases. MCNs with NMLE were smaller (42 ± 21 mm) than those with MLE (60 ± 36 mm, P < 0.001), and all NMLEs had low-grade dysplasia. Twelve MCNs with NMLE or MLE were selected for KRAS mutation analysis with droplet digital polymerase chain reaction after laser capture microdissection. All 12 MCNs showed multiple types of KRAS mutation, which were detected in 92% (11/12) of NMLE foci and 89% (8/9) of MLE foci. Predominant NMLE was common in small MCNs with low-grade dysplasia. Conclusions: Clonal KRAS mutations were observed in both NMLE and MLE, supporting the hypothesis that MCNs with NMLE should be classified as MCNs.

Original languageEnglish (US)
Pages (from-to)559-567
Number of pages9
JournalHistopathology
Volume75
Issue number4
DOIs
StatePublished - Oct 1 2019

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Pancreatic Neoplasms
Epithelium
Mutation
Neoplasms
Laser Capture Microdissection
Mucins
Ovarian Neoplasms
Epithelial Cells
Polymerase Chain Reaction

Keywords

  • epithelium
  • KRAS
  • mucinous cystic neoplasm
  • non-mucinous
  • pancreas

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

An, S., Kim, M. J., Kim, S. J., Sung, Y. N., Kim, Y. W., Song, K. B., ... Hong, S. M. (2019). Multiple KRAS mutations in the non-mucinous epithelial lining in the majority of mucinous cystic neoplasms of the pancreas. Histopathology, 75(4), 559-567. https://doi.org/10.1111/his.13897

Multiple KRAS mutations in the non-mucinous epithelial lining in the majority of mucinous cystic neoplasms of the pancreas. / An, Soyeon; Kim, Mi Ju; Kim, Sung Joo; Sung, You Na; Kim, Yeon Wook; Song, Ki Byung; Hwang, Dae Wook; Kim, Song Cheol; Hruban, Ralph H; Hong, Seung Mo.

In: Histopathology, Vol. 75, No. 4, 01.10.2019, p. 559-567.

Research output: Contribution to journalArticle

An, S, Kim, MJ, Kim, SJ, Sung, YN, Kim, YW, Song, KB, Hwang, DW, Kim, SC, Hruban, RH & Hong, SM 2019, 'Multiple KRAS mutations in the non-mucinous epithelial lining in the majority of mucinous cystic neoplasms of the pancreas', Histopathology, vol. 75, no. 4, pp. 559-567. https://doi.org/10.1111/his.13897
An, Soyeon ; Kim, Mi Ju ; Kim, Sung Joo ; Sung, You Na ; Kim, Yeon Wook ; Song, Ki Byung ; Hwang, Dae Wook ; Kim, Song Cheol ; Hruban, Ralph H ; Hong, Seung Mo. / Multiple KRAS mutations in the non-mucinous epithelial lining in the majority of mucinous cystic neoplasms of the pancreas. In: Histopathology. 2019 ; Vol. 75, No. 4. pp. 559-567.
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abstract = "Aims: Mucinous cystic neoplasms (MCNs) of the pancreas are cystic neoplasms lined by mucinous lining epithelium (MLE) with associated ovarian-type stroma. Although a non-MLE (NMLE) can be observed in some MCNs, whether cystic neoplasms with ovarian-type stroma and NMLE should be classified as MCNs or separately designated is debated. Methods and results: To test this, NMLEs were defined as flat or cuboidal epithelial cells without intracytoplasmic mucin. A total of 112 MCNs were reviewed, and the epithelium was classified as NMLE or MLE. A total of 110 females and two males with a mean age of 46.5 ± 12.3 years were included in this study. At least focal NMLE was noted in 76.8{\%} (86/112) of MCNs. The mean percentage of the neoplastic epithelium that was NMLE in these 86 cases was 46{\%}. NMLE was predominant (>50{\%}) in 38.4{\%} (43/112) of cases. MCNs with NMLE were smaller (42 ± 21 mm) than those with MLE (60 ± 36 mm, P < 0.001), and all NMLEs had low-grade dysplasia. Twelve MCNs with NMLE or MLE were selected for KRAS mutation analysis with droplet digital polymerase chain reaction after laser capture microdissection. All 12 MCNs showed multiple types of KRAS mutation, which were detected in 92{\%} (11/12) of NMLE foci and 89{\%} (8/9) of MLE foci. Predominant NMLE was common in small MCNs with low-grade dysplasia. Conclusions: Clonal KRAS mutations were observed in both NMLE and MLE, supporting the hypothesis that MCNs with NMLE should be classified as MCNs.",
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T1 - Multiple KRAS mutations in the non-mucinous epithelial lining in the majority of mucinous cystic neoplasms of the pancreas

AU - An, Soyeon

AU - Kim, Mi Ju

AU - Kim, Sung Joo

AU - Sung, You Na

AU - Kim, Yeon Wook

AU - Song, Ki Byung

AU - Hwang, Dae Wook

AU - Kim, Song Cheol

AU - Hruban, Ralph H

AU - Hong, Seung Mo

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Aims: Mucinous cystic neoplasms (MCNs) of the pancreas are cystic neoplasms lined by mucinous lining epithelium (MLE) with associated ovarian-type stroma. Although a non-MLE (NMLE) can be observed in some MCNs, whether cystic neoplasms with ovarian-type stroma and NMLE should be classified as MCNs or separately designated is debated. Methods and results: To test this, NMLEs were defined as flat or cuboidal epithelial cells without intracytoplasmic mucin. A total of 112 MCNs were reviewed, and the epithelium was classified as NMLE or MLE. A total of 110 females and two males with a mean age of 46.5 ± 12.3 years were included in this study. At least focal NMLE was noted in 76.8% (86/112) of MCNs. The mean percentage of the neoplastic epithelium that was NMLE in these 86 cases was 46%. NMLE was predominant (>50%) in 38.4% (43/112) of cases. MCNs with NMLE were smaller (42 ± 21 mm) than those with MLE (60 ± 36 mm, P < 0.001), and all NMLEs had low-grade dysplasia. Twelve MCNs with NMLE or MLE were selected for KRAS mutation analysis with droplet digital polymerase chain reaction after laser capture microdissection. All 12 MCNs showed multiple types of KRAS mutation, which were detected in 92% (11/12) of NMLE foci and 89% (8/9) of MLE foci. Predominant NMLE was common in small MCNs with low-grade dysplasia. Conclusions: Clonal KRAS mutations were observed in both NMLE and MLE, supporting the hypothesis that MCNs with NMLE should be classified as MCNs.

AB - Aims: Mucinous cystic neoplasms (MCNs) of the pancreas are cystic neoplasms lined by mucinous lining epithelium (MLE) with associated ovarian-type stroma. Although a non-MLE (NMLE) can be observed in some MCNs, whether cystic neoplasms with ovarian-type stroma and NMLE should be classified as MCNs or separately designated is debated. Methods and results: To test this, NMLEs were defined as flat or cuboidal epithelial cells without intracytoplasmic mucin. A total of 112 MCNs were reviewed, and the epithelium was classified as NMLE or MLE. A total of 110 females and two males with a mean age of 46.5 ± 12.3 years were included in this study. At least focal NMLE was noted in 76.8% (86/112) of MCNs. The mean percentage of the neoplastic epithelium that was NMLE in these 86 cases was 46%. NMLE was predominant (>50%) in 38.4% (43/112) of cases. MCNs with NMLE were smaller (42 ± 21 mm) than those with MLE (60 ± 36 mm, P < 0.001), and all NMLEs had low-grade dysplasia. Twelve MCNs with NMLE or MLE were selected for KRAS mutation analysis with droplet digital polymerase chain reaction after laser capture microdissection. All 12 MCNs showed multiple types of KRAS mutation, which were detected in 92% (11/12) of NMLE foci and 89% (8/9) of MLE foci. Predominant NMLE was common in small MCNs with low-grade dysplasia. Conclusions: Clonal KRAS mutations were observed in both NMLE and MLE, supporting the hypothesis that MCNs with NMLE should be classified as MCNs.

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