Insulinoma-associated Protein 1 (INSM1) Expression in Small Cell Neuroendocrine Carcinoma of the Urinary Tract

Isaac E. Kim, Ali Amin, Li Juan Wang, Liang Cheng, Carmen M. Perrino

Research output: Contribution to journalArticle

Abstract

Clinical guidelines state that neoadjuvant chemotherapy should be administered before surgery in muscle invasive urinary bladder small cell neuroendocrine carcinoma. Recently described marker insulinoma-associated protein 1 (INSM1) has been reported to be sensitive and specific for neuroendocrine differentiation, however, its efficacy in urinary tract small cell carcinoma is not well established. This study examines immunohistochemical expression of INSM1 on whole tissue sections of urinary tract small cell neuroendocrine carcinoma and compares INSM1 expression with established neuroendocrine markers. Immunohistochemical stains for CD56, INSM1, synaptophysin, and chromogranin were performed on 32 cases of small cell neuroendocrine carcinoma of the bladder. Staining was scored for intensity (0: No staining; 1: Weak; 2: Moderate; 3: Strong) and proportion of cells stained (0: 0%; 1: >0% to ≤25%; 2: >25% to ≤50%; 3: >50% to ≤75%; 4: >75% to 100%). INSM1 was positive (intensity 1 to 3 or proportion 1 to 4) in 87% (28/32) of cases (20 with intensity 2 to 3, 17 with proportion 3 to 4). CD56, synaptophysin, and chromogranin were positive in 75% (24/32), 60% (19/32), and 44% (14/32) of cases, respectively. INSM1 was negative (n=4) or only showed weak intensity staining (n=7) in 34% (11/32) of cases. INSM1 is a sensitive marker of small cell neuroendocrine differentiation of the urinary tract. However, this study suggests that optimal utilization of INSM1 would be inclusion in a limited panel of stains rather than as a stand-alone screening marker given that it is negative or only shows weak intensity staining in a significant proportion of cases.

Original languageEnglish (US)
JournalApplied Immunohistochemistry and Molecular Morphology
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Neuroendocrine Carcinoma
Insulinoma
Small Cell Carcinoma
Urinary Tract
Proteins
Staining and Labeling
Chromogranins
Synaptophysin
Urinary Bladder
Coloring Agents
Cell Differentiation
Guidelines
Drug Therapy
Muscles

Keywords

  • bladder
  • INSM1
  • neuroendocrine
  • small cell
  • urinary bladder

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Medical Laboratory Technology

Cite this

Insulinoma-associated Protein 1 (INSM1) Expression in Small Cell Neuroendocrine Carcinoma of the Urinary Tract. / Kim, Isaac E.; Amin, Ali; Wang, Li Juan; Cheng, Liang; Perrino, Carmen M.

In: Applied Immunohistochemistry and Molecular Morphology, 01.01.2019.

Research output: Contribution to journalArticle

@article{09c7012e49384c0fb0ac453d92abac31,
title = "Insulinoma-associated Protein 1 (INSM1) Expression in Small Cell Neuroendocrine Carcinoma of the Urinary Tract",
abstract = "Clinical guidelines state that neoadjuvant chemotherapy should be administered before surgery in muscle invasive urinary bladder small cell neuroendocrine carcinoma. Recently described marker insulinoma-associated protein 1 (INSM1) has been reported to be sensitive and specific for neuroendocrine differentiation, however, its efficacy in urinary tract small cell carcinoma is not well established. This study examines immunohistochemical expression of INSM1 on whole tissue sections of urinary tract small cell neuroendocrine carcinoma and compares INSM1 expression with established neuroendocrine markers. Immunohistochemical stains for CD56, INSM1, synaptophysin, and chromogranin were performed on 32 cases of small cell neuroendocrine carcinoma of the bladder. Staining was scored for intensity (0: No staining; 1: Weak; 2: Moderate; 3: Strong) and proportion of cells stained (0: 0{\%}; 1: >0{\%} to ≤25{\%}; 2: >25{\%} to ≤50{\%}; 3: >50{\%} to ≤75{\%}; 4: >75{\%} to 100{\%}). INSM1 was positive (intensity 1 to 3 or proportion 1 to 4) in 87{\%} (28/32) of cases (20 with intensity 2 to 3, 17 with proportion 3 to 4). CD56, synaptophysin, and chromogranin were positive in 75{\%} (24/32), 60{\%} (19/32), and 44{\%} (14/32) of cases, respectively. INSM1 was negative (n=4) or only showed weak intensity staining (n=7) in 34{\%} (11/32) of cases. INSM1 is a sensitive marker of small cell neuroendocrine differentiation of the urinary tract. However, this study suggests that optimal utilization of INSM1 would be inclusion in a limited panel of stains rather than as a stand-alone screening marker given that it is negative or only shows weak intensity staining in a significant proportion of cases.",
keywords = "bladder, INSM1, neuroendocrine, small cell, urinary bladder",
author = "Kim, {Isaac E.} and Ali Amin and Wang, {Li Juan} and Liang Cheng and Perrino, {Carmen M.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1097/PAI.0000000000000824",
language = "English (US)",
journal = "Applied Immunohistochemistry and Molecular Morphology",
issn = "1541-2016",
publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - Insulinoma-associated Protein 1 (INSM1) Expression in Small Cell Neuroendocrine Carcinoma of the Urinary Tract

AU - Kim, Isaac E.

AU - Amin, Ali

AU - Wang, Li Juan

AU - Cheng, Liang

AU - Perrino, Carmen M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Clinical guidelines state that neoadjuvant chemotherapy should be administered before surgery in muscle invasive urinary bladder small cell neuroendocrine carcinoma. Recently described marker insulinoma-associated protein 1 (INSM1) has been reported to be sensitive and specific for neuroendocrine differentiation, however, its efficacy in urinary tract small cell carcinoma is not well established. This study examines immunohistochemical expression of INSM1 on whole tissue sections of urinary tract small cell neuroendocrine carcinoma and compares INSM1 expression with established neuroendocrine markers. Immunohistochemical stains for CD56, INSM1, synaptophysin, and chromogranin were performed on 32 cases of small cell neuroendocrine carcinoma of the bladder. Staining was scored for intensity (0: No staining; 1: Weak; 2: Moderate; 3: Strong) and proportion of cells stained (0: 0%; 1: >0% to ≤25%; 2: >25% to ≤50%; 3: >50% to ≤75%; 4: >75% to 100%). INSM1 was positive (intensity 1 to 3 or proportion 1 to 4) in 87% (28/32) of cases (20 with intensity 2 to 3, 17 with proportion 3 to 4). CD56, synaptophysin, and chromogranin were positive in 75% (24/32), 60% (19/32), and 44% (14/32) of cases, respectively. INSM1 was negative (n=4) or only showed weak intensity staining (n=7) in 34% (11/32) of cases. INSM1 is a sensitive marker of small cell neuroendocrine differentiation of the urinary tract. However, this study suggests that optimal utilization of INSM1 would be inclusion in a limited panel of stains rather than as a stand-alone screening marker given that it is negative or only shows weak intensity staining in a significant proportion of cases.

AB - Clinical guidelines state that neoadjuvant chemotherapy should be administered before surgery in muscle invasive urinary bladder small cell neuroendocrine carcinoma. Recently described marker insulinoma-associated protein 1 (INSM1) has been reported to be sensitive and specific for neuroendocrine differentiation, however, its efficacy in urinary tract small cell carcinoma is not well established. This study examines immunohistochemical expression of INSM1 on whole tissue sections of urinary tract small cell neuroendocrine carcinoma and compares INSM1 expression with established neuroendocrine markers. Immunohistochemical stains for CD56, INSM1, synaptophysin, and chromogranin were performed on 32 cases of small cell neuroendocrine carcinoma of the bladder. Staining was scored for intensity (0: No staining; 1: Weak; 2: Moderate; 3: Strong) and proportion of cells stained (0: 0%; 1: >0% to ≤25%; 2: >25% to ≤50%; 3: >50% to ≤75%; 4: >75% to 100%). INSM1 was positive (intensity 1 to 3 or proportion 1 to 4) in 87% (28/32) of cases (20 with intensity 2 to 3, 17 with proportion 3 to 4). CD56, synaptophysin, and chromogranin were positive in 75% (24/32), 60% (19/32), and 44% (14/32) of cases, respectively. INSM1 was negative (n=4) or only showed weak intensity staining (n=7) in 34% (11/32) of cases. INSM1 is a sensitive marker of small cell neuroendocrine differentiation of the urinary tract. However, this study suggests that optimal utilization of INSM1 would be inclusion in a limited panel of stains rather than as a stand-alone screening marker given that it is negative or only shows weak intensity staining in a significant proportion of cases.

KW - bladder

KW - INSM1

KW - neuroendocrine

KW - small cell

KW - urinary bladder

UR - http://www.scopus.com/inward/record.url?scp=85077732296&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85077732296&partnerID=8YFLogxK

U2 - 10.1097/PAI.0000000000000824

DO - 10.1097/PAI.0000000000000824

M3 - Article

C2 - 31876605

AN - SCOPUS:85077732296

JO - Applied Immunohistochemistry and Molecular Morphology

JF - Applied Immunohistochemistry and Molecular Morphology

SN - 1541-2016

ER -