Concordance of genetic alterations in poorly differentiated colorectal neuroendocrine carcinomas and associated adenocarcinomas

Alexander Vortmeyer, Irina A. Lubensky, Maria J. Merino, Chao Yu Wang, Tina Pham, Emma E. Furth, Zhengping Zhuang

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Background: The histopathologic spectrum of colorectal neuroendocrine tumors ranges from benign to highly malignant. In this spectrum, poorly differentiated neuroendocrine carcinoma (PDNC) is the most aggressive type, characterized by early dissemination and a rapidly fatal course. Since it is unclear whether PDNC originates from neoplastic transformation of preexisting neuroectodermal cells, pluripotent epithelial stem cells, or adenocarcinoma precursor cells, we investigated the histogenesis of this type of cancer by performing genetic analyses on a series of colorectal tumors. Methods: Archived histologic sections of colorectal PDNC from nine patients were analyzed; gastrointestinal carcinoid tumor specimens from four patients were used as controls. The specimens were deparaffinized, microdissected, and analyzed genetically. After DNA extraction, polymerase chain reaction amplification was performed to investigate alteration (i.e., loss of heterozygosity [LOH]) of the APC (adenomatous polyposis coli), DCC (deleted in colorectal carcinoma), and p53 (also known as TP53) genes. Results: LOH of the APC, DCC, or p53 genes was observed in six of eight informative PDNC tumors; no LOH was detected in the carcinoid control specimens. Four of five informative PDNC tumors had associated adenocarcinoma; LOH of the APC and p53 genes in these tumors involved the same allele in both tissue components. Four of the five tumors with associated adenocarcinoma showed LOH of the DCC gene; in three of these four tumors, the PDNC and adenomatous components showed LOH of the same allele. Conclusions: PDNC and associated adenocarcinoma appear to be derived from the same cell of origin, which is most likely either a pluripotent epithelial stem cell or an adenocarcinoma precursor cell.

Original languageEnglish (US)
Pages (from-to)1448-1453
Number of pages6
JournalJournal of the National Cancer Institute
Volume89
Issue number19
DOIs
StatePublished - Oct 1 1997
Externally publishedYes

Fingerprint

Neuroendocrine Carcinoma
Loss of Heterozygosity
Colorectal Neoplasms
Adenocarcinoma
Neuroendocrine Tumors
p53 Genes
Pluripotent Stem Cells
Adenomatous Polyposis Coli
Carcinoid Tumor
Neoplasms
Epithelial Cells
Alleles
APC Genes
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Concordance of genetic alterations in poorly differentiated colorectal neuroendocrine carcinomas and associated adenocarcinomas. / Vortmeyer, Alexander; Lubensky, Irina A.; Merino, Maria J.; Wang, Chao Yu; Pham, Tina; Furth, Emma E.; Zhuang, Zhengping.

In: Journal of the National Cancer Institute, Vol. 89, No. 19, 01.10.1997, p. 1448-1453.

Research output: Contribution to journalArticle

Vortmeyer, Alexander ; Lubensky, Irina A. ; Merino, Maria J. ; Wang, Chao Yu ; Pham, Tina ; Furth, Emma E. ; Zhuang, Zhengping. / Concordance of genetic alterations in poorly differentiated colorectal neuroendocrine carcinomas and associated adenocarcinomas. In: Journal of the National Cancer Institute. 1997 ; Vol. 89, No. 19. pp. 1448-1453.
@article{037a491fe3634573bf8d361f57a94ced,
title = "Concordance of genetic alterations in poorly differentiated colorectal neuroendocrine carcinomas and associated adenocarcinomas",
abstract = "Background: The histopathologic spectrum of colorectal neuroendocrine tumors ranges from benign to highly malignant. In this spectrum, poorly differentiated neuroendocrine carcinoma (PDNC) is the most aggressive type, characterized by early dissemination and a rapidly fatal course. Since it is unclear whether PDNC originates from neoplastic transformation of preexisting neuroectodermal cells, pluripotent epithelial stem cells, or adenocarcinoma precursor cells, we investigated the histogenesis of this type of cancer by performing genetic analyses on a series of colorectal tumors. Methods: Archived histologic sections of colorectal PDNC from nine patients were analyzed; gastrointestinal carcinoid tumor specimens from four patients were used as controls. The specimens were deparaffinized, microdissected, and analyzed genetically. After DNA extraction, polymerase chain reaction amplification was performed to investigate alteration (i.e., loss of heterozygosity [LOH]) of the APC (adenomatous polyposis coli), DCC (deleted in colorectal carcinoma), and p53 (also known as TP53) genes. Results: LOH of the APC, DCC, or p53 genes was observed in six of eight informative PDNC tumors; no LOH was detected in the carcinoid control specimens. Four of five informative PDNC tumors had associated adenocarcinoma; LOH of the APC and p53 genes in these tumors involved the same allele in both tissue components. Four of the five tumors with associated adenocarcinoma showed LOH of the DCC gene; in three of these four tumors, the PDNC and adenomatous components showed LOH of the same allele. Conclusions: PDNC and associated adenocarcinoma appear to be derived from the same cell of origin, which is most likely either a pluripotent epithelial stem cell or an adenocarcinoma precursor cell.",
author = "Alexander Vortmeyer and Lubensky, {Irina A.} and Merino, {Maria J.} and Wang, {Chao Yu} and Tina Pham and Furth, {Emma E.} and Zhengping Zhuang",
year = "1997",
month = "10",
day = "1",
doi = "10.1093/jnci/89.19.1448",
language = "English (US)",
volume = "89",
pages = "1448--1453",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "19",

}

TY - JOUR

T1 - Concordance of genetic alterations in poorly differentiated colorectal neuroendocrine carcinomas and associated adenocarcinomas

AU - Vortmeyer, Alexander

AU - Lubensky, Irina A.

AU - Merino, Maria J.

AU - Wang, Chao Yu

AU - Pham, Tina

AU - Furth, Emma E.

AU - Zhuang, Zhengping

PY - 1997/10/1

Y1 - 1997/10/1

N2 - Background: The histopathologic spectrum of colorectal neuroendocrine tumors ranges from benign to highly malignant. In this spectrum, poorly differentiated neuroendocrine carcinoma (PDNC) is the most aggressive type, characterized by early dissemination and a rapidly fatal course. Since it is unclear whether PDNC originates from neoplastic transformation of preexisting neuroectodermal cells, pluripotent epithelial stem cells, or adenocarcinoma precursor cells, we investigated the histogenesis of this type of cancer by performing genetic analyses on a series of colorectal tumors. Methods: Archived histologic sections of colorectal PDNC from nine patients were analyzed; gastrointestinal carcinoid tumor specimens from four patients were used as controls. The specimens were deparaffinized, microdissected, and analyzed genetically. After DNA extraction, polymerase chain reaction amplification was performed to investigate alteration (i.e., loss of heterozygosity [LOH]) of the APC (adenomatous polyposis coli), DCC (deleted in colorectal carcinoma), and p53 (also known as TP53) genes. Results: LOH of the APC, DCC, or p53 genes was observed in six of eight informative PDNC tumors; no LOH was detected in the carcinoid control specimens. Four of five informative PDNC tumors had associated adenocarcinoma; LOH of the APC and p53 genes in these tumors involved the same allele in both tissue components. Four of the five tumors with associated adenocarcinoma showed LOH of the DCC gene; in three of these four tumors, the PDNC and adenomatous components showed LOH of the same allele. Conclusions: PDNC and associated adenocarcinoma appear to be derived from the same cell of origin, which is most likely either a pluripotent epithelial stem cell or an adenocarcinoma precursor cell.

AB - Background: The histopathologic spectrum of colorectal neuroendocrine tumors ranges from benign to highly malignant. In this spectrum, poorly differentiated neuroendocrine carcinoma (PDNC) is the most aggressive type, characterized by early dissemination and a rapidly fatal course. Since it is unclear whether PDNC originates from neoplastic transformation of preexisting neuroectodermal cells, pluripotent epithelial stem cells, or adenocarcinoma precursor cells, we investigated the histogenesis of this type of cancer by performing genetic analyses on a series of colorectal tumors. Methods: Archived histologic sections of colorectal PDNC from nine patients were analyzed; gastrointestinal carcinoid tumor specimens from four patients were used as controls. The specimens were deparaffinized, microdissected, and analyzed genetically. After DNA extraction, polymerase chain reaction amplification was performed to investigate alteration (i.e., loss of heterozygosity [LOH]) of the APC (adenomatous polyposis coli), DCC (deleted in colorectal carcinoma), and p53 (also known as TP53) genes. Results: LOH of the APC, DCC, or p53 genes was observed in six of eight informative PDNC tumors; no LOH was detected in the carcinoid control specimens. Four of five informative PDNC tumors had associated adenocarcinoma; LOH of the APC and p53 genes in these tumors involved the same allele in both tissue components. Four of the five tumors with associated adenocarcinoma showed LOH of the DCC gene; in three of these four tumors, the PDNC and adenomatous components showed LOH of the same allele. Conclusions: PDNC and associated adenocarcinoma appear to be derived from the same cell of origin, which is most likely either a pluripotent epithelial stem cell or an adenocarcinoma precursor cell.

UR - http://www.scopus.com/inward/record.url?scp=0030882999&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030882999&partnerID=8YFLogxK

U2 - 10.1093/jnci/89.19.1448

DO - 10.1093/jnci/89.19.1448

M3 - Article

C2 - 9326914

AN - SCOPUS:0030882999

VL - 89

SP - 1448

EP - 1453

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 19

ER -