Clonality analysis of multifocal ipsilateral breast carcinomas using X-chromosome inactivation patterns

Hayeon Kim, Chung Yeul Kim, Kyong Hwa Park, Aeree Kim

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The definition of multifocal breast cancer is ambiguous, and its incidence varies depending on the definition and detection methods. Multifocal breast cancers either have the same clonal origin or arise from completely distinct progenitor cells. The current American Joint Committee on Cancer Staging system and College of American Pathologists breast tumor guidelines state that only the largest tumor needs to be staged and studied immunohistochemically, on the assumption that they are of the same origin. However, some multifocal tumors have been proved to have arisen from different clones. In the present study, 71 cases of surgically resected multifocal breast cancers were selected. To detect and characterize the tumors of each clonal origin, a human androgen receptor gene (HUMARA) assay to compare the X-chromosome inactivation patterns of multiple tumors was conducted. Twenty-nine of 71 (40.8%) patients were revealed to be heterozygous for HUMARA. Sixty-four (90.1%) patients had the same X chromosome inactivated in different tumors. Seven (9.9%) cases had different inactivated X chromosomes between multifocal tumors, indicating that those tumors were from separate progenitor cells. Five (7.0%) cases showed identical histologic features but had different inactivated HUMARA alleles. According to these results, 2 separate tumors might be synchronous primary tumors, although their histopathologic characteristics are similar. Furthermore, multifocal tumors can be of different origins despite being closely located to each other. These findings suggest that separate grouping of multiple breast tumors based on their clonal origin is needed for future studies.

Original languageEnglish
Pages (from-to)106-114
Number of pages9
JournalHuman Pathology
Volume78
DOIs
Publication statusPublished - 2018 Aug 1

Fingerprint

X Chromosome Inactivation
Breast Neoplasms
Neoplasms
X Chromosome
Stem Cells
Neoplasm Staging
Clone Cells
Alleles
Guidelines

Keywords

  • Breast neoplasm
  • Clonality analysis
  • HUMARA assay
  • Multifocal tumor
  • Multiple tumor

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Clonality analysis of multifocal ipsilateral breast carcinomas using X-chromosome inactivation patterns. / Kim, Hayeon; Kim, Chung Yeul; Park, Kyong Hwa; Kim, Aeree.

In: Human Pathology, Vol. 78, 01.08.2018, p. 106-114.

Research output: Contribution to journalArticle

@article{60d818b1de89452a8885fc24b08ecda6,
title = "Clonality analysis of multifocal ipsilateral breast carcinomas using X-chromosome inactivation patterns",
abstract = "The definition of multifocal breast cancer is ambiguous, and its incidence varies depending on the definition and detection methods. Multifocal breast cancers either have the same clonal origin or arise from completely distinct progenitor cells. The current American Joint Committee on Cancer Staging system and College of American Pathologists breast tumor guidelines state that only the largest tumor needs to be staged and studied immunohistochemically, on the assumption that they are of the same origin. However, some multifocal tumors have been proved to have arisen from different clones. In the present study, 71 cases of surgically resected multifocal breast cancers were selected. To detect and characterize the tumors of each clonal origin, a human androgen receptor gene (HUMARA) assay to compare the X-chromosome inactivation patterns of multiple tumors was conducted. Twenty-nine of 71 (40.8{\%}) patients were revealed to be heterozygous for HUMARA. Sixty-four (90.1{\%}) patients had the same X chromosome inactivated in different tumors. Seven (9.9{\%}) cases had different inactivated X chromosomes between multifocal tumors, indicating that those tumors were from separate progenitor cells. Five (7.0{\%}) cases showed identical histologic features but had different inactivated HUMARA alleles. According to these results, 2 separate tumors might be synchronous primary tumors, although their histopathologic characteristics are similar. Furthermore, multifocal tumors can be of different origins despite being closely located to each other. These findings suggest that separate grouping of multiple breast tumors based on their clonal origin is needed for future studies.",
keywords = "Breast neoplasm, Clonality analysis, HUMARA assay, Multifocal tumor, Multiple tumor",
author = "Hayeon Kim and Kim, {Chung Yeul} and Park, {Kyong Hwa} and Aeree Kim",
year = "2018",
month = "8",
day = "1",
doi = "10.1016/j.humpath.2018.04.016",
language = "English",
volume = "78",
pages = "106--114",
journal = "Human Pathology",
issn = "0046-8177",
publisher = "W.B. Saunders Ltd",

}

TY - JOUR

T1 - Clonality analysis of multifocal ipsilateral breast carcinomas using X-chromosome inactivation patterns

AU - Kim, Hayeon

AU - Kim, Chung Yeul

AU - Park, Kyong Hwa

AU - Kim, Aeree

PY - 2018/8/1

Y1 - 2018/8/1

N2 - The definition of multifocal breast cancer is ambiguous, and its incidence varies depending on the definition and detection methods. Multifocal breast cancers either have the same clonal origin or arise from completely distinct progenitor cells. The current American Joint Committee on Cancer Staging system and College of American Pathologists breast tumor guidelines state that only the largest tumor needs to be staged and studied immunohistochemically, on the assumption that they are of the same origin. However, some multifocal tumors have been proved to have arisen from different clones. In the present study, 71 cases of surgically resected multifocal breast cancers were selected. To detect and characterize the tumors of each clonal origin, a human androgen receptor gene (HUMARA) assay to compare the X-chromosome inactivation patterns of multiple tumors was conducted. Twenty-nine of 71 (40.8%) patients were revealed to be heterozygous for HUMARA. Sixty-four (90.1%) patients had the same X chromosome inactivated in different tumors. Seven (9.9%) cases had different inactivated X chromosomes between multifocal tumors, indicating that those tumors were from separate progenitor cells. Five (7.0%) cases showed identical histologic features but had different inactivated HUMARA alleles. According to these results, 2 separate tumors might be synchronous primary tumors, although their histopathologic characteristics are similar. Furthermore, multifocal tumors can be of different origins despite being closely located to each other. These findings suggest that separate grouping of multiple breast tumors based on their clonal origin is needed for future studies.

AB - The definition of multifocal breast cancer is ambiguous, and its incidence varies depending on the definition and detection methods. Multifocal breast cancers either have the same clonal origin or arise from completely distinct progenitor cells. The current American Joint Committee on Cancer Staging system and College of American Pathologists breast tumor guidelines state that only the largest tumor needs to be staged and studied immunohistochemically, on the assumption that they are of the same origin. However, some multifocal tumors have been proved to have arisen from different clones. In the present study, 71 cases of surgically resected multifocal breast cancers were selected. To detect and characterize the tumors of each clonal origin, a human androgen receptor gene (HUMARA) assay to compare the X-chromosome inactivation patterns of multiple tumors was conducted. Twenty-nine of 71 (40.8%) patients were revealed to be heterozygous for HUMARA. Sixty-four (90.1%) patients had the same X chromosome inactivated in different tumors. Seven (9.9%) cases had different inactivated X chromosomes between multifocal tumors, indicating that those tumors were from separate progenitor cells. Five (7.0%) cases showed identical histologic features but had different inactivated HUMARA alleles. According to these results, 2 separate tumors might be synchronous primary tumors, although their histopathologic characteristics are similar. Furthermore, multifocal tumors can be of different origins despite being closely located to each other. These findings suggest that separate grouping of multiple breast tumors based on their clonal origin is needed for future studies.

KW - Breast neoplasm

KW - Clonality analysis

KW - HUMARA assay

KW - Multifocal tumor

KW - Multiple tumor

UR - http://www.scopus.com/inward/record.url?scp=85048882542&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048882542&partnerID=8YFLogxK

U2 - 10.1016/j.humpath.2018.04.016

DO - 10.1016/j.humpath.2018.04.016

M3 - Article

C2 - 29727695

AN - SCOPUS:85048882542

VL - 78

SP - 106

EP - 114

JO - Human Pathology

JF - Human Pathology

SN - 0046-8177

ER -