Anaplastic lymphoma kinase gene copy number gain in inflammatory breast cancer (IBC): Prevalence, clinicopathologic features and prognostic implication

Min Hwan Kim, Soohyeon Lee, Ja Seung Koo, Kyung Hae Jung, In Hae Park, Joon Jeong, Seung Il Kim, Seho Park, Hyung Seok Park, Byeong Woo Park, Joo Hang Kim, Joohyuk Sohn

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, and its molecular pathogenesis still remains to be elucidated. This study aimed to evaluate the prevalence and implication of anaplastic lymphoma kinase (ALK) copy number change in IBC patients. Methods We retrospectively collected formalin-fixed, paraffin-embedded tumor tissues and medical records of IBC patients from several institutes in Korea. ALK gene copy number change and rearrangement were assessed by fluorescence in situ hybridization (FISH) assay, and ALK expression status was evaluated by immunohistochemical (IHC) staining. Results Thirty-six IBC patients including those with HER2 (+) breast cancer (16/36, 44.4%) and triple-negative breast cancer (13/36, 36.1%) were enrolled in this study. ALK copy number gain (CNG) was observed in 47.2% (17/36) of patients, including one patient who harbored ALK gene amplification. ALK CNG (+) patients showed significantly worse overall survival compared to ALK CNG (-) patients in univariate analysis (24.9 months vs. 38.1 months, p = 0.033). Recurrence free survival (RFS) after curative mastectomy was also significantly shorter in ALK CNG (+) patients than in ALK CNG (-) patients (n = 22, 12.7 months vs. 43.3 months, p = 0.016). Multivariate Cox regression analysis with adjustment for HER2 and ER statuses showed significantly poorer RFS for ALK CNG (+) patients (HR 5.63, 95% CI 1.11- 28.44, p = 0.037). Conclusion This study shows a significant presence of ALK CNG in IBC patients, and ALK CNG was associated with significantly poorer RFS.

Original languageEnglish
Article numbere0120320
JournalPloS one
Volume10
Issue number3
DOIs
Publication statusPublished - 2015 Mar 24

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Inflammatory Breast Neoplasms
gene dosage
Gene Dosage
lymphoma
breast neoplasms
phosphotransferases (kinases)
Genes
Survival
Recurrence
anaplastic lymphoma kinase
Triple Negative Breast Neoplasms
Breast Neoplasms
Gene Amplification
Mastectomy
Korea
fluorescence in situ hybridization
Fluorescence In Situ Hybridization
formalin
Regression analysis
Paraffin

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Kim, Min Hwan ; Lee, Soohyeon ; Koo, Ja Seung ; Jung, Kyung Hae ; Park, In Hae ; Jeong, Joon ; Kim, Seung Il ; Park, Seho ; Park, Hyung Seok ; Park, Byeong Woo ; Kim, Joo Hang ; Sohn, Joohyuk. / Anaplastic lymphoma kinase gene copy number gain in inflammatory breast cancer (IBC) : Prevalence, clinicopathologic features and prognostic implication. In: PloS one. 2015 ; Vol. 10, No. 3.
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abstract = "Background Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, and its molecular pathogenesis still remains to be elucidated. This study aimed to evaluate the prevalence and implication of anaplastic lymphoma kinase (ALK) copy number change in IBC patients. Methods We retrospectively collected formalin-fixed, paraffin-embedded tumor tissues and medical records of IBC patients from several institutes in Korea. ALK gene copy number change and rearrangement were assessed by fluorescence in situ hybridization (FISH) assay, and ALK expression status was evaluated by immunohistochemical (IHC) staining. Results Thirty-six IBC patients including those with HER2 (+) breast cancer (16/36, 44.4{\%}) and triple-negative breast cancer (13/36, 36.1{\%}) were enrolled in this study. ALK copy number gain (CNG) was observed in 47.2{\%} (17/36) of patients, including one patient who harbored ALK gene amplification. ALK CNG (+) patients showed significantly worse overall survival compared to ALK CNG (-) patients in univariate analysis (24.9 months vs. 38.1 months, p = 0.033). Recurrence free survival (RFS) after curative mastectomy was also significantly shorter in ALK CNG (+) patients than in ALK CNG (-) patients (n = 22, 12.7 months vs. 43.3 months, p = 0.016). Multivariate Cox regression analysis with adjustment for HER2 and ER statuses showed significantly poorer RFS for ALK CNG (+) patients (HR 5.63, 95{\%} CI 1.11- 28.44, p = 0.037). Conclusion This study shows a significant presence of ALK CNG in IBC patients, and ALK CNG was associated with significantly poorer RFS.",
author = "Kim, {Min Hwan} and Soohyeon Lee and Koo, {Ja Seung} and Jung, {Kyung Hae} and Park, {In Hae} and Joon Jeong and Kim, {Seung Il} and Seho Park and Park, {Hyung Seok} and Park, {Byeong Woo} and Kim, {Joo Hang} and Joohyuk Sohn",
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Anaplastic lymphoma kinase gene copy number gain in inflammatory breast cancer (IBC) : Prevalence, clinicopathologic features and prognostic implication. / Kim, Min Hwan; Lee, Soohyeon; Koo, Ja Seung; Jung, Kyung Hae; Park, In Hae; Jeong, Joon; Kim, Seung Il; Park, Seho; Park, Hyung Seok; Park, Byeong Woo; Kim, Joo Hang; Sohn, Joohyuk.

In: PloS one, Vol. 10, No. 3, e0120320, 24.03.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Anaplastic lymphoma kinase gene copy number gain in inflammatory breast cancer (IBC)

T2 - Prevalence, clinicopathologic features and prognostic implication

AU - Kim, Min Hwan

AU - Lee, Soohyeon

AU - Koo, Ja Seung

AU - Jung, Kyung Hae

AU - Park, In Hae

AU - Jeong, Joon

AU - Kim, Seung Il

AU - Park, Seho

AU - Park, Hyung Seok

AU - Park, Byeong Woo

AU - Kim, Joo Hang

AU - Sohn, Joohyuk

PY - 2015/3/24

Y1 - 2015/3/24

N2 - Background Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, and its molecular pathogenesis still remains to be elucidated. This study aimed to evaluate the prevalence and implication of anaplastic lymphoma kinase (ALK) copy number change in IBC patients. Methods We retrospectively collected formalin-fixed, paraffin-embedded tumor tissues and medical records of IBC patients from several institutes in Korea. ALK gene copy number change and rearrangement were assessed by fluorescence in situ hybridization (FISH) assay, and ALK expression status was evaluated by immunohistochemical (IHC) staining. Results Thirty-six IBC patients including those with HER2 (+) breast cancer (16/36, 44.4%) and triple-negative breast cancer (13/36, 36.1%) were enrolled in this study. ALK copy number gain (CNG) was observed in 47.2% (17/36) of patients, including one patient who harbored ALK gene amplification. ALK CNG (+) patients showed significantly worse overall survival compared to ALK CNG (-) patients in univariate analysis (24.9 months vs. 38.1 months, p = 0.033). Recurrence free survival (RFS) after curative mastectomy was also significantly shorter in ALK CNG (+) patients than in ALK CNG (-) patients (n = 22, 12.7 months vs. 43.3 months, p = 0.016). Multivariate Cox regression analysis with adjustment for HER2 and ER statuses showed significantly poorer RFS for ALK CNG (+) patients (HR 5.63, 95% CI 1.11- 28.44, p = 0.037). Conclusion This study shows a significant presence of ALK CNG in IBC patients, and ALK CNG was associated with significantly poorer RFS.

AB - Background Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, and its molecular pathogenesis still remains to be elucidated. This study aimed to evaluate the prevalence and implication of anaplastic lymphoma kinase (ALK) copy number change in IBC patients. Methods We retrospectively collected formalin-fixed, paraffin-embedded tumor tissues and medical records of IBC patients from several institutes in Korea. ALK gene copy number change and rearrangement were assessed by fluorescence in situ hybridization (FISH) assay, and ALK expression status was evaluated by immunohistochemical (IHC) staining. Results Thirty-six IBC patients including those with HER2 (+) breast cancer (16/36, 44.4%) and triple-negative breast cancer (13/36, 36.1%) were enrolled in this study. ALK copy number gain (CNG) was observed in 47.2% (17/36) of patients, including one patient who harbored ALK gene amplification. ALK CNG (+) patients showed significantly worse overall survival compared to ALK CNG (-) patients in univariate analysis (24.9 months vs. 38.1 months, p = 0.033). Recurrence free survival (RFS) after curative mastectomy was also significantly shorter in ALK CNG (+) patients than in ALK CNG (-) patients (n = 22, 12.7 months vs. 43.3 months, p = 0.016). Multivariate Cox regression analysis with adjustment for HER2 and ER statuses showed significantly poorer RFS for ALK CNG (+) patients (HR 5.63, 95% CI 1.11- 28.44, p = 0.037). Conclusion This study shows a significant presence of ALK CNG in IBC patients, and ALK CNG was associated with significantly poorer RFS.

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