Nodal metastasis signatures in breast cancer

Kyeongmee Park, Joo Hyun Lee, Hyun Ho Han, Seong Gyeong Mun, Suki Kang, Youn Jin Cha, Ja Seung Koo, Min Ju Kim, Hye Sun Lee, Jieun Moon, Nam Hoon Cho

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Although the molecular taxonomy of invasive breast cancer is based on heterogeneous histologic types, pathologic nodal (pN) stage remains one of the most important independent prognostic factors. Although node-positive number (NPN) has been widely as an accepted staging algorithm of pN stage, the node-positive ratio (NPR) in totally resected axillary nodes has been considered as another reasonable indicator. We aimed to identify signatures to play a predictive role in nodal metastasis for analytic validation between the primary breast cancers with positive node metastasis and those with negative node metastasis. We validated expression profiles of surrogate candidates extracted from the prior 2D MALDI-TOF data for invasive breast cancer using fluorescence/silver in situ hybridization (FISH/SISH) and immunohistochemistry (IHC) in 151 primary breast cancers accompanied with 102 metastatic nodal tissues. Cox proportional hazards regression analyses indicated that event factors (recurrence or metastasis) were significantly more frequent in cases with CCDN1, c-myc gene amplification, IgHA2 low expression. CCDN1 gene amplification (OR: 5.702, p = 0.0006), IgHA2 low expression (OR: 0.16, p = 0.0184) remained significant factors for events on multivariate analyses. WDR + /ERK ++ was significantly detected in higher pN stage (averaging 6.5 regional nodes or 43% of NPR), while seldom found in pN0-1. In conclusion, both overexpression of WDR1 and p-ERK in the primary breast cancer could play a role in the nodal signature over pN2-3.

Original languageEnglish
Pages (from-to)680-687
Number of pages8
JournalPathology Research and Practice
Volume213
Issue number6
DOIs
Publication statusPublished - 2017 Jun

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Breast Neoplasms
Neoplasm Metastasis
Gene Amplification
myc Genes
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Fluorescence In Situ Hybridization
Silver
Multivariate Analysis
Immunohistochemistry
Regression Analysis
Recurrence

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Cell Biology

Cite this

Park, K., Lee, J. H., Han, H. H., Mun, S. G., Kang, S., Cha, Y. J., ... Cho, N. H. (2017). Nodal metastasis signatures in breast cancer. Pathology Research and Practice, 213(6), 680-687. https://doi.org/10.1016/j.prp.2016.11.017
Park, Kyeongmee ; Lee, Joo Hyun ; Han, Hyun Ho ; Mun, Seong Gyeong ; Kang, Suki ; Cha, Youn Jin ; Koo, Ja Seung ; Kim, Min Ju ; Lee, Hye Sun ; Moon, Jieun ; Cho, Nam Hoon. / Nodal metastasis signatures in breast cancer. In: Pathology Research and Practice. 2017 ; Vol. 213, No. 6. pp. 680-687.
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Park, K, Lee, JH, Han, HH, Mun, SG, Kang, S, Cha, YJ, Koo, JS, Kim, MJ, Lee, HS, Moon, J & Cho, NH 2017, 'Nodal metastasis signatures in breast cancer', Pathology Research and Practice, vol. 213, no. 6, pp. 680-687. https://doi.org/10.1016/j.prp.2016.11.017

Nodal metastasis signatures in breast cancer. / Park, Kyeongmee; Lee, Joo Hyun; Han, Hyun Ho; Mun, Seong Gyeong; Kang, Suki; Cha, Youn Jin; Koo, Ja Seung; Kim, Min Ju; Lee, Hye Sun; Moon, Jieun; Cho, Nam Hoon.

In: Pathology Research and Practice, Vol. 213, No. 6, 06.2017, p. 680-687.

Research output: Contribution to journalArticle

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T1 - Nodal metastasis signatures in breast cancer

AU - Park, Kyeongmee

AU - Lee, Joo Hyun

AU - Han, Hyun Ho

AU - Mun, Seong Gyeong

AU - Kang, Suki

AU - Cha, Youn Jin

AU - Koo, Ja Seung

AU - Kim, Min Ju

AU - Lee, Hye Sun

AU - Moon, Jieun

AU - Cho, Nam Hoon

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N2 - Although the molecular taxonomy of invasive breast cancer is based on heterogeneous histologic types, pathologic nodal (pN) stage remains one of the most important independent prognostic factors. Although node-positive number (NPN) has been widely as an accepted staging algorithm of pN stage, the node-positive ratio (NPR) in totally resected axillary nodes has been considered as another reasonable indicator. We aimed to identify signatures to play a predictive role in nodal metastasis for analytic validation between the primary breast cancers with positive node metastasis and those with negative node metastasis. We validated expression profiles of surrogate candidates extracted from the prior 2D MALDI-TOF data for invasive breast cancer using fluorescence/silver in situ hybridization (FISH/SISH) and immunohistochemistry (IHC) in 151 primary breast cancers accompanied with 102 metastatic nodal tissues. Cox proportional hazards regression analyses indicated that event factors (recurrence or metastasis) were significantly more frequent in cases with CCDN1, c-myc gene amplification, IgHA2 low expression. CCDN1 gene amplification (OR: 5.702, p = 0.0006), IgHA2 low expression (OR: 0.16, p = 0.0184) remained significant factors for events on multivariate analyses. WDR + /ERK ++ was significantly detected in higher pN stage (averaging 6.5 regional nodes or 43% of NPR), while seldom found in pN0-1. In conclusion, both overexpression of WDR1 and p-ERK in the primary breast cancer could play a role in the nodal signature over pN2-3.

AB - Although the molecular taxonomy of invasive breast cancer is based on heterogeneous histologic types, pathologic nodal (pN) stage remains one of the most important independent prognostic factors. Although node-positive number (NPN) has been widely as an accepted staging algorithm of pN stage, the node-positive ratio (NPR) in totally resected axillary nodes has been considered as another reasonable indicator. We aimed to identify signatures to play a predictive role in nodal metastasis for analytic validation between the primary breast cancers with positive node metastasis and those with negative node metastasis. We validated expression profiles of surrogate candidates extracted from the prior 2D MALDI-TOF data for invasive breast cancer using fluorescence/silver in situ hybridization (FISH/SISH) and immunohistochemistry (IHC) in 151 primary breast cancers accompanied with 102 metastatic nodal tissues. Cox proportional hazards regression analyses indicated that event factors (recurrence or metastasis) were significantly more frequent in cases with CCDN1, c-myc gene amplification, IgHA2 low expression. CCDN1 gene amplification (OR: 5.702, p = 0.0006), IgHA2 low expression (OR: 0.16, p = 0.0184) remained significant factors for events on multivariate analyses. WDR + /ERK ++ was significantly detected in higher pN stage (averaging 6.5 regional nodes or 43% of NPR), while seldom found in pN0-1. In conclusion, both overexpression of WDR1 and p-ERK in the primary breast cancer could play a role in the nodal signature over pN2-3.

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Park K, Lee JH, Han HH, Mun SG, Kang S, Cha YJ et al. Nodal metastasis signatures in breast cancer. Pathology Research and Practice. 2017 Jun;213(6):680-687. https://doi.org/10.1016/j.prp.2016.11.017