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Breast Cancer Research

, 12:R100

First Online: 23 November 2010Received: 31 August 2010Revised: 20 October 2010Accepted: 23 November 2010


IntroductionThis study was aimed at understanding the clinicopathological significance of cystatin M loss, and investigating possible factors responsible for cystatin M loss in breast cancer.

MethodsThe expression of estrogen receptor ER, progesterone receptor PR, HER2, HER4, and cystatin M was retrospectively analyzed using immunohistochemistry in 117 patients with ductal carcinoma in situ DCIS and in 175 patients with invasive breast cancer IBC. The methylation status of CST6 gene encoding cystatin M was evaluated using methylation-specific polymerase chain reaction PCR in formalin-fixed paraffin-embedded tissues from 292 participants and using pyrosequencing in fresh-frozen tumor and matched normal tissues from 51 IBC patients.

ResultsCystatin M loss was found in 9 8% of 117 patients with DCIS and in 99 57% of 175 with invasive breast cancer IBC P < 0.0001. Cystatin M loss was found in 58 57% of 101 HER2-negative IBCs and in 41 55% of 74 HER2-positive IBCs, and this difference was not statistically significant P = 0.97. However, cystatin M loss was significantly associated with the loss of ER P = 0.01, PR P = 0.002, and HER4 P = 0.003 in IBCs. Cystatin M loss occurred in 34 76% of the 45 HER4-negative IBCs and in 65 50% of the 130 HER4-positive IBCs. Multivariate analysis showed that cystatin M loss occurred at a 3.57 times 95% CI = 1.28 to 9.98; P = 0.01 higher prevalence in the triple-negative IBCs of ER, PR, and HER4 than in other subtypes, after adjusting for age. The quantity of CST6 methylation was associated with ER loss P = 0.0002 in IBCs but not with the loss of PR P = 0.64 or HER4 P = 0.87.

ConclusionsThe present study suggests that cystatin M loss may be associated with the losses of ER, PR, and HER4 in IBC.

AbbreviationsDCISductal carcinoma in situ

ERestrogen receptor

EREestrogen response element

IBCinvasive breast cancer

ICDintracellular domain

ISimmunoreactive score


PBSphosphate-buffered saline

PCRpolymerase chain reaction

PRprogesterone receptor

SDF-1stromal cell-derived factor 1

STAT5Asignal transducer and activator of transcription 5A

TACETNFα-converting enzyme

TMAtissue microarray

TNBCsTriple-negative breast cancers


YAPYes-associated protein.

Electronic supplementary materialThe online version of this article doi:10.1186-bcr2783 contains supplementary material, which is available to authorized users.

Eunkyung Ko, Seong-Eun Park contributed equally to this work.

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Autor: Eunkyung Ko - Seong-Eun Park - Eun Yoon Cho - Yujin Kim - Jung-Ah Hwang - Yeon-Su Lee - Seok Jin Nam - Saik Bang - Jooba


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