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The methylation status of <jats:italic>CST6<\/jats:italic> 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.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Cystatin M loss was found in 9 (8%) of 117 patients with DCIS and in 99 (57%) of 175 with invasive breast cancer (IBC) (<jats:italic>P<\/jats:italic> &lt; 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 (<jats:italic>P<\/jats:italic> = 0.97). However, cystatin M loss was significantly associated with the loss of ER (<jats:italic>P<\/jats:italic> = 0.01), PR (<jats:italic>P<\/jats:italic> = 0.002), and HER4 (<jats:italic>P<\/jats:italic> = 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; <jats:italic>P<\/jats:italic> = 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 <jats:italic>CST6<\/jats:italic> methylation was associated with ER loss (<jats:italic>P<\/jats:italic> = 0.0002) in IBCs but not with the loss of PR (<jats:italic>P<\/jats:italic> = 0.64) or HER4 (<jats:italic>P<\/jats:italic> = 0.87).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>The present study suggests that cystatin M loss may be associated with the losses of ER, PR, and HER4 in IBC.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/bcr2783","type":"journal-article","created":{"date-parts":[[2010,11,23]],"date-time":"2010-11-23T19:14:20Z","timestamp":1290539660000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Cystatin M loss is associated with the losses of estrogen receptor, progesterone receptor, and HER4 in invasive breast cancer"],"prefix":"10.1186","volume":"12","author":[{"given":"Eunkyung","family":"Ko","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong-Eun","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Yoon","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Ah","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeon-Su","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seok Jin","family":"Nam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saik","family":"Bang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joobae","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duk-Hwan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2010,11,23]]},"reference":[{"key":"2762_CR1","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1093\/jnci\/94.20.1546","volume":"94","author":"VL Ernster","year":"2002","unstructured":"Ernster VL, Ballard-Barbash R, Barlow WE, Zheng Y, Weaver DL, Cutter G, Yankaskas BC, Rosenberg R, Carney PA, Kerlikowske K, Taplin SH, Urban N, Geller BM: Detection of ductal carcinoma in situ in women undergoing screening mammography. 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