title: Prognostic significance of mucin expression profiles in breast carcinoma with signet ring cells: a clinicopathological study.
abstract: BACKGROUND
  Signet ring cells (SRCs) often accompany gastrointestinal carcinoma, referred to as SRC carcinoma; however, breast cancers containing SRCs have not been well characterized, leaving the prognostic significance of SRCs undetermined. We have described clinicopathological characteristics of patients with breast cancer containing SRCs in relation to the expression levels of MUC1, MUC2, MUC4, MUC5AC, and MUC6.
  
  
  METHODS
  Twenty-two breast cancer cases with variable degrees of SRC population were retrospectively studied. Each case was categorized as high (>31 %) or low (<30 %) SRC tumor. The SRCs were morphologically classified into the intra-cytoplasmic lumen (ICL) type, or the non-ICL type. The expression levels of MUC1, MUC2, MUC4, MUC5AC and MUC6 were determined immunohistochemically. Depending on its subcellular localization, MUC1 was categorized as the luminal and cytoplasmic (LC) type, or the cytoplasmic with circumferential membranous accentuation (CM) type. These histological findings were compared with other clinicopathological parameters.
  
  
  RESULTS
  The series consisted of invasive ductal carcinoma (n = 9), invasive lobular carcinoma (n = 9), and mucinous carcinoma (n = 4) cases. The SRC population accounted for 8-81 % of the tumor cells. Eight cases had ICL type SRCs, and the remaining 14 had non-ICL type SRCs. Neither the high (n = 12) and low (n = 10) percentage of SRCs, nor the SRC types affected the clinicopathological parameters. In the low MUC1 group (n = 11), larger tumors, higher nuclear grade, lymph node metastasis, and negativity for estrogen receptor was more frequently identified compared to the high MUC1 group (n = 11; p = 0.01, p = 0.002, p = 0.008, and p = 0.02, respectively). The CM group (n = 7) had more patients with large-sized tumors, lymph node metastasis, lymphovascular invasion, and higher Ki67 indices than the LC group (n = 15; p = 0.04, p = 0.001, p = 0.006, and p = 0.03, respectively). The expression levels of MUC2, MUC4, MUC5AC, and MUC6 showed no clinicopathological significance. Two patients with low MUC1 expression and CM patterns had tumor recurrence, resulting in death, while all the other patients survived without recurrence.
  
  
  CONCLUSIONS
  Our results demonstrate that in breast cancers containing SRCs, low MUC1 expression and/or its CM subcellular localization patterns are associated with unfavorable clinicopathological factors. The utility of MUC1 expression as a prognostic marker remains to be verified in future studies.
authors.affiliation: Department of Diagnostic Pathology, Nippon Medical School Hospital, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. r-ohashi@nms.ac.jp.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Ohashi
authors.affiliation: Department of Diagnostic Pathology, Nippon Medical School Hospital, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Hayama
authors.affiliation: Department of Breast Surgery, Nippon Medical School Hospital, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: Department of Breast Surgery, Nippon Medical School Hospital, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Diagnostic Pathology, Nippon Medical School Hospital, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.|Department of Integrated Diagnostic Pathology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakatani
authors.affiliation: Department of Breast Surgery, Nippon Medical School Hospital, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takei
authors.affiliation: Department of Diagnostic Pathology, Nippon Medical School Hospital, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.|Department of Integrated Diagnostic Pathology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Zenya
authors.initials: Z
authors.lastname: Naito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018279:Carcinoma, Signet Ring Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009077:Mucins / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D009077:Mucins
keywords: Breast cancer; Mucin; Signet ring cells