title: Immunolocalization of thymidylate synthase as a favorable prognostic marker in estrogen receptor-positive breast carcinoma.
abstract: BACKGROUND
  Thymidylate synthase (TS) is an enzyme involved in DNA synthesis, and it is a target for 5-fluorouracil. Previous studies have demonstrated that TS is a potent estrogen-induced gene in breast carcinoma cells, suggesting the importance of TS in estrogen-receptor (ER)-positive breast carcinoma. TS immunolocalization has been reported previously, but the clinicopathological significance of TS in ER-positive breast carcinoma still remains unclear.
  
  
  METHODS
  We immunolocalized TS in 178 breast carcinoma tissues in total, and examined its significance according to the ER-status.
  
  
  RESULTS
  TS status was positive in 58% of ER-positive ductal carcinoma in situ (DCIS) cases, and it was significantly associated with the Ki-67 and progesterone receptor (PR). Moreover, in ER-positive DCIS patients who received aromatase inhibitor (AI) before surgery, TS immunoreactivity was significantly decreased after AI treatment. In ER-positive invasive ductal carcinoma (IDC) cases, TS status was significantly associated with PR, and it turned out an independent favorable prognostic factor for recurrence of the patients by multivariate analysis. On the other hand, TS status was positively correlated with pathological T factor in ER-negative IDC cases, and tended to have a worse prognosis for disease-free survival of the patients.
  
  
  CONCLUSIONS
  These results suggest that TS expression is mainly regulated by estrogen in ER-positive breast carcinoma and is associated with estrogen-mediated proliferation. TS status is a favorable prognostic factor in ER-positive IDC patients, which is different from the ER-negative cases.
authors: Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan. k-takagi@med.tohoku.ac.jp.
authors: Kiyoshi
authors: K
authors: Takagi
authors: Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Yasuhiro
authors: Y
authors: Miki
authors: Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Yasuhiro
authors: Y
authors: Nakamura
authors: Department of Surgery, Tohoku Kosai Hospital, Sendai, Japan.
authors: Hisashi
authors: H
authors: Hirakawa
authors: Department of Breast Oncology, Miyagi Cancer Center Hospital, Natori, Japan.
authors: Yoichiro
authors: Y
authors: Kakugawa
authors: Department of Surgery, Nihonkai General Hospital, Sakata, Japan.
authors: Goro
authors: G
authors: Amano
authors: Department of Pathology, Tohoku University Hospital, Sendai, Japan.
authors: Mika
authors: M
authors: Watanabe
authors: Department of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Takanori
authors: T
authors: Ishida
authors: Department of Anatomic Pathology, Tohoku University Graduate School of Medicine and Department of Pathology, Tohoku University Hospital, Sendai, Japan.
authors: Hironobu
authors: H
authors: Sasano
authors: Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Takashi
authors: T
authors: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D013940:Thymidylate Synthase