title: The significance of combined CK5/6 and p63 immunohistochemistry in predicting the risks of subsequent carcinoma development in intraductal papilloma of the breast.
abstract: Prediction of subsequent risks of breast carcinoma (BC) development in intraductal papilloma (IDP) has remained controversial with the exception of atypical papilloma (AP). The potential value of immunohistochemistry (IHC) of cytokeratin 5/6 [CK5/6] and p63 have been proposed but its standardization has also remained controversial. We studied 17 patients initially diagnosed as IDP or AP who subsequently developed BC with 34 age-matched controls. We compared histological features, results of IHC (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2], p63, CK5/6, Ki67), and ultrasound findings. Univariate conditional logistic regression analysis revealed that the status of both CK5/6 and p63/CK5/6 were significantly associated with subsequent BC development (P < 0.05). BC development in CK5/6 positive patients was 17.9% and p63/CK5/6 double positive patients 8.6%, respectively. Ultrasound evaluation was not significantly associated with any of the parameters examined and subsequent carcinoma development. Despite CK5/6 positivity, the subsequent incidence of BC development was nearly 20%. However p63/CK5/6 double positive status could predict a significantly lower subsequent carcinoma incidence, indicating a more accurate prognostic utility. Combining p63/CK5/6 with histological findings could be easily applied and could predict the subsequent BC development of the patients diagnosed as IDP at biopsy.
authors.affiliation: Department of Pathology, St. Luke's International Hospital, Tokyo, Japan; Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Koyu
authors.initials: K
authors.lastname: Suzuki
authors.forename: Eriko
authors.initials: E
authors.lastname: Abe
authors.forename: Chihping
authors.initials: C
authors.lastname: Li
authors.forename: Mieko
authors.initials: M
authors.lastname: Uno
authors.forename: Futoshi
authors.initials: F
authors.lastname: Akiyama
authors.forename: Hideko
authors.initials: H
authors.lastname: Yamauchi
authors.forename: Mari
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ohde
authors.forename: Gautam
authors.initials: G
authors.lastname: Deshpande
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Shibahara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053555:Keratin-5 / Q000032:analysis / Q000096:biosynthesis; D053553:Keratin-6 / Q000032:analysis / Q000096:biosynthesis; D008875:Middle Aged; D018300:Papilloma, Intraductal / Q000473:pathology*; D012307:Risk Factors; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D053555:Keratin-5; D053553:Keratin-6; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: CK5/6; atypical papilloma; intraductal papilloma; p63; predictor; subsequent carcinoma