title: Keratin 15, transcobalamin I and homeobox gene Hox-B13 expression in breast phyllodes tumors: novel markers in biological classification.
abstract: Breast phyllodes tumors are rare neoplasms which present challenges for histological classification. Microscopic features are not always predictive of clinical behavior, and scarce data exist on the prognostic role of biological markers. Our study evaluated a series of 145 phyllodes tumors diagnosed at the Department of Pathology, Singapore General Hospital between 2006 and 2009, incorporating 91 (62.8%) benign, 40 (27.6%) borderline, and 14 (9.7%) malignant phyllodes tumors. Antibodies to keratin 15 (KRT15), transcobalamin I (TCN1), and homeobox gene Hox-B13 (HOXB13) were applied to sections cut from tissue microarray blocks. KRT15 and TCN1 positivity was defined when there was reactivity of 1% or more stromal cells, while HOXB13 positivity was defined using a H-score of 100 and above. Positive immunohistochemical expression for KRT15, TCN1, and HOXB13 was seen in 21 (14.5%), 96 (66.2%), and 66 (45.5%) of tumors, respectively. Stromal expression of KRT15, TCN1, and HOXB13 was significantly correlated with tumor grade (P < 0.001, P < 0.001, P = 0.012), stromal hypercellularity (P = 0.005, P < 0.001, P = 0.023), mitotic activity (P < 0.001), and microscopic borders (P = 0.006, P < 0.001, P = 0.011). Co-expression of TCN1 and HOXB13 was seen in 21 of 91 (23.1%) benign, 18 of 40 (45.0%) borderline, and 11 of 14 (78.6%) malignant tumors, suggesting that the dual-marker panels of TCN1 and HOXB13 might be helpful in classifying borderline and malignant tumors. Although expression of TCN1 alone was present in all malignant and 34 of 40 (85.0%) borderline tumors, a combined panel with HOXB13 excluded some benign cases and was a better discriminant for a significant proportion of borderline and malignant tumors.
authors.affiliation: Department of Pathology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.
authors.forename: Luke Yong-Zheng
authors.initials: LY
authors.lastname: Chong
authors.forename: Poh Yian
authors.initials: PY
authors.lastname: Cheok
authors.forename: Wai-Jin
authors.initials: WJ
authors.lastname: Tan
authors.forename: Aye Aye
authors.initials: AA
authors.lastname: Thike
authors.forename: George
authors.initials: G
authors.lastname: Allen
authors.forename: Mei Kim
authors.initials: MK
authors.lastname: Ang
authors.forename: Aik Seng
authors.initials: AS
authors.lastname: Ooi
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
authors.forename: Puay Hoon
authors.initials: PH
authors.lastname: Tan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053569:Keratin-15 / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged; D003557:Phyllodes Tumor / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis; D014155:Transcobalamins / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C484414:HOXB13 protein, human; D018398:Homeodomain Proteins; C116015:KRT15 protein, human; D053569:Keratin-15; D014155:Transcobalamins