Prognostic value of thymidine phosphorylase expression in breast carcinoma.
Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), is an enzyme that catalyzes the reversible dephosphorylation of thymidine, deoxyuridine and their analogs. TP has also angiogenic properties, although the precise mechanism by which it promotes angiogenesis is not known. We examined TP expression using immunohistochemistry (654-1 Mab) in 182 invasive breast carcinomas (67 N0 and 115 N1/2; median follow-up 78 months [range, 3-177]; 51 patients treated with adjuvant systemic cyclophosphamide, methotrexate and 5-fluorouracil [CMF] chemotherapy and 82 with tamoxifen). High TP expression was found in 142 cases (78%) and correlated with lower histologic grade and low p53 expression. No correlation was found between TP expression and vascular density. TP-positive tumors had a significant increase in both disease-free survival (DFS; p = 0.0025) and overall survival (OS; p = 0.0070) in the total cohort of patients and in the subgroups of node-positive patients and patients treated with CMF adjuvant therapy; no significant difference in either DFS or OS was observed in patients without CMF treatment. Our findings suggest that TP has little effect on tumor angiogenesis of breast carcinoma, whereas it could represent an interesting marker that could predict response to CMF chemotherapy.
Yang
Qifeng
Q
Second Department of Pathology, Wakayama Medical University School of Medicine, Wakayama City, Japan. yang-qf@mail.wakayama-med.ac.jp
Barbareschi
Mattia
M
Mori
Ichiro
I
Mauri
Francesco
F
Muscarà
Maurizio
M
Nakamura
Misa
M
Nakamura
Yasushi
Y
Yoshimura
Goro
G
Sakurai
Takeo
T
Caffo
Orazio
O
Galligioni
Enzo
E
Dalla Palma
Paolo
P
Kakudo
Kennichi
K
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D002277:Carcinoma / Q000098:blood supply / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply / Q000188:drug therapy / Q000201:enzymology / Q000401:mortality / Q000601:surgery; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics; D005500:Follow-Up Studies; D006801:Humans; D015993:Life Tables; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis*; D009389:Neovascularization, Pathologic / Q000201:enzymology; D011237:Predictive Value of Tests; D011379:Prognosis; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use; D013939:Thymidine Phosphorylase / Q000032:analysis*
D018931:Antineoplastic Agents, Hormonal; D009363:Neoplasm Proteins; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D003520:Cyclophosphamide; D013939:Thymidine Phosphorylase; D005472:Fluorouracil; D008727:Methotrexate