Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer.
The aim of this study was to investigate the expression of the protein tyrosine phosphatases (PTP) PRL-1, PRL-2, and PRL-3 in human breast cancer and to evaluate its clinical and prognostic significance. PRL-PTP mRNA expression was examined in malignant (n = 7) and nonmalignant (n = 7) cryoconserved breast tissue samples as well as in eight breast cancer cell lines by RT-PCR. Furthermore, protein expression of PRL-3 was analysed semiquantitatively by immunohistochemistry in ductal breast carcinoma in situ (n = 135) and invasive breast cancer (n = 147) by use of tissue microarray technology (TMA). In 24 lymph node-positive patients we selected the corresponding lymph node metastases for analysis of PRL-3 expression, and a validation set (n = 99) of invasive breast cancer samples was examined. Staining results were correlated with clinicopathological parameters and long-term follow-up. PRL-3 mRNA expression was significantly higher in malignant compared to benign breast tissue. For PRL-1 and PRL-2 expression no significant differences were observed. Staining of TMAs showed PRL-3 expression in 85.9% ductal carcinoma in situ and 75.5% invasive breast carcinomas. Analysis of survival parameters revealed a shorter disease-free survival (DFS) in patients with PRL-3-positive carcinomas, and in particular a significantly shorter DFS in nodal-positive patients with PRL-3 overexpressing tumours as compared to PRL-3-negative breast carcinomas (66+/-7 months (95% CI, 52-80) vs 97+/-9 months (95% CI, 79-115); P = 0.032). Moreover, we found a more frequent expression of PRL-3 in lymph node metastases as compared to the primary tumours (91.7 vs 66.7%; P = 0.033). Our results suggest that PRL-3 might serve as a novel prognostic factor in breast cancer, which may help to predict an adverse disease outcome.
Radke
I
I
Department of Obstetrics and Gynaecology, University of Münster, Albert-Schweitzer-Str. 33, D-48149 Münster, Germany. Isabel.Radke@ukmuenster.de
Götte
M
M
Kersting
C
C
Mattsson
B
B
Kiesel
L
L
Wülfing
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C490198:PTP4A1 protein, human; C487561:PTP4A2 protein, human; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases