Nephroblastoma: multidrug-resistance P-glycoprotein expression in tumor cells and intratumoral capillary endothelial cells.
The development of chemoresistance in a variety of cancers seems related to overexpression of the P-glycoprotein (P-gp) drug pump. Nephroblastoma, the most common malignant renal tumor of childhood, usually is responsive to treatment, and prognosis is favorable in most cases. However, the disease in a subset of patients is refractory to treatment, and the disease follows an aggressive course. To study P-gp expression in this tumor and its correlation with outcome, tumor samples from 93 patients were examined by immunohistochemical analysis. P-gp expression was determined separately in both tumor cells and intratumoral capillary endothelium. The likelihood ratio test, the Kaplan-Meier method, and the log-rank test were used to evaluate its association with clinical course, grade, stage, and administration of preoperative chemotherapy. The results for the majority of nephroblastomas were variably positive; in 43 (46%) of them, newly formed capillary endothelial cells also stained positive. While no association of P-gp expression in tumor cells with clinical course, stage, and grade could be demonstrated, positivity in endothelial cells correlated significantly with unfavorable outcome, suggesting that chemoresistance depended on an active blood-tumor barrier. Previous chemotherapy induced P-gp overexpression in tumor cells.
Camassei
Francesca Diomedi
FD
Department of Pathology, Bambino Gesù Children's Hospital-Research Institute, Rome, Italy.
Arancia
Giuseppe
G
Cianfriglia
Maurizio
M
Bosman
Cesare
C
Francalanci
Paola
P
Ravà
Lucilla
L
Jenkner
Alessandro
A
Donfrancesco
Alberto
A
Boldrini
Renata
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002196:Capillaries; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003609:Dactinomycin / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000628:therapy; D008297:Male; D009367:Neoplasm Staging; D011182:Postoperative Care; D011300:Preoperative Care; D011878:Radiotherapy; D012074:Remission Induction; D012189:Retrospective Studies; D014750:Vincristine / Q000627:therapeutic use; D009396:Wilms Tumor / Q000737:chemistry* / Q000473:pathology* / Q000628:therapy
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003609:Dactinomycin; D014750:Vincristine