Nuclear morphometric analysis of metastasis in Wilms' tumor after multimodal therapy: comparison with primary tumor.
OBJECTIVE
The outlook for children with Wilms' tumor has improved with the use of multimodal therapy, and survival rates now exceed 85%. Yet, 15% of children with tumors with favorable histologic findings continue to recur unpredictably. We previously reported that nuclear morphometry (the distribution of nuclear roundness factor [NRF], lowest values for ellipticity, and age) when combined in a multivariate analysis accurately predicted response to therapy for patients with histologically favorable Wilms' tumors.


METHODS
To investigate further the nuclear shape changes associated with disease recurrence, we analyzed histologic sections taken from primary tumors and postmultimodal therapy metastatic lesions for 7 children who had a recurrence with initially histologically favorable primary tumors.


RESULTS
Mean NRF was significantly lower (P = 0.0001) in the metastatic lesion (35 +/- 5) group when compared with the primary tumor group (50 +/- 5). The percent coefficient of variation for NRF was also significantly lower (P = 0.006) in the metastatic lesion when compared with the primary tumor. Nuclear area was increased (P = 0.02), although the nuclear perimeter was unchanged (P = 0.1).


CONCLUSIONS
(1) Nuclei in metastatic lesions from Wilms' tumors with favorable histologic findings after multimodal therapy are more round and exhibit less variable distribution, suggesting clonal homogeneity within the metastatic lesion. (2) Nuclei in the metastatic lesions have greater area than in the primary tumors yet have an unchanged perimeter, which may be due to internal nuclear expansion secondary to increased cellular deoxyribonucleic acid (DNA) ploidy. Although the results of this study are promising, we are currently extending this hypothesis to a larger group of patients.
Gearhart
J P
JP
Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland.
Willmann
J R
JR
Beckwith
J B
JB
Epstein
J
J
Partin
A W
AW
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002467:Cell Nucleus / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology* / Q000628:therapy; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D009392:Nephrectomy; D011237:Predictive Value of Tests; D011379:Prognosis; D011829:Radiation Dosage; D009396:Wilms Tumor / Q000473:pathology* / Q000556:secondary* / Q000628:therapy