Anaplastic Wilms' tumor: clinical and pathologic studies.

Abstract

A review of almost 1,200 children participating in the first and second National Wilms' Tumor Study (NWTS-1 and -2) has demonstrated a number of significant differences in the clinical presentation and response to therapy of anaplastic and nonanaplastic Wilms' tumor. Compared to their counterparts, children with anaplastic Wilms' tumor were generally one to two years older at diagnosis, more were non-white, and more had lymph node metastases at diagnosis. Consistent with previous studies, children with anaplastic Wilms' tumor survived for a significantly shorter time than those with non-anaplastic Wilms' tumor. A hopeful outlook, however, was suggested by the NWTS-2 experience since the more aggressive chemotherapies used in this study appear to have substantially improved the survival of patients with diffusely anaplastic tumors. Also, the survival of NWTS-2 patients with anaplastic Wilms' tumor was determined in part by clinicopathologic stage. It may be possible therefore to refine therapy according to stage so as to provide children with localized disease a chance for cure with fewer untoward treatment-related sequelae.

Calcineurin A–Binding Protein, a Novel Modulator of the Calcineurin-Nuclear Factor of Activated T-Cell Signaling Pathway, Is Overexpressed in Wilms' Tumors and Promotes Cell Migration

“…This is especially relevant in the context of WT recurrence observed in 15% of cases. These tumors are generally resistant to treatment regardless of histologic features and acquire the capacity to migrate and invade surrounding tissues (5,6). This link between WT recurrence and increased cell dissemination (6) is entirely compatible with the cellular functions we identified for CnABP.…”

“…However, 15% to 20% of WT patients experience relapse associated with resistance to treatments and poor prognosis (3,4). An increased probability of relapse and mortality correlates with anaplasia and metastasis (5,6) as well as increased chromosomal anomalies (7,8). At the molecular level, relapse has been linked to consistent deregulation of a limited number of genes, including components of the calcineurin signaling pathway (9).…”

Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia

“…While the disease progression of these three patients was concordant with the concept that anaplastic tumors progresses from FH tumors, the 97 clones we identified were capable of capturing the molecular differences between these two subtypes of Wilms tumors. Anaplastic nuclear changes are associated with increased resistance to adjuvant therapy (Beckwith and Palmer, 1978;Bonadio et al, 1985). As expected, we recognized several genes among the 97 clones (76 genes) that may contribute either to nuclear morphology or therapeutic resistance (Table 2).…”

“…Although it is relatively rare (3.2-7.3% of all Wilms tumors), this subset of tumors is clinically important since anaplastic tumors are typically resistant to therapy and have poor prognosis (Beckwith and Palmer, 1978;Bonadio et al, 1985). The molecular basis for the anaplastic phenotype is unknown; however, unlike Wilms tumors with favorable histology (FH), most anaplastic tumors contain somatic p53 mutations (Bardeesy et al, 1994(Bardeesy et al, , 1995.…”

A Gene Expression Signature for Relapse of Primary Wilms Tumors

“…Therefore, it is important to identify patients at the time of diagnosis who might benefit from intensified initial treatment to prevent future relapse as well as those who might be cured with limited treatment and reduced toxicity. Anaplasia (unfavorable histology) and metastasis (stage) are each associated with higher relapse and mortality rates in Wilms tumor patients (4,5). Nevertheless, not all anaplastic tumors relapse and some primary tumors with favorable histology relapse unexpectedly (6,7).…”