Comparative immunohistochemical analysis of developing kidneys, nephroblastomas and related tumors: Considerations on their histogenesis

Abstract

Immunoperoxidase analysis was performed to evaluate the phenotypic expression of eight renal differentiation antigens in five nephroblastomas, one clear cell sarcoma of the kidney (CCSK), one rhabdoid tumor of the kidney (RTK), and four related tumors. A total of 19 fetal and pediatric kidneys, including two 6th-week mesonephric tissues, were comparatively studied. All the specimens were fixed in formalin and embedded in paraffin. Neural cell adhesion molecule (NCAM), a marker of the nephrogenic zone of the developing kidney, was consistently expressed in the epithelial and blastematous components of nephroblastomas of the common type. The epithelial components also commonly expressed NK1 and Leu 7 (CD57), and the findings may reflect that both were positive in immature proximal tubules directly differentiating from the NCAM-positive immature fetal tubuloglomerular buds. In two cases, the epithelial component was immunoreactive for CD10 and WT1 gene product (WT1-GP). Leu M1, epithelial membrane antigen and CA15-3 were only focally expressed in nephroblastomas. Rhabdomyoblasts in the stroma were positive for WT1-GP. CCSK was featured by the expression of NCAM and CD10. In RTK, focal epithelial differentiation was discerned, with focal positivity of WT1-GP and negativity of NCAM. In congenital mesoblastic nephroma, the stromal spindle cells were strongly immunoreactive for WT1-GP, while WT1-GP was not expressed in solitary multilocular cyst of the kidney. Pancortical nephroblastomatosis was featured by the diffuse subcapsular reappearance of immature metanephric tissue. Nephroblastomas and related conditions thus offer an adequate model for studying human nephrogenesis.

The Expression of WT1 in the Differentiation of Rhabdomyosarcoma from Other Pediatric Small Round Blue Cell Tumors

“…In fact, a similar strong cytoplasmic staining pattern has been previously described in two nephroblastomas within areas of desmin positivity using the same antibody (31). In contrast, previous immunohistochemical reports also described a weak cytoplasmic positivity with WT1 (C-terminus) antibodies in mesotheliomas (23,25), leukemias (20), and SRBCT (24) raising the possibility of an artifact of fixation (24,31,54). Some of the tumors we examined (neuroblastomas, DSRCT, lymphomas, and Wilms' tumors) had a weak cytoplasmic reactivity and nonspecific staining could not be excluded.…”

“…However, an activator or oncogenic behavior may be acquired by missense mutations. WT1 expression has been demonstrated in hema-tological malignancies (17)(18)(19)(20)(21)(22), mesothelial-derived neoplasms (23)(24)(25)(26)(27), breast cancer (28,29), genitourinary tumors (30,31), and small round blue cell tumors (SRBCT; 24,27,[32][33][34]. Recent studies have evaluated the possible role of peripheral blood RNA (18,19), serum antibodies (35), and immunotherapy (36,37) in the diagnosis, monitoring, and treatment of WT1-positive tumors.…”

Sulfated HNK-1 Epitope in Developing and Mature Kidney: A New Marker for Thin Ascending Loop of Henle and Tubular Injury in Acute Tubular Necrosis

“…We and other investigators (Satoh et al 2000) detected the HNK-1 epitope only on the epithelial component, whereas the blastema cells and the fibrous stroma were negative. Metanephric adenoma, another renal tumor that usually behaves in a benign fashion, also expresses the HNK-1 epitope (Muir et al 2001;Skinnider et al 2005).…”

Availability of CD10 as a Histopathological Diagnostic Marker

“…In the liver, canaliculi surrounded by hepatocytes are labeled on their surfaces; however, hepatocytes and bile duct epithelial cells are negative [4]. In the kidney, the epithelial cells of the glomeruli, Bowman's capsule and proximal tubules express CD10 [4,38]. Prostatic glandular epithelial cells are clearly positive, but outer-rim basal cells are consistently negative.…”

“…Therefore, CD10 functions as a cell surface enzyme that acts to reduce cellular responses to peptide hormones by regulating local peptide concentrations [41]. Recently, the investigation of CD10 monoclonal antibodies available to paraffin sections helped to survey CD10 expressions in variable normal and non-hematopoietic neoplastic tissues [1,4,5,22,31,33,38,44]. The availability of these antibodies has contributed to differential diagnoses in the field of surgical pathology (Table 1).…”