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. 2018 Jan 22;13(1):9.
doi: 10.1186/s13000-018-0686-z.

Tissue expression of retinoic acid receptor alpha and CRABP2 in metastatic nephroblastomas

Ana Paula Percicote  1 , Gabriel Lazaretti Mardegan  2 , Elizabeth Schneider Gugelmim  3 , Sergio Ossamu Ioshii  4 , Ana Paula Kuczynski  5 , Seigo Nagashima  6 , Lúcia de Noronha  4
Affiliations

Tissue expression of retinoic acid receptor alpha and CRABP2 in metastatic nephroblastomas

Ana Paula Percicote et al. Diagn Pathol. .

Abstract

Background: Nephroblastoma or Wilms tumor is the most frequent kidney cancer in children and accounts for 98% of kidney tumors in this age group. Despite favorable prognosis, a subgroup of these patients progresses to recurrence and death. The retinoic acid (RA) pathway plays a role in the chemoprevention and treatment of tumors due to its effects on cell differentiation and its antiproliferative, anti-oxidant, and pro-apoptotic activities. Reports describe abnormal cellular retinoic acid-binding protein 2 (CRABP2) expression in neoplasms and its correlation with prognostic factors and clinical and pathological characteristics. The aim of this study was to evaluate the immunohistochemical expression of retinoic acid receptor alpha (RARA) and CRABP2 in paraffin-embedded samples of nephroblastomas via semiquantitative and quantitative analyses and to correlate this expression with prognostic factors.

Methods: Seventy-seven cases of nephroblastomas were selected from pediatric oncology services. The respective medical records and surgical specimens were reviewed. Three representative tumor samples and one non-tumor renal tissue sample were selected for the preparation of tissue microarrays (TMA). The Allred scoring system was used for semiquantitative immunohistochemical analyses, whereas a morphometric analysis of the stained area was employed for quantitative evaluation. The nonparametric Mann-Whitney test was used for comparisons between two groups, while the nonparametric Kruskal-Wallis test was used to compare three or more groups.

Results: Immunopositivity for RARA and CRABP2 was observed in both the nucleus and cytoplasm. All histological components of the nephroblastoma (blastema, epithelium, and stroma) were positive for both markers. RARA, based on semiquantitative analyses, and CRABP2, bases on quantitative analyses, exhibited increased immunohistochemical expression in patients with metastasis, with p values of 0.0247 and 0.0128, respectively. These findings were similar to the results of the quantitative analysis of RARA expression, showing greater immunopositivity in tumor samples of patients subjected to pre-surgical chemotherapy. No significant correlation was found with the other variables studied, such as disease stage, anaplasia, risk group, histological type, nodal involvement, and clinical evolution.

Conclusions: Semiquantitative and quantitative analyses of the markers RARA and CRABP2 indicate their potential as biomarkers for tumor progression and their participation in nephroblastoma tumorigenesis.

Keywords: CRABP2; Nephroblastoma; Retinoic acid.

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The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Immunohistochemical expression of RARA and CRABP2 in nephroblastoma samples. RA immunoexpression: a, blastema; b, epithelium; c, stroma; CRABP2 immunoexpression: d, blastema; e, epithelium; f, stroma (40×)
Fig. 2
Fig. 2
a Quantitative analysis of RARA immunoexpression as a function of the presence of metastasis. The box-plot represents the results of the quantitative analysis of RARA immunoexpression according to the presence of metastasis, showing RARA immunoexpression in nephroblastomas with and without metastasis. Increased immunopositivity was observed in patients with metastasis (p = 0.0247). b and c Immunohistochemical expression of RARA in nephroblastomas without (b) and with metastasis (c) (63×). d Quantitative analysis of RARA immunoexpression as a function of the initial treatment. The box-plot represents the results of the quantitative analysis of RARA immunoexpression according to the type of initial treatment, showing RARA immunoexpression in nephroblastoma samples from patients subjected to pre-surgical chemotherapy and patients subjected to surgery as initial treatment (p = 0.0330). e and f Immunohistochemical expression of RARA in nephroblastoma samples from patients subjected to surgery (e) and pre-surgical chemotherapy (f) (63×). g Semiquantitative analysis of CRABP2 immunoexpression as a function of the presence of metastasis. The box-plot represents the results of the quantitative analysis of CRABP2 immunoexpression according to the presence of metastasis, showing CRABP2 immunoexpression in nephroblastomas with and without metastasis. Increased immunopositivity was observed in patients with metastasis (p = 0.0128). h and i Immunohistochemical expression of CRABP2 in nephroblastoma without (h) and with metastasis (i) (63×)
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