High levels of cellular retinol binding protein-1 expression in leiomyosarcoma: possible implications for diagnostic evaluation

Abstract

Retinoid bioavailability is regulated by the activity of specific cytoplasmic receptors. High levels of cellular retinol binding protein-1 (CRBP-1) have been documented during experimental arterial and wound-healing processes, but data concerning neoplastic smooth muscle tissues are scarce and/or controversial. This study reports that the expression of CRBP-1 is markedly higher in uterine and gastrointestinal leiomyosarcomas than in leiomyomas and normal myometrium; CRBP-1 was practically absent in normal gastrointestinal smooth muscle tissue. CRBP-1 positivity was particularly elevated in the epithelioid variant of leiomyosarcoma; it was associated with increased proliferative and apoptotic rates and inversely related to smooth muscle differentiation evaluated by alpha- and gamma-smooth muscle actin and desmin expression. Western blotting and reverse-transcription polymerase chain reaction confirmed the observations concerning CRBP-1 and actin isoform expression and revealed higher NF-kappa-Bp65 and RAR alpha and lower Bax protein levels in leiomyosarcoma than in the other conditions. These findings document that a high CRBP-1 expression is associated with smooth muscle malignancy and suggest that CRBP-1 expression represents a new useful marker for the classification of unusual variants of smooth muscle tumors.

Aberrant cellular retinol binding protein 1 (CRBP1) gene expression and promoter methylation in prostate cancer

“…Such a finding has not been described in other epithelial neoplasms, but was reported in leiomyosarcomas, particularly in the epithelioid variant. 21 A significant association was then established between CRBP1 overexpression and tumour differentiation, 21 but such an association was not found among our patients with prostate cancer, taking the Gleason score as a measure of neoplastic differentiation (data not shown). At first glance, CRBP1 overexpression may seem a disadvantageous acquisition by prostate cancer cells, but this change could represent a side effect of the altered expression of other genes in a subset of prostate tumours, rather than a primary event in prostate carcinogenesis.…”

The Ki67+ proliferation index correlates with increased cellular retinol‐binding protein‐1 and the coordinated loss of plakophilin‐1 and desmoplakin during progression of cervical squamous lesions

“…Significant elevation of CRBP‐1 has been observed in tumour samples of endometrial adenocarcinoma 11 and in a subset of hepatocellular carcinoma 8 . CRBP‐1 expression has been reported to be markedly higher in uterine and gastrointestinal leiomyosarcomas than in leiomyomas and normal myometrium, with particularly elevated positivity in the epithelioid variant of leiomyosarcoma 14 . The mechanisms which regulate CRBP‐1 expression are still incompletely understood.…”

“…On the other hand, ROL‐deficient tissues such as fibrotic liver may show increased levels of CRBP‐1 expression 8,9 . Abnormalities of CRBP‐1 expression have been demonstrated in a variety of malignancies 6–8,10–15 . However, there is limited information in the literature pertaining to a potential modulation of retinoid‐binding proteins in cervical carcinogenesis 16–18 .…”

“…8,9 Abnormalities of CRBP-1 expression have been demonstrated in a variety of malignancies. [6][7][8][10][11][12][13][14][15] However, there is limited information in the literature pertaining to a potential modulation of retinoid-binding proteins in cervical carcinogenesis. [16][17][18] The present imaging study was undertaken to analyse the expression of CRBP-1 during the progression of cervical squamous intraepithelial lesions (SIL) to squamous cell carcinoma (SCC) in correlation with the Ki67 proliferation index (PI).…”

Mapping, tissue distribution and polymorphism of porcine genes encoding retinol binding proteins (RBP1 and RBP4)

“…More research is needed on this issue. On the other hand, a relationship between RBP1 and RBP4 expression and obesity, diabetes and cancer of smooth muscle has already been reported (Orlandi et al, 2002;Yang et al, 2005). RBP4 has been indicated as a candidate gene for pig farrowing numbers (Rothschild et al, 2000).…”