Vitamin D receptor expression in normal, premalignant, and malignant human lung tissue.
BACKGROUND
There is a strong interest in identifying chemopreventive agents that might help decrease the burden of lung cancer. The active metabolite of vitamin D, 1,25-dihydroxycholecalciferol (calcitriol), has been shown to have antiproliferative effects in several tumor types, mediated by the vitamin D receptor (VDR). This is the first comprehensive survey of VDR expression in a series of human lung tissues, including normal and premalignant central airway biopsies and lung tumors.


METHODS
Immunohistochemical expression of nuclear and cytoplasmic VDR was examined in 180 premalignant or malignant bronchial biopsies from bronchoscopy of 78 high-risk individuals at the Roswell Park Cancer Institute and also in 63 tumor samples from 35 lung cancer patients from the University of Chicago Hospitals. Associations between clinicopathologic data and VDR expression were examined.


RESULTS
VDR expression was present in many samples. In biopsies, VDR was commonly detected throughout the full epithelial layer. Most histologically normal (60%, 53 of 88) and metaplastic (61%, 39 of 64) samples had moderate to high nuclear intensity; dysplastic samples mostly had low nuclear intensity (10 of 18, 55%). In tumor samples, 62% (38 of 61) were lacking cytoplasmic VDR, with nuclear expression present in 79%(49 of 62). Analysis of all samples revealed a positive linear trend between proportion of samples with greater nuclear than cytoplasmic intensity and increasing histologic grade (P < 0.01).


CONCLUSIONS
VDR expression spanned the lung carcinogenesis spectrum. Nuclear expression was similar across various histologies, whereas cytoplasmic expression decreased with increasing histologic grade. These results indicate that there is potential for the use of calcitriol as a chemopreventive agent against the development of lung cancer.
Menezes
Ravi J
RJ
Department of Cancer Prevention and Control Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Cheney
Richard T
RT
Husain
Aliya
A
Tretiakova
Maria
M
Loewen
Gregory
G
Johnson
Candace S
CS
Jayaprakash
Vijay
V
Moysich
Kirsten B
KB
Salgia
Ravi
R
Reid
Mary E
ME
D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism*; D018709:Statistics, Nonparametric
D014408:Biomarkers, Tumor; D018167:Receptors, Calcitriol