Am. J. Respir. Cell Mol. Biol.,
Volume 23, Number 5, November, 2000 636-645
Phenotypically Different Cells with Heterogeneous Nuclear
Ribonucleoprotein A2/B1 Overexpression Show Similar Genetic Alterations
Yan-Gao
Man,
Alfredo
Martinez,
Ingalill M.
Avis,
Sung H.
Hong,
Frank
Cuttitta,
David J.
Venzon,
and
James L.
Mulshine
Intervention Section, Department of Cell and Cancer Biology; and Biostatistics and Data Management Section, Medicine Branch,
Division of Clinical Science, National Cancer Institute, Bethesda, Maryland
Immunocytochemical studies have revealed that overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/
B1 in exfoliated epithelial cells is a potentially useful marker of early lung cancer. This study analyzed the correlation of
hnRNP A2/B1 expression with molecular alterations in phenotypically different epithelial cells of paraffin-embedded pulmonary tissues. Sections from 20 human subjects were analyzed immunohistochemically for expression of hnRNP A2/B1.
Normal-appearing, hyperplastic, and malignant epithelial cells
with and without hnRNP A2/B1 expression (n = 78) were microdissected and assessed for microsatellite alterations (MA)
and loss of heterozygosity (LOH) (n = 14 markers) as well as
for clonality. Results showed that (1) hnRNP A2/B1 immunoreactive cells contained a significantly higher frequency of
MA and LOH than did comparable cells that lacked detectable
hnRNP A2/B1; (2) over 80% of MA and LOH seen in hnRNP
A2/B1 immunoreactive normal-appearing and hyperplastic
cells persisted in malignant cells; (3) preliminary analysis of
methylation status of the androgen receptor gene in non-neoplastic cells was suggestive of hnRNP A2/B1-expressing cells
being of clonal origin; and (4) cells with cytoplasmic hnRNP
A2/B1 immunoreactivity had a 3-fold higher frequency of MA
and LOH than did cells with nuclear hnRNP A2/B1 immunoreactivity. These findings suggest that phenotypically different
respiratory epithelial cells with hnRNP A2/B1 overexpression
might be clonally derived, and that the subcellular localization
of hnRNP A2/B1 might be an important factor associated with
tumor progression.
