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3p21, 5q21, 9p21 and 17p13 allelic deletions
accumulate in the dysplastic spectrum of laryngeal carcinogenesis
and precede malignant transformation
J. Sanz-Ortega, C. Valor, M.C. Saez, L. Ortega, E. Sierra,
J. Poch, S. Hernández and J. Sanz-Esponera
Department of Pathology, San Carlos Clinic Hospital, Madrid,Spain
Offprint requests to: Dr. J. Sanz-Ortega, Departamento de Anatomía
Patológica, Hospital Clínico San Carlos, Martín
Lagos s/n, 28040 Madrid, Spain
Summary. A tissue field of somatic genetic alterations
precede the histopathological phenotypic changes of carcinoma.
Loss of Heterozygosity (LOH) at the sites of known or putative
tumor suppressor genes is a common genetic abnormality detected
in precancerous conditions. These genomic changes could be of
potential use in the diagnosis and prognosis of pre-malignant
laryngeal lesions. Recently the concept of laryngeal intraepithelial
neoplasia (LIN) was introduced. To evaluate patients with an
increased risk of developing invasive laryngeal carcinoma via
a dysplasia-carcinoma progression we investigated 102 microdissected
cell populations. Cell populations were procured from 15 laryngectomy
specimens with different peritumoral histological changes adjacent
to the squamous cell carcinoma cells and 15 laryngeal endoscopic
biopsies with no evidence of malignant transformation in a 6-10-year
follow-up period. Histological diagnoses were subdivided into
keratosis without dysplasia (KWD), with mild dysplasia (LIN 1),
with moderate dysplasia (LIN 2), and with severe dysplasia or
carcinoma in situ (LIN 3). Microsatellite analysis was performed
with the aim of studying LOH of 5q21 (APC), 9p21 (p16), 3p21
and 17p13 (p53) chromosomal regions. Frequent allelic losses
were found in carcinoma cells at p53 (54%), p16 (66%), 3p21(87%)
and 5q21(58%). Identical LOH patterns were determined in 100%
of the LIN3 peritumoral cells, 60% of LIN2, 50% of LIN 1 and
25% of KWD. In contrast, histologically normal mucosae, KWD and
LIN1 lesions without malignant progression showed no allelic
loss. These results show that dysplasia correlates with LOH at
3p21, 5q21, 9p21 and 17p13 in early laryngeal carcinogenesis.
These genomic changes in pre-malignant laryngeal lesions could
be of potential use as markers for cancer risk assessment. Histol.
Histopathol. 18, 1053-1057 (2003)
Key words: Carcinoma, Microdissection, Larynx, Loss
of heterozygosity
DOI: 10.14670/HH-18.1053
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