TY - JOUR
T1 - Genetic profile of cumulative mutational damage associated with early pulmonary adenocarcinoma
T2 - Bronchioloalveolar carcinoma vs. stage I invasive adenocarcinoma
AU - Sasatomi, Eizaburo
AU - Johnson, Lawrence R.
AU - Aldeeb, Dalal N.
AU - Lomago, Deren M.
AU - Thompson, James W.
AU - Swalsky, Patricia A.
AU - Luketich, James D.
AU - Fernando, Hiran C.
AU - Finkelstein, Sydney D.
AU - Yousem, Samuel A.
PY - 2004/10
Y1 - 2004/10
N2 - To detect the possible genetic alterations characteristic of bronchioloalveolar carcinoma (BAC) and to study molecular genetic factors responsible for determining the biologic aggressiveness of pulmonary adenocarcinoma, comparative analysis of loss of heterozygosity (LOH) on 9 chromosomal regions was performed in 14 BACs and in 20 stage I adenocarcinomas (AD). The most frequently affected chromosome regions in BAC were 8q and 17p. In stage I AD, more than 60% of the cases showed LOH of 1p, 3p, 5q, 7q, 17p, and 18q loci, and LOH of 1p, 3p, 7q, and 18q was observed with greater frequency than in BAC (P < 0.05). Fractional allele loss (FAL) was significantly greater in stage I AD than in BAC (P < 0.001). In cases with microdissection of multiple sites, intratumoral heterogeneity of LOH status was observed in 73% of BAC and 94% of stage I AD, and homogeneous distribution of LOH of 9p was unique to BAC. The high FAL value was associated with a poor prognosis of BAC, but this trend did not reach statistical significance (P = 0.098). In stage I AD, no correlation was found between LOH of particular chromosomal region or FAL and clinical outcome. LOH of 1p, 3p, 7q, and 18q was associated with invasive properties of pulmonary AD and may be useful in identifying invasive adenocarcinoma when conventional histomorphological tools are not helpful.
AB - To detect the possible genetic alterations characteristic of bronchioloalveolar carcinoma (BAC) and to study molecular genetic factors responsible for determining the biologic aggressiveness of pulmonary adenocarcinoma, comparative analysis of loss of heterozygosity (LOH) on 9 chromosomal regions was performed in 14 BACs and in 20 stage I adenocarcinomas (AD). The most frequently affected chromosome regions in BAC were 8q and 17p. In stage I AD, more than 60% of the cases showed LOH of 1p, 3p, 5q, 7q, 17p, and 18q loci, and LOH of 1p, 3p, 7q, and 18q was observed with greater frequency than in BAC (P < 0.05). Fractional allele loss (FAL) was significantly greater in stage I AD than in BAC (P < 0.001). In cases with microdissection of multiple sites, intratumoral heterogeneity of LOH status was observed in 73% of BAC and 94% of stage I AD, and homogeneous distribution of LOH of 9p was unique to BAC. The high FAL value was associated with a poor prognosis of BAC, but this trend did not reach statistical significance (P = 0.098). In stage I AD, no correlation was found between LOH of particular chromosomal region or FAL and clinical outcome. LOH of 1p, 3p, 7q, and 18q was associated with invasive properties of pulmonary AD and may be useful in identifying invasive adenocarcinoma when conventional histomorphological tools are not helpful.
KW - Adenocarcinoma
KW - Bronchioloalveolar carcinoma
KW - Loss of heterozygosity
KW - Lung
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U2 - 10.1097/01.pas.0000138001.69521.0e
DO - 10.1097/01.pas.0000138001.69521.0e
M3 - Article
C2 - 15371943
AN - SCOPUS:5044241540
SN - 0147-5185
VL - 28
SP - 1280
EP - 1288
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 10
ER -