M. Kiechle et al., Comparative genomic hybridization detects genetic imbalances in primary ovarian carcinomas as correlated with grade of differentiation, CANCER, 91(3), 2001, pp. 534-540
BACKGROUND. In the current study the authors attempted to evaluate genetic
alterations in a large set of primary ovarian carcinomas and to compare the
genetic findings with clinical parameters such as grade of tumor different
iation. This strategy was applied to identify chromosomal regions containin
g genes associated with tumor progression.
METHODS. Genetic imbalances were assessed in 106 primary ovarian carcinomas
using comparative genomic hybridization (CGII). CGH was applied because it
is a powerful tool with which to screen the entire genome of a tumor for g
enetic changes by highlighting regions of altered DNA sequence copy numbers
(deletions and amplifications). Multivariate statistical standard procedur
es were used to determine an association between tumor grading and genetic
alterations.
RESULTS. One hundred three carcinomas showed aberrant CGH profiles. The mos
t frequent alterations were amplifications of 8q, 1q, 20q, 3q, and 19p, whi
ch occurred in 69-53% of tumors, and underrepresentations of 13q, 4q, and 1
8q, which occurred in 54-50% of tumors. Undifferentiated ovarian carcinomas
(World Health Organization Grade 3) were found to be correlated significan
tly with underrepresentation of 11p and 13q as well as with overrepresentat
ion of 8q and 7p (P = 0.001, 0.001, 0.01, and 0.027, respectively). However
, 12p underrepresentation and 18p overrepresentation were significantly mor
e frequent in well and moderately differentiated tumors (P = 0.01 and 0.004
, respectively), To facilitate the interpretation and clinical application
of the results of the current study, the significant aberrations were trans
lated into a score system. This score system can be used easily for the pre
diction of an undifferentiated phenotype with a specificity and sensitivity
of 79% and 86%, respectively.
CONCLUSIONS. The current study data show that primary ovarian carcinomas ar
e based on consistent genetic alterations that most likely are important fo
r the development of this tumor entity. The correlation between certain abe
rrations and undifferentiated carcinomas may help to discriminate between p
rimary and secondary genetic events and may indicate the location of those
genes Involved in cellular functions associated with tumor progression and
the development of anaplastic and aggressive phenotypes. (C) 2001 American
Cancer Society.