Loss of expression of the gene deleted in colon carcinoma (DCC) is closelyrelated to histologic differentiation and lymph node metastasis in endometrial carcinoma
M. Saegusa et al., Loss of expression of the gene deleted in colon carcinoma (DCC) is closelyrelated to histologic differentiation and lymph node metastasis in endometrial carcinoma, CANCER, 85(2), 1999, pp. 453-464
BACKGROUND. Although frequent loss of the tumor suppressor gene deleted in
colon carcinoma (DCC) has been demonstrated in endometrial carcinoma, an al
teration of the expression during normal menstrual cycle and tumorigenesis
from hyperplastic lesions is still unclear.
METHODS. A total of 151 endometrial carcinomas (endometrioid type), along w
ith 90 hyperplasias (23 simple, 30 complex, and 37 atypical) and 143 normal
endometria (28 atrophic, 44 proliferative, and 71 secretory), were immunoh
istochemically investigated far expression of DCC as well as for estrogen a
nd progesterone receptors (ER and PR). Analysis for DCC mRNA levels was als
o performed on 37 endometrial carcinomas and 14 normal endometria.
RESULTS. DCC expression was observed in endometrial glandular cells in both
proliferative and secretory stages; the immunoreactivity scores were not r
elated to values for either ER or PR. The Values for DCC were significantly
higher in hyperplasia than in normal endometria, and then decreased in the
sequence leading to Grade 3 carcinoma. In endometrial carcinoma, reduction
or loss of DCC expression was significantly related to the histologic evid
ence of malignancy and lymph node metastasis, and this was in keeping with
the results of mRNA analysis. The transcripts derived from alternative spli
cing in the extracellular domain were not observed in any tumor samples.
CONCLUSIONS. The findings of this study indicate that DCC expression may be
linked to the maintenance of differentiated glandular cells during the nor
mal menstrual cycle without any relation to immunoreactivity for ovarian ho
rmone receptors. Moreover, loss or reduction of expression may be a signifi
cant event in the progression of endometrial carcinoma through metastatic f
eatures. (C) 1999 American Cancer Society.