Background: Although frequent loss of the tumor suppressor gene deleted in colon carcinoma (DCC) has been demonstrated in endometrial carcinoma, an alteration 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 with 90 hyperplasias (23 simple, 30 complex, and 37 atypical) and 143 normal endometria (28 atrophic, 44 proliferative, and 71 secretory), were immunohistochemically investigated for expression of DCC as well as for estrogen and progesterone receptors (ER and PR). Analysis for DCC mRNA levels was also 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 related 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 evidence of malignancy and lymph node metastasis, and this was in keeping with the results of mRNA analysis. The transcripts derived from alternative splicing 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 normal menstrual cycle without any relation to immunoreactivity for ovarian hormone receptors. Moreover, loss or reduction of expression may be a significant event in the progression of endometrial carcinoma through metastatic features.