Loss of DCC gene expression during ovarian tumorigenesis: relation to tumour differentiation and progression

To clarify the possible role of DCC gene alteration in ovarian neoplasias, we immunohistochemically investigated 124 carcinomas, as well as 55 cystade nomas and 41 low malignant potential (LMP) tumours and compared the results with those for p53 protein expression, clinicopathological factors and sur vival. A combination of the reverse transcription polymerase chain reaction (RT-PCR) and Southern blot hybridization (SBH) for DCC mRNA levers was als o carried out on 26 malignant, five LMP, eight benign and seven normal ovar ian samples. Significantly decreased levels of overall DCC Values in carcin omas compared with benign and LMP lesions were revealed by both immunohisto chemical and RT-PCR/SBH assays. Similar findings were also noted when subdi vision was into serous and mucinous categories. In carcinomas, reduction or loss of DCC expression was significantly related to the serous phenotype ( serous vs non-serous, P < 0.0001), a high histological grade (grade 1 vs 2 or 3, P< 0.02) and a more advanced stage (FIGO stage I vs II/III/IV, P = 0. 0083), while no association was noted with survival. Although p53 immunopos itivity demonstrated significant stepwise increase from benign through to m alignant lesions, there was no clear association with DCC score values. The results indicated that impaired DCC expression may play an important role in ovarian tumorigenesis. In ovarian carcinomas, the altered expression is closely linked with tumour differentiation and progression. (C) 2000 Cancer Research Campaign.