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 cystadenomas and 41 low malignant potential (LMP) tumours and compared the results with those for p53 protein expression, clinicopathological factors and survival. A combination of the reverse transcription polymerase chain reaction (RT-PCR) and Southern blot hybridization (SBH) for DCC mRNA levels was also carried out on 26 malignant, five LMP, eight benign and seven normal ovarian samples. Significantly decreased levels of overall DCC values in carcinomas compared with benign and LMP lesions were revealed by both immunohistochemical and RT-PCR/SBH assays. Similar findings were also noted when subdivision 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 immunopositivity demonstrated significant stepwise increase from benign through to malignant 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.
Saegusa
M
M
Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Machida
D
D
Okayasu
I
I
D001483:Base Sequence; D015139:Blotting, Southern; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D000075389:DCC Receptor; D017931:DNA Primers; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016163:Genes, DCC; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; D017931:DNA Primers; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins