Serous tubal intraepithelial carcinoma upregulates markers associated with high-grade serous carcinomas including Rsf-1 (HBXAP), cyclin E and fatty acid synthase.
Serous tubal intraepithelial carcinoma (STIC) has been proposed as a precursor for many pelvic high-grade serous carcinomas. Our previous analysis of the ovarian cancer genome identified several genes with oncogenic potential that are amplified and/or overexpressed in the majority of high-grade serous carcinomas. Determining whether these genes are upregulated in STICs is important in further elucidating the relationship of STICs to high-grade serous carcinomas and is fundamental in understanding the molecular pathogenesis of high-grade serous carcinomas. In this study, 37 morphologically defined STICs were obtained from 23 patients with stage IIIC/IV high-grade serous carcinomas. Both STICs and the high-grade serous carcinomas were analyzed for expression of Rsf-1 (HBXAP), cyclin E, fatty acid synthase (FASN) and mucin-4. In addition, they were examined for expression of established markers including p53, Ki-67 and p16. We found that diffuse nuclear p53 and p16 immunoreactivity was observed in 27 (75%) of 36 and 18 (55%) of 33 STICs, respectively, whereas an elevated Ki-67 labeling index (>or=10%) was detected in 29 (78%) of 37 STICs. Cyclin E nuclear staining was seen in 24 (77%) of 35 STICs, whereas normal tubal epithelial cells were all negative. Increased Rsf-1 and FASN immunoreactivity occurred in 63%, and 62% of STICs, respectively, compared with adjacent normal-appearing tubal epithelium. Interestingly, only one STIC showed increased mucin-4 immunoreactivity. Carcinomas, when compared with STICs, overexpressed p16, Rsf-1, cyclin E and FASN in a higher proportion of cases. In conclusion, STICs express several markers including Rsf-1, cyclin E and FASN in high-grade serous carcinomas. In contrast, mucin-4 immunoreactivity either did not change or was reduced in most STICs. These results suggest that overexpression of Rsf-1, cyclin E and FASN occurs early in tumor progression.
Department of Pathology, Legacy Health Systems, Portland, OR, USA.
Ann Smith
AS
Sehdev
Robert J
RJ
Kurman
Elisabetta
E
Kuhn
Ie-Ming
IeM
Shih
D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000737:chemistry* / Q000201:enzymology / Q000473:pathology; D019927:Cyclin E / Q000032:analysis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D005185:Fallopian Tube Neoplasms / Q000737:chemistry* / Q000201:enzymology / Q000473:pathology; D054890:Fatty Acid Synthase, Type I / Q000032:analysis*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D055264:Mucin-4 / Q000032:analysis; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000737:chemistry* / Q000201:enzymology / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis*; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000201:enzymology / Q000473:pathology; D015534:Trans-Activators / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D014408:Biomarkers, Tumor; D019927:Cyclin E; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; C524658:MUC4 protein, human; D055264:Mucin-4; D009687:Nuclear Proteins; C452851:RSF1 protein, human; C495901:TP53 protein, human; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I