This study is the first comprehensive, integrated approach to examine grade-specific changes in gene expression along the entire neoplastic spectrum of cervical intraepithelial neoplasia (CIN) in the process of cervical carcinogenesis. This was accomplished by identifying gene expression signatures of disease progression using cDNA microarrays to analyze RNA from laser-captured microdissected epithelium and underlying stroma from normal cervix, graded CINs, cancer, and patientmatched normal cervical tissues. A separate set of samples were subsequently validated using a linear mixed model that is ideal to control for interpatient gene expression profile variation, such as age and race. These validated genes were ultimately used to propose a genomically based model of the early events in cervical neoplastic transformation. In this model, the CIN 1 transition coincides with a proproliferative/immunosuppression gene signature in the epithelium that probably represents the epithelial response to human papillomavirus infection. The CIN 2 transition coincides with a proangiogenic signature, suggesting a cooperative signaling interaction between stroma and tumor cells. Finally, the CIN 3 and squamous cell carcinoma antigen transition coincide with a proinvasive gene signature that may be a response to epithelial tumor cell overcrowding. This work strongly suggests that premalignant cells experience a series of microenvironmental stresses at the epithelium/ stroma cell interface that must be overcome to progress into a transformed phenotype and identifies the order of these events in vivo and their association with specific CIN transitions. [Cancer Res 2007;67(15):7113-23]

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There are approximately 9.1 pelvic surgeries performed for every histologically confirmed adnexal malignancy in the United States, compared to 2.3 surgeries per malignancy (in oncology centers) and 5.9 surgeries per malignancy (in other centers) in Europe. An important prognostic factor in the long-term survival in patients with ovarian malignancy is the initial management by a gynecological oncologist. With high accuracy of imaging for adnexal mass characterization and consequent appropriate triage to subspecialty referral, the better use of gynecologic oncology can improve treatment outcomes. Ultrasound, including transabdominal, transvaginal, and duplex ultrasound, combined with MRI with contrast can diagnose adnexal masses as benign with specific features (ie, functional masses, dermoid, endometrioma, fibroma, pedunculated fibroid, hydrosalpinx, peritoneal inclusion cyst, Tarlov cyst), malignant, or indeterminate.