Utility of clinical markers to identify patients with high risk cervical dysplasia and cancer

Abstract

10055 Background: The natural history of cervical neoplasias appears unpredictable with 1/3 to 1/2 of CIN lesions regressing without intervention; therapeutic targeting aids in screening and selecting patients at risk and elucidating treatment response. This study aimed at determining if a pattern of tumor suppressor, oncogene, and growth factor expression (specifically HER-2/neu, progesterone and estrogen receptors (ER/PR), p53, and Ki67) exists in the progression of cervical cancer utilizing the widely applicable process of immunohistochemistry. Methods: Paraffin sections from 128 cervical biopsy, cone, and hysterectomy specimens collected from 1/00–12/04 were obtained from the surgical pathology repository at a tertiary care center with a primarily Asian and Polynesian patient population. Levels of expression in normal, low and high grade dysplasias, and invasive carcinomas were measured via automated immunohistochemical analysis. Results: 30% of samples came from patients who smoked. Ki-67 index rose with increasing dysplastic change (17–43%) but dropped with invasive carcinomas (<17%). HER-2/neu staining occurred at greater levels in high grade lesions and invasive carcinomas but average intensity measured <1, with >2.2 being of prognostic significance because of candidacy for Herceptin therapy by breast criteria. ER/PR expression generally remained low with a penchant for parabasal cells (2–14%), and p53 levels likewise appeared minimally affected (3–5%). Conclusions: While HPV infection immortalizes cervical cells via a p53/pRb pathway, the equivocal expression of wild-type p53 across pre-invasive and more aggressive lesions suggests the involvement of other environmental toxins and genetic mutations. PR and ER play only a minor role in the development of adenosquamous carcinomas, indicating a lack of hormonal control in cervical tumor growth and proliferation. Her-2/neu, however, participates in the late events of cervical malignancy but at such levels that clinical usefulness proves questionable. Although HER-2/neu perhaps holds limited prognostic value in cervical carcinogenesis, similar molecular pathways independent of HPV need to be investigated as adjuncts to the common Pap smear. No significant financial relationships to disclose.