Molecular profiling in early stage IB1 squamous cell carcinomas of the uterine cervix.



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Treatment of tumors of the cervix is based on clinical staging of disease. The International Federation of Gynaecology and Obstetrics system (FIGO staging) has established a system whereby cervical cancers are staged on the basis of anatomical extent of the tumor. Microinvasive tumors most often require non-radical surgical resection and pose little risk of recurrence and metastasis. On the other extreme, cancers that are inoperable, due to spread beyond the cervix (Stage IIB to IVB) require concomitant chemotherapy and radiation therapy. Currently, of all women undergoing radical hysterectomies and pelvic lymphadenectomy for FIGO stage IB1 carcinomas, forty to fifty percent are deemed at risk for recurrence and require radiation therapy and chemotherapy 1. Much research has focused on linking histologic phenotype to outcome. However, tumor heterogeneity has made predictions of recurrence risk difficult. Ten percent of patients deemed having a low risk of recurrence by histological criteria will present with recurrent tumors within 5 years. The problem is that women may not receive optimal radiation therapy. If under treated, the cancer comes back. If over-treated there is a risk of toxicity associated with the adjuvant therapy. \r\nThe overall purpose of this research was to clarify the molecular mechanisms of progressive IB1 cervical disease in order to stratify risk to better match multi-modality therapy to minimize morbidity, mortality, and costs. The goal is to improve characterization of the tumor to individualize therapy. \r\nMolecular profiling was used to identify a group of 98 genes that differentiate early cancers with a low risk of recurrence from those with a high risk of recurrence. Tumor heterogeneity is an important consideration when using molecular profiling to characterize outcome. There are location-specific genes that can be used for elucidating the mechanism of disease and individualizing patient care. \r\nGeneChip technology is a powerful tool for teasing out the orchestration of molecular processes leading to progressive disease. As the molecular signature technology develops, we can move beyond improved diagnosis to improved therapy. This preliminary analysis may help to identify improved markers for predicting outcome so we can offer patients more precisely tailored treatment regimens.\r\n