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Clear Cell Tumors Have Higher mRNA Levels of ERCC1 and XPB Than Other Histological Types of Epithelial Ovarian Cancer

Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, Morgantown, West Virginia [E. R., J. J. Y.]; John F. Donahue Graduate School of Business, Duquesne University, Pittsburgh, Pennsylvania [A. D.]; and Parabon Computation, Inc., Fairfax, Virginia [J. G., S. L. A.]

Purpose: The purpose of the present work was to investigate the relationship between mRNA expression of ERCC1 and XPB, two key genes in the nucleotide excision repair pathway, and clinical resistance of platinum-chemotherapy in histological subtypes of epithelial ovarian cancer.

Experimental Design: mRNA levels of ERCC1 and XPB in epithelial ovarian cancer specimens from 126 different individuals were assessed using reverse transcription-PCR and followed by Southern hybridization methodology. Data were analyzed by linear regression analyses and by exhaustive regression analyses.

Results: Five different histological types of tumors were examined; serous (n = 76), mucinous (n = 11), clear cell (n = 9), poorly differentiated (n = 9), and endometroid (n = 21). Numerical values for mRNA expression levels were based on internal controls for a stable comparative cell line and for ß-actin. Median values for ERCC1 and XPB mRNAs within clear cell tumors were, on average, >2-fold higher than the other histological tumor types. Linear regression analyses suggest a continuum of nucleotide excision repair gene expression among these cell types, and exhaustive regression analyses demonstrate that the higher mRNA levels seen in clear cell tumors are highly statistically significant.

Conclusions: We conclude that mRNA levels of ERCC1 and XPB tend to be higher in clear cell tumors as opposed to other types of epithelial ovarian cancer. This is consistent with the long-standing observation that clear cell tumors are more likely to show de novo drug resistance against DNA damaging agents in the clinic.

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