Correspondence

Dicer and Drosha in Ovarian Cancer

N Engl J Med 2009; 360:1150-1151March 12, 2009

Article

To the Editor:

Merritt et al. (Dec. 18 issue)1 report finding a relation between prognosis and the expression of Dicer and Drosha in women with ovarian carcinoma of unstated histologic subtype. The histologically defined subtypes of ovarian carcinoma (high-grade serous, clear cell, endometrioid, mucinous, and low-grade serous) are distinct diseases that can be reproducibly diagnosed2 and that vary with respect to characteristics of the precursor lesions, the genetic events during oncogenesis,3 outcome,2,4 and response to chemotherapy.4 These subtypes have distinct biomarker-expression profiles.5 In cohorts of patients with ovarian carcinoma consisting of a mixture of subtypes, biomarkers preferentially expressed by specific subtypes often have prognostic or other clinical associations for the entire cohort that are not significant after correction for subtype. We therefore ask whether Dicer and Drosha expression levels correlate with histologic subtype and whether their prognostic significance and association with tumor stage and optimal type of cytoreduction hold true within each subtype.

Martin Köbel, M.D.
University of British Columbia, Vancouver, BC V5Z 1M9, Canada

C. Blake Gilks, M.D.
Vancouver General Hospital, Vancouver, BC V5Z 1M9, Canada

David G. Huntsman, M.D.
British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada
dhuntsma@bccancer.bc.ca

5 References

1. 1

   Merritt WM, Lin YG, Han LY, et al. Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med 2008;359:2641-2650
   Full Text | Web of Science | Medline

2. 2

   Gilks CB, Ionescu D, Kalloger SE, et al. Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma. Hum Pathol 2008;39:1239-1251
   CrossRef | Web of Science | Medline

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   Crum CP, Drapkin R, Miron A, et al. The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol 2007;19:3-9
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   Fountain J, Trimble E, Birrer MJ. Summary and discussion of session recommendations. Gynecol Oncol 2006;103:Suppl 1:S23-S25
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   Kobel M, Kalloger SE, Boyd N, et al. Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med 2008;5:e232-e232
   CrossRef | Web of Science | Medline

Author/Editor Response

In response to the letter from Köbel et al.: with regard to histologic subtypes of ovarian cancer, 109 of the 111 samples (98.2%) we tested had serous histologic characteristics. Removing the two nonserous samples from analyses did not change our results significantly.

With regard to grade, 93 of the 111 samples (83.8%) were high-grade serous tumors and 16 (14.4%) were low-grade serous tumors. In the article, a decreased Dicer messenger RNA level was an independent predictor of survival after adjustment for traditional clinical variables. On analysis of high-grade serous samples only, the median overall survival remained poor for patients with low Dicer expression (2.16 years, vs. 9.25 years for those with high Dicer expression; P<0.001) or low Drosha expression (2.66 years, vs. 7.92 years for those with high Drosha expression; P=0.008). In multivariate analyses of those samples (see Table 3 in the article for the list of variables), low Dicer expression remained an independent predictor of poor survival (hazard ratio for death, 2.33; 95% confidence interval, 1.19 to 4.55; P=0.01).

We agree that the significance of Dicer and Drosha in less common histologic subtypes of ovarian cancer would be of interest. Nevertheless, our findings have implications for patients with ovarian and other cancers.1-4

William M. Merritt, M.D.
Diana L. Urbauer, M.S.
Anil K. Sood, M.D.
M.D. Anderson Cancer Center, Houston, TX 77230-1439
asood@mdanderson.org

4 References

1. 1

   Halder J, Kamat AA, Landen CN Jr, et al. Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy. Clin Cancer Res 2006;12:4916-4924
   CrossRef | Web of Science | Medline

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   Nelson KM, Weiss GJ. MicroRNAs and cancer: past, present, and potential future. Mol Cancer Ther 2008;7:3655-3660
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   Landen CN Jr, Chavez-Reyes A, Bucana C, et al. Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Res 2005;65:6910-6918
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4. 4

   Merritt WM, Lin YG, Spannuth WA, et al. Effect of interleukin-8 gene silencing with liposome-encapsulated small interfering RNA on ovarian cancer cell growth. J Natl Cancer Inst 2008;100:359-372
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Martin Köbel, Steve E. Kalloger, David G. Huntsman, Jennifer L. Santos, Kenneth D. Swenerton, Jeffrey D. Seidman, C. Blake Gilks. (2010) Differences in Tumor Type in Low-stage Versus High-stage Ovarian Carcinomas. International Journal of Gynecological Pathology 29:3, 203-211
   CrossRef