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Ki-67 Labeling Index as an Adjunct in the Diagnosis of Serous Tubal Intraepithelial Carcinoma

Kuhn, Elisabetta M.D.; Kurman, Robert J. M.D.; Sehdev, Ann Smith M.D.; Shih, Ie-Ming M.D., Ph.D.

International Journal of Gynecological Pathology:
doi: 10.1097/PGP.0b013e31824cbeb4
Pathology of the Upper Genital Tract: Original Articles
Abstract

There is mounting evidence that serous tubal intraepithelial carcinoma (STIC) may be the immediate precursor of ovarian high-grade serous carcinoma (HGSC) but the criteria for its diagnosis are not well established as highlighted in a recent study showing that interobserver reproducibility, even among expert gynecologic pathologists, was moderate at best. Given the clinical significance of a diagnosis of STIC in a patient who has no other evidence of ovarian carcinoma, this is a serious issue that we felt needed to be addressed. Although it is not clear, at this time, whether such a patient should or should not be treated, the importance of an accurate and reproducible diagnosis of precursors of ovarian carcinoma cannot be underestimated. We hypothesized that an elevated Ki-67 labeling index may aid the diagnosis of STIC. Accordingly, we compared the Ki-67 index of STIC and HGSC to normal fallopian tube epithelium (FTE) in the same patients and to a control group of patients without carcinoma, matched for age. A total of 41 STICs were analyzed, of which 35 were associated with a concurrent HGSC. In FTE, immunoreactivity for Ki-67 was restricted to a few scattered cells (mean 2.0%). No statistically significant difference was found between patients with and without HGSC (P>0.05). However, both STICs and HGSC had significantly higher Ki-67 indices than normal FTE (P<0.0001). STICs uniformly had an elevated Ki-67 labeling index that ranged from 11.7% to 71.1% (average 35.6%). There was no correlation of the Ki-67 labeling index in the STICs and the associated HGSC, as the labeling index was lower in STIC in 18/35 (51.4%) whereas it was higher in 17/35 (48.6%) (P=0.86). In conclusion, the findings in this study indicate that compared with FTE, STICs have a significantly higher Ki-67 index similar to HGSC. Accordingly, the Ki-67 index can aid the diagnosis of intraepithelial tubal proliferations suspicious for STIC. Therefore, we propose that a Ki-67 index of 10% is a useful diagnostic tool to distinguish STICs from normal FTE.

Author Information

Departments of Pathology (E.K., R.J.K., I-M.S.)

Gynecology and Obstetrics (R.J.K., I-M.S.)

Oncology (R.J.K., I-M.S.), the Johns Hopkins Medical Institutions, Baltimore, Maryland

Department of Pathology (A.S.S.), Legacy Health Systems, Portland, Oregon

This study is supported by a CDMRP Ovarian Cancer Consortium grant (OC100517) from the US Department of Defense.

The authors declare no conflict of interest.

Address correspondence and reprint requests to Ie-Ming Shih, MD, PhD, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231. E-mail: ishih@jhmi.edu.

©2012International Society of Gynecological Pathologists