Search

The Ovarian Task Force of the Gynecologic Cancer Steering Committee convened a clinical trials planning meeting on October 28-29, 2011, with the goals to identify key tumor types, associated molecular pathways, and biomarkers for targeted drug intervention; review strategies to improve early-phase screening, therapeutic evaluation, and comparison of new agents; and optimize design of randomized trials in response to an evolving landscape of scientific, regulatory, and funding priorities. The meeting was attended by international clinical and translational investigators, pharmaceutical industry representatives, government regulators, and patient advocates. Panel discussions focused on disease types, early-phase trials, and randomized trials. A manuscript team summarized the discussions and assisted with formulating key recommendations. A more integrated and efficient approach for screening new agents using smaller selective randomized trials in specific disease-type settings was endorsed, together with collaborative funding models between industry and the evolving national clinical trials network, as well as efforts to enhance public awareness and study enrollment through advocacy.

Establishing a diagnosis of ovarian clear cell carcinoma (O-CCC) can be subject to significant interobserver variation. Accurately diagnosing this tumor is important because of its chemoresistance and reported association with Lynch syndrome. The spectrum of the morphologic features of O-CCC has not been well described in a series composed of immunohistochemically characterized cases. A total of 155 cases diagnosed as O-CCC were retrieved from the files of 3 institutions to analyze architectural and cytologic features. The immunohistochemical features of these cases have been reported earlier. A comprehensive list of features was recorded, including, but not limited to, architectural patterns, nuclear appearance, cytoplasmic characteristics, and mitotic index. Between 1 and 13 slides were available for review for each case. The cases were divided into 2 groups based on morphologic characteristics, those with features shared by the large majority (the first group, n=138) and those that showed unusual characteristics (second group, n=17). Tumors in the first group typically showed a mixture of architectural patterns, the most frequent being papillary and tubulocystic. Papillae, usually small and round and lacking hierarchical branching and tufting or stratification of more than 3 cells, were present at least focally in almost 3 of 4 cases. The cell shape was predominantly cuboidal, not columnar. Nuclear pleomorphism and prominent nucleoli were frequently present, but never diffusely. Clear cytoplasm was found in nearly every case and hobnail cells were common. Mitoses exhibited a range from 0 to 13 with an average of 3 to 4 per 10 high power fields. The second group of tumors showed numerous unusual morphologic characteristics, despite the presence of clear cytoplasm, including those typically seen in other ovarian epithelial tumors, such as serous and endometrioid carcinoma. Eighty-nine percent of tumors from the first group showed the expected "O-CCC immunophenotype" [hepatocyte nuclear factor (HNF) positive, and estrogen receptor (ER), progesterone receptor (PR), Wilms tumor 1 (WT1) and p53 negative], whereas 4% of tumors showed HNF positivity along with focal ER or PR expression. Seven percent of tumors were not immunoreactive with these markers. Twenty-nine percent of tumors in the second group showed the O-CCC immunophenotype, whereas 24% of tumors were p53 positive, 5% of tumors were WT1 positive, and the remaining cases were negative for all markers. Ninety-seven percent (112 of 117) of HNF-positive tumors in this series were classical O-CCC. Therefore, O-CCC has characteristic morphologic features and a specific, if not unique, immunophenotype in the vast majority of the cases. Clear cell-rich tumors with features that depart from the classical morphologic appearances described herein should suggest the possibility of an alternative diagnosis.

Leiomyosarcomas are malignant smooth muscle tumors that occur most commonly in the gynecologic tract and soft tissue. There are different diagnostic criteria of malignancy for smooth muscle tumors arising at gynecologic and soft tissue sites and they may be managed differently but determining the primary site of a smooth muscle tumor can be difficult in some cases. In addition, the distinction between malignant and benign gynecologic tract smooth muscle tumors on morphologic grounds can be challenging. Using a series of tissue microarrays that contain 245 cases of leiomyosarcomas (102 gynecologic) with survival data, and 49 cases of uterine leiomyoma, we examined the ability of selected immune-markers (estrogen receptor (ER) and WT1) to distinguish between leiomyosarcomas of gynecologic and nongynecologic origin. In addition, we examined whether immunostains for p16, p53 and Ki-67 could distinguish between malignant and benign gynecologic smooth muscle tumors. ER nuclear positivity was observed in 3 and 50% of the nongynecologic and gynecologic leiomyosarcomas, respectively (P<0.001). Nuclear WT1 positivity was seen in 0 and 8% of the nongynecologic and gynecologic leiomyosarcomas, respectively (P<0.001). 87% of primary gynecologic leiomyosarcomas and 2% of uterine leiomyomas showed diffuse (>or=50% of cells) p16 staining (P<0.001). 23% of gynecologic leiomyosarcomas showed p53 immunopositivity (>or=50% of cells) whereas none of the leiomyomas were positive for p53 (P<0.001). 65% of the gynecologic leiomyosarcomas and 0% of the leiomyomas exhibited >10% Ki-67 proliferation index (P<0.001). Diffuse p16 and p53 immunopositivity and high Ki-67 proliferation index, singly or in combination, yielded an overall sensitivity of 92% and specificity of 98% for distinguishing between gynecologic leiomyosarcomas and leiomyomas and can be used as indicators of malignancy for gynecologic smooth muscle tumors. Although ER positivity can be used to support the gynecologic origin of a leiomyosarcomas, nuclear WT1 immunostaining is of little use.