Fader, Amanda N.

Human epidermal growth factor receptor 2 (HER-2) targeted therapy shows promising results in HER-2-positive uterine serous carcinoma (USC). HER-2 scoring criteria for USC and its associated noninvasive lesion, serous endometrial intraepithelial carcinoma (SEIC), are not well-established. Here, we compare the breast and gastric (GI) HER-2 immunohistochemistry (IHC) scoring criteria for HER-2 with HER-2/neu fluorescence in situ hybridization (FISH) in 68 tumors (17 USC with SEIC, 30 USC, 18 SEIC, 3 metastatic USC). The majority (97%) of lesions displayed intratumoral HER-2 IHC heterogeneity. Breast or GI IHC scoring criteria were performed equivalently. The breast and GI IHC criteria classified 51% and 47% USC as HER-2 negative (IHC 0/1+), 40% and 45% as equivocal (IHC 2+), and 9% each as HER-2 positive (IHC 3+). A quarter of USC classified as HER-2 negative or positive with the breast (25%, n=7/28) or GI IHC criteria (23%, n=6/26) was discordant by FISH. Specifically, 13% to 14% of IHC 0/1+ USC were FISH amplified; 50% of IHC 3+ USC were FISH negative. The majority (77% to 83%) of SEIC were HER-2 IHC 0/1+, and no SEIC was HER-2 IHC 3+. A minority (4% to 7%) of IHC 0/1+ SEIC were FISH positive. Discordant HER-2 status was observed between half (47%,bn=7/15) of synchronous SEIC and USC. In conclusion, USC displays HER-2 intratumoral heterogeneity, a high IHC/FISH discordance rate, and variation in HER-2 status between the SEIC and invasive components. Caution is required when evaluating HER-2 in small biopsies, which should be repeated on excisions. Both IHC and FISH should be performed on USC until clinical trials correlate HER-2 status with clinical response to HER-2-targeted therapy.

The NCCN Guidelines for Cervical Cancer provide recommendations for diagnostic workup, staging, and treatment of patients with the disease. These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to first- and second-line systemic therapy recommendations for patients with recurrent or metastatic disease, and emerging evidence on a new histopathologic classification system for HPV-related endocervical adenocarcinoma.

Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.