L1-CAM in Mucinous Ovarian Carcinomas and Borderline Tumors: Impact on Tumor Recurrence and Potential Role in Tumor Progression.

Mucinous ovarian carcinoma (MOC) is a rare histotype of primary ovarian carcinoma. Frequent pathogenic molecular alterations include mutations in KRAS , TP53 , and overexpression of human epidermal growth factor receptor 2, but without having prognostic relevance. As L1-CAM (cell adhesion molecule) has previously shown prognostic relevance in other epithelial tumors of the female genital tract, we analyzed whether L1-CAM expression affected MOC prognosis. In addition, we investigated L1-CAM expression in mucinous borderline tumors (MBOTs) with and without adjacent MOC to identify its potential role in the pathogenesis of MOC. We examined a well-characterized collective of 39 MOCs by immunohistochemistry and compared their expression with clinicopathologic data. L1-CAM positivity was defined as any (even single-cell) positivity. Furthermore, we compared the L1-CAM expression in 20 MBOT regions adjacent to a MOC with that of 15 pure MBOTs. L1-CAM expression in MOC was significantly associated with recurrence, independent of tumor stage. Overall, 7/20 positive cases recurred versus 0/19 L1-CAM-negative cases ( P =0.032), showing a significant difference in time to progression. Furthermore, the presence of at least 1 defined molecular alteration (L1-CAM, aberrant p53, or human epidermal growth factor receptor 2) was found more frequently in the MBOT regions adjacent to a MOC (14/20) than in pure MBOTs (3/15) ( P =0.024). Expression of the tumor marker L1-CAM is frequent (51%) in MOC and is associated with tumor recurrence. The lack of L1-CAM may serve to characterize cases with a low risk of recurrence. Furthermore, the presence of specific molecular alterations in MBOTs is associated with adjacent carcinomas and may define potential pathways in tumor progression.

Recurrence Score® Result Impacts Treatment Decisions in Hormone Receptor-Positive, HER2-Negative Patients with Early Breast Cancer in a Real-World Setting-Results of the IRMA Trial.

BACKGROUND: Patients with hormone receptor-positive (HR+), HER2-negative (HER2-) early breast cancer (eBC) with a high risk of relapse often undergo adjuvant chemotherapy. However, only a few patients will gain benefit from chemotherapy. Since classical tumor characteristics (grade, tumor size, lymph node involvement, and Ki67) are of limited value to predict chemotherapy efficacy, multigene expression assays such as the Oncotype DX® test were developed to reduce over- and undertreatment. The IRMA trial analyzed the impact of Recurrence Score® (RS) assessment on adjuvant treatment recommendations. MATERIALS AND METHODS: The RS result was assessed in patients with HR+/HER2- unilateral eBC with 0-3 pathologic lymph nodes who underwent primary surgical treatment at the Department for Women's Health of Tuebingen University, Germany. Therapy recommendations without knowledge of the RS result were compared to therapy recommendations with awareness of the RS result. RESULTS: In total, 245 patients underwent RS assessment. Without knowledge of the RS result, 92/245 patients (37.6%) would have been advised to receive chemotherapy. After RS assessment, 56/245 patients (22.9%) were advised to undergo chemotherapy. Chemotherapy was waived in 47/92 patients (51.1%) that were initially recommended to receive it. Chemotherapy was added in 11/153 patients (7.2%) that were recommended to not receive it initially. SUMMARY: Using the RS result to guide adjuvant treatment decisions in HR+/HER2- breast cancer led to a substantial reduction of chemotherapy. In view of the results achieved in prospective studies, the RS result is among other risk-factors suitable for the individualization of adjuvant systemic therapy.

CD56 (Neural Cell Adhesion Molecule) Expression in Ovarian Carcinomas: Association With High-Grade and Advanced Stage But Not With Neuroendocrine Differentiation.

OBJECTIVE: Neural cell adhesion molecule (CD56) has been proposed as a potential marker for neuroendocrine differentiation in carcinomas, together with synaptophysin and chromogranin A. However, CD56 immunoreactivity by itself can be found in a broad variety of tumors, including ovarian neoplasms. CD56 has recently been suggested as a potential target for antibody-based therapy. However, for ovarian carcinoma, there is only limited data available regarding the pattern of CD56 immunoreactivity, coexpression of neuroendocrine markers, and correlation with histological types and clinical parameters. METHODS: In our study, we therefore evaluated CD56 staining by immunohistochemistry on a tissue micrroarray with 206 ovarian carcinomas, including 151 high-grade serous, 7 low-grade serous, 32 endometrioid, 11 clear cell, 5 mucinous, as well as 33 atypically proliferating serous tumors/serous borderline tumors. RESULTS: At least focal CD56 immunoreactivity was observed in 65% of carcinomas of all histological types. Moderate staining with at least 10% positive cells was found in 44 (28%) high-grade serous carcinomas (HGSOCs), 2 (29%) low-grade serous and 3(9%) endometrioid carcinomas. Strong immunoreactivity was limited to 10 (7%) HGSOCs. There was no correlation with the expression of chromogranin or synaptophysin. Serous borderline tumors showed only weak and focal staining in 11 (33%). Expression of CD56 overall was significantly associated with high-grade and advanced stage. In the subgroup of HGSOCs, CD56 expression was associated with reduced overall survival (median 30 vs. 47 months, P = 0.039, log rank, univariate analysis). CONCLUSIONS: CD56 (neural cell adhesion molecule) is frequently expressed in ovarian carcinomas and is significantly associated with HGSOC and advanced tumor stage. Due to its lack of correlation with neuroendocrine differentiation, CD56 expression is of limited diagnostic value, but may rather serve as a marker for tumor progression or as a potential therapeutic target.