Eike Burandt1, Martin Grünert2, Annette Lebeau2, Matthias Choschzick2, Alexander Quaas2, Fritz Jänicke3, Volkmar Müller3, Ursula Scholz3, Carsten Bokemeyer4, Cordula Petersen5, Stefan Geist6, Peter Paluchowski6, Christian Wilke7, Uwe Heilenkötter8, Ronald Simon2, Guido Sauter2, Waldemar Wilczak2. 1. Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. e.burandt@uke.de. 2. Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. 3. Department of Gynecology, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany. 4. Department of Internal Medicine II, Oncology Center, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany. 5. Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany. 6. Department of Gynecology, Regio Clinic Pinneberg, 25421, Pinneberg, Germany. 7. Department of Gynecology, Regio Clinic Elmshorn, 25337, Elmshorn, Germany. 8. Department of Gynecology, Clinical Centre Itzehoe, 25524, Itzehoe, Germany.
Abstract
BACKGROUND: Cyclin D1 (CCND1) gene amplification is a molecular key alteration in breast cancer and was suggested to predict resistance to antihormonal therapy. As tissue heterogeneity may affect diagnostic accuracy of predictive biomarkers, CCND1 genetic heterogeneity was assessed in this study. A novel tissue microarray (TMA) platform was manufactured for this purpose. METHODS: Primary breast carcinomas from 147 patients were sampled in a "heterogeneity-TMA" by taking eight different tissue cores from 4 to 8 tumor-containing blocks per case. Additional tissue samples were taken from 1 to 4 corresponding nodal metastases in 35 of these patients. CCND1 amplification was assessed by fluorescence in situ hybridization (FISH). RESULTS: CCND1 amplification was seen in 28 of 133 (21.05 %) informative patients. Amplification was significantly associated with high tumor grade (p = 0.042), but unrelated to tumor type (p = 0.307), stage (p = 0.540) and ER (p = 0.061) or PR (p = 0.871) expression. A discordant Cyclin D1 amplification status was detected in 6 out of 28 (21.43 %) amplified tumors by heterogeneity-TMA analysis. Re-testing on large sections revealed three patients with true heterogeneity of high-level CCND1 amplification and another three patients with variable interpretation of borderline FISH ratios ranging between 1.7 and 2.3. No discrepancies were detected between 22 primary tumors and their matched lymph node metastases. CONCLUSIONS: The high degree of homogeneity seen for CCND1 amplification suggests that this alteration is an early event in the development of a small subset of breast cancers.
BACKGROUND:Cyclin D1 (CCND1) gene amplification is a molecular key alteration in breast cancer and was suggested to predict resistance to antihormonal therapy. As tissue heterogeneity may affect diagnostic accuracy of predictive biomarkers, CCND1 genetic heterogeneity was assessed in this study. A novel tissue microarray (TMA) platform was manufactured for this purpose. METHODS: Primary breast carcinomas from 147 patients were sampled in a "heterogeneity-TMA" by taking eight different tissue cores from 4 to 8 tumor-containing blocks per case. Additional tissue samples were taken from 1 to 4 corresponding nodal metastases in 35 of these patients. CCND1 amplification was assessed by fluorescence in situ hybridization (FISH). RESULTS:CCND1 amplification was seen in 28 of 133 (21.05 %) informative patients. Amplification was significantly associated with high tumor grade (p = 0.042), but unrelated to tumor type (p = 0.307), stage (p = 0.540) and ER (p = 0.061) or PR (p = 0.871) expression. A discordant Cyclin D1 amplification status was detected in 6 out of 28 (21.43 %) amplified tumors by heterogeneity-TMA analysis. Re-testing on large sections revealed three patients with true heterogeneity of high-level CCND1 amplification and another three patients with variable interpretation of borderline FISH ratios ranging between 1.7 and 2.3. No discrepancies were detected between 22 primary tumors and their matched lymph node metastases. CONCLUSIONS: The high degree of homogeneity seen for CCND1 amplification suggests that this alteration is an early event in the development of a small subset of breast cancers.
Entities:
Keywords:
Breast cancer; Cyclin D1; FISH; Heterogeneity; Heterogeneity-TMA
Authors: Vandna Shah; Salpie Nowinski; Dina Levi; Irek Shinomiya; Narda Kebaier Ep Chaabouni; Cheryl Gillett; Anita Grigoriadis; Trevor A Graham; Rebecca Roylance; Michael A Simpson; Sarah E Pinder; Elinor J Sawyer Journal: Breast Cancer Res Date: 2017-01-17 Impact factor: 6.466