Abstract P6-07-10: Cytogenetic analysis of squamous cell carcinoma of the breast reveals inter- and intra-tumoral heterogeneity
Authors: Oikawa M , Igawa A , Ishida M , Nakamura Y , Nishimura S , Koga C , Akiyoshi S , Koi Y , Taguchi K , Ohno S , Tokunaga E 
Published: May 2016

Background: Squamous cell carcinoma (SCC) of the breast is a rare and generally aggressive disease constituting less than 0.1 % of all breast carcinomas. Although they have distinct morphological features, the origin and cytogenetic profiles of SCCs are still not well understood. In this study, five cases of SCC of the breast, three of which had an SCC component and an invasive or noninvasive ductal carcinoma of no special type (NST) component, were analyzed to evaluate their cytogenetic inter- and intra-tumoral heterogeneity.

Methods: Using a pathological database of approximately 3,000 patients with breast cancer, five patients with SCC were identified. Their medical records were retrospectively reviewed to obtain clinicopathological, radiological, therapeutic and prognostic information. The area largely consisting of the SCC component was macro-dissected from five 10 μm-thick sections and tumor DNA was extracted using the QIAmp DNA Mini Kit (Qiagen). Three cases contained a component of invasive or noninvasive ductal carcinoma of NST as well as an SCC component, and tumor DNA from NST components were also extracted as described above. Tumor DNA from each case were used for array comparative genomic hybridization (aCGH) analysis using a high-density oligonucleotide microarray (Agilent® SurePrint G3 8x60k microarray) and the cytogenetic profiles of SCC components were compared with each other and in three of the five cases with their paired NST components.

Results: Sufficient amounts of DNA were obtained for aCGH analysis with an average of 0.78 μg (0.39–1.35 μg). The quality of the aCGH was acceptable, as judged by the mean derivative log ratio spread (DLRSpread) of 0.45 (0.20–0.55), which estimates the log ratio noise by calculating the spread of log ratio differences between consecutive probes along all chromosomes. The cytogenetic profiles of SCC components showed large inter-tumoral heterogeneity with between 2 and 160 copy number alterations per case and no common copy number alterations were found among cases. Meanwhile, cytogenetic profiles were almost identical between paired SCC and NST components,. However, in one case, a large number of copy number aberrant (CNA) regions were detected in the SCC component compared with the NST component and all aberrations in the NST component were also present in the SCC component, which implies that the SCC component originated from the NST component. There were no common SCC-component-specific aberrations in the three cases with NST components.

Conclusion: These results demonstrate the degree of cytogenetic inter- and intra-tumoral heterogeneity in SCC of the breast. The comparison of cytogenetic profiles in one case indicated that the SCC component originated from the NST component.

Citation Format: Oikawa M, Igawa A, Ishida M, Nakamura Y, Nishimura S, Koga C, Akiyoshi S, Koi Y, Taguchi K, Ohno S, Tokunaga E. Cytogenetic analysis of squamous cell carcinoma of the breast reveals inter- and intra-tumoral heterogeneity. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-07-10.