Figure 1 | Modern Pathology

Figure 1

From: Molecular determination of the clonal relationships between multiple tumors in BRCA1/2-associated breast and/or ovarian cancer patients is clinically relevant

Figure 1Figure 1

Conventional diagnostics and molecular analysis results for case no. 1. Case no. 1 presented with tumors of the right (T1) and the left (T2) breast, and a tumor in the lung 7 years later (T3). (a). Both tumors in the breast (T1 and T2) could be conclusively diagnosed invasive ductal carcinoma of the breast based on haematoxylin and eosin (H&E) stainings only. Additionally, ER and HER2NEU stainings are shown, which were negative in both tumors. Conclusive diagnosis regarding the origin of the non-small cell carcinoma in the lung (T3) based on HE stainings and immunohistochemistry (P63 and TTF1 both negative) was not possible. As part of the molecular analysis p53 immunohistochemistry was performed, showing strong nuclear expression in the tumor cells of T1 and T3, and absent expression in the tumor cells of T2. Scale bars represent 50 μm. (b). Targeted next generation sequencing results of TP53 exon 6 for DNA isolated from normal and tumor tissues of the patient. Each grey line represents an individual read; only aberrations from the wildtype sequence are indicated. Sequencing results are shown in reverse complement, which means that TCG is actually CGA. T1 and T3 show an identical PT53 missense mutation (c.646G>A; p.V216M), whereas T2 shows a different TP53 nonsense mutation (c.637C>T; p.R213*). (c). Loss of heterozygosity was analyzed using single nucleotide polymorphisms, the variant allele frequencies of 17 single nucleotide polymorphisms at 5 different loci (chromosome 8p, PTEN, BRCA2, BRCA1 and SMAD4) are shown for the three tumor samples. Loss of the reference allele is indicated in red and loss of the variant allele in green; a more intense color (either red or green) indicates a higher tumor percentage. As expected for a BRCA1 germline mutation carrier, all tumor samples show loss of the same BRCA1 allele. For all other loci shown, T1 and T3 show corresponding loss of heterozygosity patterns (both tumors show either red or green), whereas T2 shows a different loss of heterozygosity pattern. Chr: Chromosome.

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