Negative genic switch of HER-2 in the primary tumor instead of the synchronous metastatic nodal lesions after neoadjuvant chemotherapy in a patient with primary HER2-positive breast cancer.

BACKGROUND: A few retrospective studies have indicated that neoadjuvant chemotherapy (NAC) in breast cancer may change biomarker profiles of the primary tumor. Little is known about the status of HER-2 gene of the synchronous nodal metastases when that of the residual tumor undergoes negative conversion in a neoadjuvant setting. CASE PRESENTATION: We describe a female patient with left breast cancer (T2N2M0) who underwent negative conversion of HER-2 in the primary tumor instead of the synchronous nodal lesions after NAC. Core needle biopsy showed invasive ductal carcinoma with HER2 immunohistochemistry (IHC) (2+) and amplified HER-2 gene determined by fluorescence in situ hybridization (FISH). Then, the patient underwent 4 cycles of anthracycline- and taxane-based NAC and subsequent left modified radical mastectomy. Postoperative pathology showed invasive ductal carcinoma involving 4 of 12 surgically excised axillary lymph nodes with HER2 IHC (1+) and FISH negative (HER2 gene not amplified) in the residual tumor of the breast specimen. Due to the negative genic switch of HER2 after NAC, the patient rejected to accept trastuzumab. Under the patient's consent, the synchronous nodal lesions were further investigated and showed HER2 IHC(-) but FISH positive (HER-2 gene amplified). Therefore, the patient agreed to accept adjuvant trastuzumab treatment every 3 weeks for 1 year. CONCLUSIONS: We propose further assessment of HER2 gene in the synchronous nodal metastases, especially when negative genic switch of HER-2 occurs in the primary tumor after NAC in order to tailor the systemic regimens for breast cancer patients.

FTH1 binds to Daxx and inhibits Daxx-mediated cell apoptosis.

As a highly conserved nuclear protein, death domain-associated protein (Daxx) plays an important role in transcriptional control, carcinogenesis, and resistance to virus infection and so on. In order to further investigate the mechanism of Daxx, the yeast two-hybrid technique was used to screen the intra-cellular proteins interacting with Daxx. And 13 positive colonies and three proteins interacting with Daxx were obtained. One of the candidate proteins was identified as ferritin, heavy polypeptide 1(FTH1). The interaction between Daxx and FTH1 was further supported by GST pull-down and co-immunoprecipitation respectively. Then Daxx was determined to induce apoptosis and FTH1 can inhibit Daxx-mediated apoptosis. Besides, it is found that Daxx mediated apoptosis through the Fas-Daxx-ASK1-JNK1 signaling pathway, while FTH1 can inhibit the activation of JNK signaling pathway. We present evidence to demonstrate the FTH1 and Daxx are able to participate in apoptosis pathway through JNK signal molecule and FTH1 can inhibit this pathway.