Discordence of HER-2/neu overexpression and estrogen receptor between the primary breast cancer and axillary lymph node with metastasis
20106 Background: Adjuvant hormonal therapy and trastuzumab are known to be associated with a significant reduction in cancer-related mortality in a subset of women with breast cancer. The treatment decision is usually based on immunohistochemistry (IHC) staining of the primary tumor. We reported here a case of discordance of HER-2/neu overexpression and estrogen receptor status between the primary breast cancer and axillary lymph node with metastasis. Methods: IHC and fluorescence in situ hybridization (FISH) analysis was perfromed for the assessment of HER-2/neu. E-cadherin staining was done on the primary tumor and lymph node with metastasis. Results: A 52 year old woman presented with right breast lump. The imaging studies showed a 5 × 5 cm speculated mass. No other abnormalities were noted. An excision biopsy revealed 3 cm moderately differentiated invasive lobular carcinoma. Subsequently a wider excision and axillary lymph node dissection was done. 2/20 lymph nodes were involved by the cancer. IHC was done in the primary tumor and the lymph node with metastasis. IHC of the primary tumor revealed less than 1% nuclei positive for estrogen receptor (ER), 0% nuclei positive for progesterone receptor (PR), and no HER-2/neu overexpression. IHC of the lymph nodes with metastasis revealed 80% nuclei positive for ER, less than 1% nuclei positive for PR, and equivocal HER-2/neu overexpression. FISH analysis for HER-2/neu gene was done on the primary tumor which revealed no amplification in the tumor nuclei (Her2/CEP17 ratio was 3.6/2.7 = 1.3) whereas FISH analysis on the lymph node section revealed amplification in tumor nuclei (Her2/CEP 17 ratio of 7.3/1.9 = 3.9). E-cadherin staining of the primary breast tumor as well as the lymph node with metastasis revealed no membrane staining of the malignant cells in either section. Conclusions: The unusual occurrence of a divergent IHC profile and FISH analysis results between the primary carcinoma and metastatic carcinoma may be due to a subselection of a malignant clone which were not represented in the section of primary tumor chosen for IHC. Future studies are required to determine the utility of IHC staining of metastatic cells involving the lymph nodes if primary tumor is negative for HER-2/neu & ER. No significant financial relationships to disclose.