Discordance rate of HER2 status in primary breast carcinomas versus synchronous axillary lymph node metastases: a multicenter retrospective investigation

Abstract

BackgroundHuman epidermal growth factor receptor 2 (HER2) is considered to be a therapeutic and prognostic marker in the management of breast carcinoma (BC), although discordance rates between primary and metastatic or locally recurrent lesions have been reported.MethodsOne hundred and forty-eight paraffin-embedded BC tissues from patients of mean age 59.27 (33–96) years and corresponding synchronous lymph node metastases were collected and retrospectively studied using immunohistochemistry and fluorescence in situ hybridization to evaluate HER2 status. Fleiss-Cohen weighted k statistics were used to assess the concordance rate between HER2 status of the primary BC and the synchronous metastatic lesions.ResultsThe overall concordance rate for HER2 was 95.28%. Eighty-nine cases were concordantly HER2-negative in primary BC and nodal metastases, and 52 cases were HER2-positive in both primary and metastatic tumors. Changes in HER2 status between primary BC and corresponding synchronous metastases were observed in seven (4.72%) cases. Three of the discordant cases were HER2-negative in the primary tumor and HER2-positive in the metastases, while four cases were HER2-positive in the primary BC and HER2-negative in the metastases. No significant correlations were identified between HER2 status and expression of hormone receptors, growth fraction (Ki-67), or other histopathological parameters (pT, pN, grade).ConclusionSimultaneous determination of HER2 in BC and corresponding metastatic lymph nodes is not mandatory, but may strongly influence the therapeutic management. It was demonstrated that loss of HER2 amplification results in worse post-relapse survival and overall survival in BC patients and, on the other hand, a gain in HER2 expression in metastatic lymph nodes of BC may allow the possibility of a targeted treatment. Thus, our opinion is that significant prognostic information may be obtained by simultaneous assessment of HER2 status in both primary and synchronous metastatic BC.

HER2 Analysis in Sporadic Thyroid Cancer of Follicular Cell Origin

“…Indeed, a similarly wide variation in HER2 overexpression has been reported in many other tumor types [3,4,5,6,7,8]. Therefore, as the prognostic and therapeutic relevance of HER2 status has grown, the need to achieve a standardized HER2 assessment method has also arisen in neoplastic sites different from the stomach and breast [11].…”

“…The HER2 gene is frequently amplified and the protein overexpressed in several human epithelial malignancies, including breast, gastric, ovarian, and colon-rectal cancers [3,4,5,6,7,8,9]. In such tumors, HER2 amplification/overexpression has been linked to a poor overall outcome and a poorly differentiated phenotype [3,4,5,6,7].…”

“…In such tumors, HER2 amplification/overexpression has been linked to a poor overall outcome and a poorly differentiated phenotype [3,4,5,6,7]. It has also been considered a useful indicator of response to specifically targeted therapies, such as trastuzumab, that inhibit the extracellular domain of HER2 [8,9].…”

Establishment and characterization of patient-derived tumor xenograft using gastroscopic biopsies in gastric cancer

“…Immunohistochemistry (IHC) stainings of HER2 was performed using anti-HER2/neu antibody (4B5, Roche, Basel, Switzerland) according to a previous report 31 . H&E staining and IHC staining were reviewed and scored according to the criteria reported previously 32 by two independent pathologists who were blinded to this study.…”

HER2 Status in Premalignant, Early, and Advanced Neoplastic Lesions of the Stomach

“…On the other hand, negative conversion observed in metastatic deposits of patients who had not received any neoadjuvant treatments [ 108 ] cannot develop as the result of resistance to Trastuzumab therapy. Of note, discrepancy in HER2 status between primary tumor and paired nodal metastases was already highlighted in breast cancer [ 106 , 107 ]. Although at present there is no indication of testing HER2 status in synchronous nodal metastases from GC, possible discordance in HER2 expression in metastatic tumors compared to primitive cancer is relevant for the therapeutic management and prognosis of the patients.…”