Expression of Immunohistochemical Markers before and after Neoadjuvant Chemotherapy in Breast Carcinoma, and Their Use as Predictors of Response

Abstract

PurposeFor patients with breast carcinoma, immunohistochemical markers are important factors in determining the breast cancer subtype and for establishing a therapeutic plan, including the use of neoadjuvant chemotherapy (NACT). However, it is not clear whether the expression of certain markers changes after NACT.MethodsWe assessed estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, p53, and Bcl-2 expression in specimens from 345 breast cancer cases before and after NACT. We analyzed the association between response to NACT and the expression of the markers in pre-NACT specimens. We also compared the expression between pre- and post-NACT specimens.ResultsER and PR expression was negatively associated with pathological complete response (pCR). HER2 was associated with pCR in all cases, but the association was lost when the cases were subdivided according to hormone receptor status. The pre-NACT tumor size of cases with pCR after NACT was smaller than that of cases with residual disease. HER2-enriched and triple-negative breast cancers were more likely to achieve pCR than luminal A type cancers. PR expression and the Ki-67 index decreased after NACT. A decrease in the Ki-67 index was also demonstrated in hormone receptor positive and HER2-enriched subtypes, but no similar tendency was observed in the triple-negative subtype.ConclusionA patient with breast cancer scheduled for NACT should be assessed for the breast cancer subtype, as this will influence the treatment plans for the patient. The expression of PR and Ki-67 after NACT should be interpreted carefully because NACT tends to reduce the expression of these molecules.

CK19 expression in breast tumours and lymph node metastasis after neoadjuvant therapy

“…Is CK19 still a good target for detecting metastatic cells on lymph nodes after systemic therapy? This question arises because of the demonstration of IHC alterations of different markers, such as SP1, lactoalbumin, and hormonal receptors, on breast cancer cells after treatment . CK19 is a luminal epithelial cell marker expressed by most (96.9–98.2%) breast cancer cells, but not by haematopoietic cells .…”

“…According to previous studies, the immunohistochemical (IHC) expression pattern and intensity of different biomarkers may be altered after chemotherapy. [11][12][13][14][15][16] On the basis of these findings, breast cancer epithelial markers, such as CK19, might undergo similar changes, and consequently CK19 should not be used as a target to search for metastatic cells; however, whether these changes occur has not been evaluated until the present study.…”

The G-Protein Coupled Estrogen Receptor (GPER/GPR30) in ovarian granulosa cell tumors

“…GPER, a G-protein-coupled estrogen receptor that has been demonstrated to mediate rapid estrogen signaling [11], has been shown to be of relevance in a range of cancer types deriving from reproductive [12][13][14][15], as well as non-reproductive [16,17] tissue. However, though GPER has been intensively studied in EOC, to the best of our knowledge, no report exists on GPER in ovarian granulosa cell tumors, so far.…”

A histomorphologic predictive model for axillary lymph node metastasis in preoperative breast cancer core needle biopsy according to intrinsic subtypes

“…Immunohistochemical expression of HER2 was assessed based on 2013 ASCO/CAP guidelines [16]. p53 and bcl-2 expressions were regarded as positive if greater than or equal to 25% of the tumor cells showed nuclear staining [17]. CK5/6 and EGFR (HER1) were scored positive when more than 10% of cytoplasmic staining was observed in the tumor cells [18,19].…”