Immunohistochemistry-based molecular subtyping of triple-negative breast cancer and its prognostic significance

Abstract

Background: Immunohistochemistry (IHC)-based protein markers representing molecular subtypes are of great value for routine use. This study aimed to evaluate the frequency distributions of the molecular subtypes of triple-negative breast cancer (TNBC) using IHC-based surrogate markers and examined their prognostic value.Methods: Patients with TNBC treated at a university hospital in Southern Thailand were included in this study. Expression levels of androgen receptor, CD8, Forkhead box transcription factor C1, and Doublecortin-like kinase 1 were detected in tumor tissue to classify them into luminal androgen receptor (LAR), immunomodulatory (IM), basal-like immunosuppressed (BLIS), mesenchymal-like (MES), and unclassifiable (UC) subtypes. The association between variables and disease-free survival (DFS) and overall survival (OS) was analyzed using Cox proportional hazards regression.Results: Among the 195 cases of TNBC, the frequency distribution of the IHC-based subtype was as follows: BLIS, 52.8%; LAR, 19.0%; IM, 17.4%; MES, 0.5%; and un-classifiable, 10.3%. BLIS subtype was significantly found in younger ages (mean: 49.6 years) than other subtypes (mean: 51–57.7 years). LAR and BLIS subtypes were significantly associated with poorer OS compared to the IM subtype in univariate analysis, however, only BLIS was significant in multivariate analysis (HR: 3.29, 95% CI: 1.01–10.72). IHC-based subtype was not found to be associated with DFS.Conclusion: This study revealed the differences in the proportion frequency of IHC-based TNBC subtypes in Thai patients compared to other populations. IHC-based molecular subtyping may be beneficial for prognosis. However further refinement of the molecular classification of TNBC is needed for better clinical relevance.

Triple-Negative Breast Cancer Subclassified by Immunohistochemistry: Correlation with Clinical and Pathological Outcomes in Patients Receiving Neoadjuvant Chemotherapy

“…In a study conducted by Yoo in 2022, the majority of patients with IHC-unclassifiable had presented with mesenchymal subtype on genomic classification [ 15 ]. Interestingly, Zhao et al, Leeha et al, and Hu et al did not report mixed subtypes by using their IHC panels [ 14 , 17 , 18 ]. We believe IHC-unclassifiable and IHC-mixed should be expected given the IHC assay limitations, and support the heterogeneous features of a significant proportion of TNBCs [ 28 ].…”

“…Immunohistochemistry (IHC) is an established laboratory method for evaluating the presence of antigens that is widely used in breast cancer and is pivotal for tailoring systemic treatments (e.g., the human epidermal growth factor receptor 2—HER2) [ 10 ]. Moreover, IHC is significantly less expensive and laborious than gene expression and has been evaluated in several studies as a surrogate marker of established intrinsic genomic-based subtyping assays, as summarized in Table 1 [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Although some studies have provided survival data amongst the subtypes, the effect of chemotherapy on the pathological complete response, and if it serves as surrogate biomarker of survival, has not been reported.…”

IDO-1 impairs antitumor immunity of natural killer cells in triple-negative breast cancer via up-regulation of HLA-G

“…Cancer tissue and paired para-cancerous tissue of 93 TNBC patients from 2017 to 2018 were collected by the department of oncology of the Second Affiliated Hospital of Xi’an Jiaotong University to investigate the expression of IDO-1 in TNBC patients. The diagnosis of TNBC was histologically confirmed in 93 patients who were at least 18 years old as described previously [ 16 ]. The inclusion requirements included a minimum 3 month survival rate, adequate bone marrow, hepatic, and renal function, and signed informed permission.…”

Imuno-histoquímica no Diagnóstico de Câncer de Mama: Principais Marcadores Proteicos

“…reidratada com álcool em concentrações crescentes, garantindo a preservação da amostra ao ser colocada na lâmina. Posteriormente, é realizada uma lavagem com uma solução salina, seguida pela aplicação dos antígenos marcados para efetuar a marcação da proteína, caso esteja presente na amostra (Leeha et al, 2023).…”