Prognostic values of L-type amino acid transporter 1 and CD98hc expression in breast cancer

Abstract

Aims: L-type amino acid transporter 1 (LAT1) is a major Na⁺-independent neutral amino acid transporter, forming a complex with CD98hc. The aim of this study is to investigate the significance of LAT1 and CD98hc in invasive breast cancer.

Methods: LAT1 and CD98hc expression was immunohistochemically assessed in 280 invasive breast cancers and analysed for association with clinicopathological features.

Results: High levels of LAT1 and CD98hc were observed in triple-negative breast cancers (TNBCs) possessing negative immunoreactivity with oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, compared with non-TNBCs (NTNBCs), and were associated with lymph-node metastasis and higher nuclear grade. The high-LAT1-expression group showed a poor prognosis in NTNBC and TNBC, however, high-CD98hc-expression group showed a poor prognosis only in NTNBC. LAT1 and CD98hc expression could be the prognostic factors in univariate analyses, but not in multivariate analyses. Further, we found that invasive tumour components showed higher LAT1 and CD98hc expression than non-invasive tumour components.

Conclusions: LAT1 and CD98hc may possess prognostic values in invasive breast cancer. LAT1 may be linked with cancer cell activities and disease progression in breast cancer.

Keywords: breast cancer; breast pathology; histopathology.

Figure 1

Representative immunoreactivity of L-type amino acid transporter 1 (A–E) and CD98hc (F–J) in breast cancer tissues. Based on the immunointensity of the carcinoma cell membranes, four categories were defined. intensity 0, no immunoreactivity (A and F); intensity 1, weakly positive (B and G); intensity 2, moderately positive (C and H); intensity 3, strong expression (D and I). Normal epithelia with negative staining (E, J). Original magnifications ×400.

Figure 2

Association of LAT1 and CD98hc expression with clinicopathological parameters. (A–D) Analyses of LAT1 expression in all cases. (E and F) Analyses of LAT1 expression in NTNBC cases. (G–J) Analyses of CD98 expression in all cases. (K and L) Analyses of CD98hc expression in NTNBC cases. Number of cases in each group is indicated in parentheses. *P value <0.05. LAT1, L-type amino acid transporter 1; LN(+), with lymph node metastasis; LN(−), without lymph node metastasis; NG, nuclear grade; NTNBC, non-triple-negative breast cancer; TNBC, triple-negative breast cancer.

Figure 3

L-type amino acid transporter 1 (LAT1) and CD98hc expression is upregulated in invasive lesions compared with non-invasive lesions. A representative area for both invasive and non-invasive lesions is shown. (A) H&E staining. (B) Immunohistochemical staining for LAT1. (C) Immunohistochemical staining for CD98hc. The right lower part indicates invasive lesions (I), whereas the left upper part indicates non-invasive lesions (N–I). Original magnifications ×100.

Figure 4

Overall survival curves in association with LAT1 and CD98hc expression. Cases were divided into high-expression and low-expression groups according to LAT1 and CD98hc scores (0–4 as low and 6–9 as high). Kaplan-Meier curves of the groups in all cases (A, E, I), in NTNBC cases (B, F, J), in TNBC (C, G, K) and incases with pathological stage II and III (D, H, L) are shown. LAT1, L-type amino acid transporter 1; NTNBC, non-triple-negative breast cancer; TNBC, triple-negative breast cancer.