Expression of L‐type amino acid transporter 1 (LAT1) as a prognostic and therapeutic indicator in multiple myeloma

L‐type amino‐acid transporter 1 (LAT1) plays a key role in cell growth and survival. To determine the prognostic significance of LAT1 in multiple myeloma (MM), we investigated the expression of LAT1 and its functional subunit, 4Fc heavy chain (CD98), on myeloma cells by immunohistochemistry in 100 n...

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Published in:Cancer science Vol. 105; no. 11; pp. 1496 - 1502
Main Authors: Isoda, Atsushi, Kaira, Kyoichi, Iwashina, Masanori, Oriuchi, Noboru, Tominaga, Hideyuki, Nagamori, Shushi, Kanai, Yoshikatsu, Oyama, Tetsunari, Asao, Takayuki, Matsumoto, Morio, Sawamura, Morio
Format: Journal Article
Language:English
Published: England John Wiley & Sons, Inc 01-11-2014
Blackwell Publishing Ltd
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Summary:L‐type amino‐acid transporter 1 (LAT1) plays a key role in cell growth and survival. To determine the prognostic significance of LAT1 in multiple myeloma (MM), we investigated the expression of LAT1 and its functional subunit, 4Fc heavy chain (CD98), on myeloma cells by immunohistochemistry in 100 newly diagnosed MM patients. High expression (moderate or strong staining intensity) of LAT1 and CD98 was detected in 56% and 45% of patients, respectively. The LAT1 expression score was positively correlated with Ki‐67 index (r = 0.631, P < 0.001), and there was a statistically significant difference in Durie–Salmon stage between patients with high and low LAT1 expression (P = 0.03). In 43 patients treated with melphalan and prednisolone, the overall response rate was significantly higher in the high LAT1 expression group (60.0%) than in the low LAT1 expression group (17.6%) (P = 0.03). Multivariate analysis confirmed that high expression of LAT1 was a significant prognostic factor for predicting poor overall survival independently from the International Staging System (both P = 0.01). Here, we show that the overexpression of LAT1 is significantly associated with high proliferation and poor prognosis in newly diagnosed MM patients. Thus, LAT1 may be a promising pathological marker for identifying high‐risk MM. L‐[3‐18F]‐α‐methyl tyrosine (18F‐FAMT) is amino acid PET tracer with a high specificity for differentiate between malignant and benign lesions. Metabolic response on 18F‐FAMT PET could correctly reflect the tumor response after systemic chemotherapy by PET Response Criteria in Solid Tumors guideline in patients with advanced lung cancer. Our results suggest that metabolic response on 18F‐FAMT PET has a potential for predicting the outcome after first‐line chemotherapy.
Bibliography:National Institute of Biomedical Innovation, Japan.
Funding Information
Funding Information National Institute of Biomedical Innovation, Japan.
ISSN:1347-9032
1349-7006
DOI:10.1111/cas.12529