Decreased expression of folate transport proteins in oral cancer

• Published in: Oral surgery, oral medicine, oral pathology and oral radiology Vol. 127; no. 5; pp. 417 - 424
• Main Authors: Goral, Joanna, Cuadros, Kayla, Pitstick, Lenore, Meyer, Alice, Jham, Bruno Correia, Guimaraes, Eduardo Pereira, Hanemann, João Adolfo Costa, Green, Jacalyn M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2019
• Subjects: Carcinoma, Squamous Cell; Dentistry; Folic Acid; Folic Acid Antagonists; Folic Acid Transporters; Humans; Mouth Neoplasms; Reduced Folate Carrier Protein
• ISSN: 2212-4403; 2212-4411
• DOI: 10.1016/j.oooo.2018.09.005

The purpose of this study was to assess the expression of the 3 major folate transporters—folate receptors (FRs), reduced folate carrier (RFC), and proton-coupled folate transporter (PCFT)—in oral squamous cell carcinoma (OSCC). We hypothesized that patterns of expression of folate transporters would be different in OSCC compared with normal oral epithelium. We used immunohistochemistry to examine the expression of FR, RFC, and PCFT in 15 primary specimens collected from patients with OSCC, 2 human cadaveric samples of OSCC, and 12 normal human cadaveric oral tissues from a medical gross anatomy laboratory. Possible correlations between the expression of each folate transporter and patients’ clinical data were determined. All 3 folate transporters were highly expressed in normal oral epithelium. In contrast, OSCC samples generally demonstrated low expression of FR, RFC, and PCFT, with wide distribution in the invading cancer cells. There were no differences in folate transporter expression between OSCC samples collected from patients and from human cadavers. The lowest expression of FR and PCFT characterized less-differentiated tumors, and the lowest expression of RFC correlated with higher lymph node involvement. Human oral cancer samples expressed decreased amounts of all 3 major folate transport proteins compared with controls from normal cadaveric oral tissues.