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Upregulation of glucose and amino acid transporters in micropapillary carcinoma

Kanae Nosaka, Karen Makishima, Tomohiko Sakabe, Yohei Yurugi, Makoto Wakahara, Yasuaki Kubouchi, Yasushi Horie, Yoshihisa Umekita
Histology and Histopathology 2019 March 11, : 18099
Micropapillary carcinoma (MPC), a relatively rare histologic carcinoma observed in various organs, is associated with vascular invasion, nodal metastasis, and poor prognosis. MPC is different from papillary carcinoma as it has no fibrovascular core and is thus considered essentially hypovascular. MPCs are known to upregulate glucose transporter 1 (GLUT1) via the activation of a transcription factor, hypoxia-inducible factor (HIF)-1. Here we evaluated the expression of nutrient transporters in MPCs to gain a better understanding of the system used by MPCs to compensate for their intrinsic poor vascularity. We immunohistochemically evaluated 29 MPCs including breast (n=14), lung (n=8), gastrointestinal tract (n=5), and urinary tract cancers (n=2) and compared them with non-micropapillary control cancers (n=32) regarding the expression of amino acid (ASCT1, ASCT2, LAT1, and SNAT1) and glucose (GLUT1, GLUT2) transporters. Each section was scored by the staining intensity (0-3) multiplied by the occupying area (0-10), with a possible range 0-30. The average scores of the MPC and control groups were compared by Student's or Welch's t-test according to the homoscedasticity. The MPC group showed markedly and significantly higher scores for ASCT1 (p=0.007), ASCT2 (p=0.001), GLUT1 (p<0.001), and GLUT2 (p<0.001), whereas no significant between-group difference was observed in the LAT1 and SNAT1 scores. In conclusion, MPC could be associated with the upregulation of several nutrient transporters, which may contribute to the malignant potential by supporting the survival of cancer cells.


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