title: Organic cation transporter 2 and tumor budding as independent prognostic factors in metastatic colorectal cancer patients treated with oxaliplatin-based chemotherapy.
abstract: Oxaliplatin is currently approved for patients with metastatic colorectal cancer (mCRC). Its uptake and consequent cytotoxicity is determined by the levels of organic cation transporter 2 (OCT2). In addition, tumor budding (TB) is associated with high malignant potential. However, the impact of the levels of OCT2 and TB on clinicopathological findings and the prognosis of mCRC patients treated with oxaliplatin-based chemotherapy remains unclear. Here, 80 mCRC patients were retrospectively assessed. Immunohistochemistry was performed to determine the levels of OCT2 and TB. High levels of OCT2 (47/80, 59%) were detected at the invasion front and were associated with depth of invasion (P=0.03), whereas high levels of TB (40/80, 50%) were associated with extensive lymphatic invasion (P=0.03). In univariate analysis, high OCT2 levels were significantly correlated with longer progression-free survival (PFS) (P=0.02) whereas high TB levels were associated with shorter PFS (P=0.01). In combined analysis, patients with 2 favorable factors (high OCT2/low TB) had longer PFS than those with 1 (P=0.03) or 0 (P<0.001) favorable factors. Multivariate analysis confirmed that the OCT2 level (P=0.007), TB level (P=0.004), and combined OCT2/TB status (P=0.001) were independent predictors for PFS. These results suggest that high levels of OCT2 indicate severe invasion, but also better prognosis in mCRC patients treated with oxaliplatin-based chemotherapy, possibly because of its role in oxaliplatin susceptibility. Combined analysis of OCT2 and TB status may guide the selection of patients for successful oxaliplatin-based chemotherapy.
authors.affiliation: Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences 7-10-2 Tomogaoka, Suma, Kobe, Hyogo 654-0142, Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Tatsumi
authors.affiliation: Departments of Surgery, Fujita Health University School of Medicine 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuoka
authors.affiliation: Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences 7-10-2 Tomogaoka, Suma, Kobe, Hyogo 654-0142, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Departments of Surgery, Fujita Health University School of Medicine 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Hatta
authors.affiliation: Departments of Surgery, Fujita Health University School of Medicine 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences 7-10-2 Tomogaoka, Suma, Kobe, Hyogo 654-0142, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kamoshida
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D050813:Octamer Transcription Factor-2 / Q000032:analysis / Q000096:biosynthesis*; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D050813:Octamer Transcription Factor-2; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin
keywords: Organic cation transporter 2; colorectal cancer; oxaliplatin; progression-free survival; tumor budding