Oktay Halit Aktepe1, Taha Koray Sahin2, Gurkan Guner1, Deniz Can Guven1, Haci Hasan Yeter3, Olcay Kurtulan4, Ibrahim Hanifi Ozercan5, Omer Dizdar6, Suayib Yalcin1. 1. Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey. 2. Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey. 3. Department of Nephrology, Gazi University Faculty of Medicine, Ankara, Turkey. 4. Department of Pathology, Hacettepe University Faculty of Medicine, Ankara, Turkey. 5. Department of Pathology, Firat University Faculty of Medicine, Elazığ, Turkey. 6. Department of Preventive Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.
Abstract
BACKGROUND: Thrombospondin type 1 domain-containing 7A (THSD7A) has emerged as a new potential molecular tool for multiple tumors since that THSD7A was detected to be expressed in various malignant tumor types including colorectal cancer (CRC). Thus, we investigated the correlation between THSD7A expression and pathologic determinants of azoxymethane (AOM)-induced CRC in a rat model. METHODS: A total of 30 rats were included in the study (experimental group; n = 15, control group; n = 15). Azoxymethane was administered to the experimental group weekly as subcutaneous injections at a dose of 15 mg/kg bodyweight for 3 weeks. Five months later, 42 tumors were obtained in the study group and histopathologic evaluation of CRC tumors for THSD7A was performed by immunohistochemical staining. Thrombospondin type 1 domain-containing 7A expression was classified according to staining levels. RESULTS: While 28.6% of the colonic tumors were stained as negative, mild-moderate and strong staining was determined in 61.9% and 9.5% of the tumors, respectively. Thrombospondin type 1 domain-containing 7A expression levels inversely correlated with Ki-67 expression (P < .001) and tumor grade (P =.02). Receiver operating characteristic analysis showed Ki-67 staining ≥20.5% was determined as a cut-off value for negatively stained THSD7A tumors with 91% sensitivity and 69% specificity (P = .001, area under curve: 0.822). Moreover, higher Ki-67 expression was found to be associated with higher tumor grade (P < .001), presence of lymphatic invasion (P = .003), and higher T stage (P = .003). CONCLUSION: Negative staining for THSD7A seems to be linked to invasive pathologic determinants in AOM-induced CRC in rats.
BACKGROUND: Thrombospondin type 1 domain-containing 7A (THSD7A) has emerged as a new potential molecular tool for multiple tumors since that THSD7A was detected to be expressed in various malignant tumor types including colorectal cancer (CRC). Thus, we investigated the correlation between THSD7A expression and pathologic determinants of azoxymethane (AOM)-induced CRC in a rat model. METHODS: A total of 30 rats were included in the study (experimental group; n = 15, control group; n = 15). Azoxymethane was administered to the experimental group weekly as subcutaneous injections at a dose of 15 mg/kg bodyweight for 3 weeks. Five months later, 42 tumors were obtained in the study group and histopathologic evaluation of CRC tumors for THSD7A was performed by immunohistochemical staining. Thrombospondin type 1 domain-containing 7A expression was classified according to staining levels. RESULTS: While 28.6% of the colonic tumors were stained as negative, mild-moderate and strong staining was determined in 61.9% and 9.5% of the tumors, respectively. Thrombospondin type 1 domain-containing 7A expression levels inversely correlated with Ki-67 expression (P < .001) and tumor grade (P =.02). Receiver operating characteristic analysis showed Ki-67 staining ≥20.5% was determined as a cut-off value for negatively stained THSD7A tumors with 91% sensitivity and 69% specificity (P = .001, area under curve: 0.822). Moreover, higher Ki-67 expression was found to be associated with higher tumor grade (P < .001), presence of lymphatic invasion (P = .003), and higher T stage (P = .003). CONCLUSION: Negative staining for THSD7A seems to be linked to invasive pathologic determinants in AOM-induced CRC in rats.
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