PATIENT-DERIVED ORTHOTOPIC GRAFT MODEL OF ORAL CANCER: HISTOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL COMPARISON.

Abstract

Objective Patient-derived xenograft (PDX) model seems to recapitulate the histopathology of the original donor tumor. Here we compared the histopathological characteristics of the donor tumor with sequential implantations of tumor fragments derived from a human tongue squamous cell carcinoma biopsy in the PDX model. Study Design We orthotopically transplanted a primary tongue tumor into immunosuppressed mice, which was successively reimplanted over 6 passages (P0, P1, P2, P3, P4, and P5). Histopathological characteristics were evaluated by hematoxylin and eosin staining and pan-cytokeratin; Ki-67, and HIF-1α were evaluated by immunohistochemistry. Results Tumor size was smaller in later passages (P4 and P5). P0 tumors were classified as well-differentiated, while the other passages were classified as moderately differentiated. Vascular and perineural invasion occurred only in later passages and were not present in the donor patient tissue. Dyskeratosis and keratin pearls were observed in most of the studied passages but not evident in the patient sample. Cell pleomorphism was similar between the studied passages. Ki-67 showed very homogeneous cell proliferation rates between passages and the donor tumor. HIF-1α immunolabeling was absent in the analyzed tumor samples. Conclusion P1 and P2 tumors more accurately reproduce the morphological characteristics of the donor patient's primary tumor. (FAPESP 2019/21513-2) Patient-derived xenograft (PDX) model seems to recapitulate the histopathology of the original donor tumor. Here we compared the histopathological characteristics of the donor tumor with sequential implantations of tumor fragments derived from a human tongue squamous cell carcinoma biopsy in the PDX model. We orthotopically transplanted a primary tongue tumor into immunosuppressed mice, which was successively reimplanted over 6 passages (P0, P1, P2, P3, P4, and P5). Histopathological characteristics were evaluated by hematoxylin and eosin staining and pan-cytokeratin; Ki-67, and HIF-1α were evaluated by immunohistochemistry. Tumor size was smaller in later passages (P4 and P5). P0 tumors were classified as well-differentiated, while the other passages were classified as moderately differentiated. Vascular and perineural invasion occurred only in later passages and were not present in the donor patient tissue. Dyskeratosis and keratin pearls were observed in most of the studied passages but not evident in the patient sample. Cell pleomorphism was similar between the studied passages. Ki-67 showed very homogeneous cell proliferation rates between passages and the donor tumor. HIF-1α immunolabeling was absent in the analyzed tumor samples. P1 and P2 tumors more accurately reproduce the morphological characteristics of the donor patient's primary tumor.