Background. The widely used genetically engineered mouse LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre, termed KPC, spontaneously develops pancreatic cancer mirroring all phases of the carcinogenesis but in asynchronous manner. Preclinical studies need defined criteria for the enrollment of the KPC sharing the same stage of carcinogenesis. Aim. To define a tumor-staging criteria using magnetic resonance (MR) and ultrasound (US) and then to correlate the imaging stage with overall survival of KPC mice.Methods. Forty KPC (2- to 5-month-old mice) were imaged by axial fat-saturated T2-weighted sequences at MR and by brightness mode US to establish criteria for tumor staging. Immunohistopathology was used to validate imaging. A second cohort of 25 KPC was used to correlate imaging stage with survival by Kaplan-Meier analysis.Results. We defined a four-class tumor staging system ranking from stages 1 to 4. Stage 1 was described as radiologically healthy pancreas; precursor lesions were detectable in histology only. Cystic papillary neoplasms, besides other premalignant alterations, marked stage 2 in the absence of cancer nodules. Stages 3 and 4 identified mice affected by overt pancreatic cancer with size <5 or ?.5 mm, respectively. Regarding the prognosis, this staging system correlated with disease-related mortality whatever may be the KPC age when they staged.Conclusion. This imaging-based four-class tumor staging is an effective and safe method to stage pancreatic cancer development in KPC. As a result, regardless of their age, KPC mice can be synchronized based on prognosis or on a specific phase of tumorigenesis, such as the early but already radiologically detectable one (stage 2).

Four-class tumor staging for early diagnosis and monitoring of murine pancreatic cancer using magnetic resonance and ultrasound

Liberati, Daniela;De Sanctis, Francesco;Ugel, Stefano;
2018

Abstract

Background. The widely used genetically engineered mouse LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre, termed KPC, spontaneously develops pancreatic cancer mirroring all phases of the carcinogenesis but in asynchronous manner. Preclinical studies need defined criteria for the enrollment of the KPC sharing the same stage of carcinogenesis. Aim. To define a tumor-staging criteria using magnetic resonance (MR) and ultrasound (US) and then to correlate the imaging stage with overall survival of KPC mice.Methods. Forty KPC (2- to 5-month-old mice) were imaged by axial fat-saturated T2-weighted sequences at MR and by brightness mode US to establish criteria for tumor staging. Immunohistopathology was used to validate imaging. A second cohort of 25 KPC was used to correlate imaging stage with survival by Kaplan-Meier analysis.Results. We defined a four-class tumor staging system ranking from stages 1 to 4. Stage 1 was described as radiologically healthy pancreas; precursor lesions were detectable in histology only. Cystic papillary neoplasms, besides other premalignant alterations, marked stage 2 in the absence of cancer nodules. Stages 3 and 4 identified mice affected by overt pancreatic cancer with size <5 or ?.5 mm, respectively. Regarding the prognosis, this staging system correlated with disease-related mortality whatever may be the KPC age when they staged.Conclusion. This imaging-based four-class tumor staging is an effective and safe method to stage pancreatic cancer development in KPC. As a result, regardless of their age, KPC mice can be synchronized based on prognosis or on a specific phase of tumorigenesis, such as the early but already radiologically detectable one (stage 2).
Animals; Disease Models, Animal; Female; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neoplasm Staging; Pancreas; Precancerous Conditions; Ultrasonography; Pancreatic Neoplasms
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1011317
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