Department of Surgery, Philipps University Marburg, Marburg, Germany.
Neoplasia. 2011 Feb;13(2):180-6. doi: 10.1593/neo.10956.
Pancreatic cancer is among the most dismal of human malignancies. The 5-year survival rate is lower than 5%. The identification of precursor lesions would be the main step to improve this fatal outcome. One precursor lesions are called pancreatic intraepithelial neoplasia (PanIN) and are graduated in grade 1 to 3, whereas grade 3 is classified as carcinoma in situ. Currently, no reliable, noninvasive imaging technique (e.g., ultrasound, computed tomography, magnet resonance imaging) exists to verify PanINs.
Recently, a transgenic mouse model of pancreatic cancer was established in which the tumor progression of human pancreatic carcinoma is reproduced. These so-called Pdx-1-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+mice develop PanINs, which transform to invasive growing pancreatic carcinoma. The pancreata of mice of different ages were immunohistochemically stained using α-GLUT-2 antibodies. Furthermore, mice underwent positron emission tomography (PET)-computed tomography (CT) with (18)F-fluorodeoxyglucose (FDG) to evaluate early detection of PanIN lesions.
An expression of GLUT-2 in murine PanINs was found in PanINs of grade 1B and higher. This finding is associated with an elevated glucose metabolism, leading to the detection of precursor lesions of pancreatic cancer in the FDG PET-CT scan. In addition, immunohistochemical staining of GLUT-2 was detectable in 45 (75%) of 60 human PanINs, whereas PanINs of grade 1B and higher showed a very extensive expression.
In conclusion, we demonstrate for the first time that an elevated glucose metabolism occurs already in precursor lesions of murine and human pancreatic carcinoma. These findings are the basis for the detection of precursor lesions by PET-CT, thereby helping improving the prognosis of this devastating disease.
胰腺癌是人类恶性肿瘤中最悲惨的疾病之一。 5 年生存率低于 5%。鉴定前体病变将是改善这种致命结局的主要步骤。一种前体病变称为胰腺上皮内瘤变（PanIN），分为 1 级到 3 级，而 3 级被归类为原位癌。目前，尚无可靠的非侵入性成像技术（例如超声，计算机断层扫描，磁共振成像）来验证 PanIN。
最近，建立了一种胰腺癌的转基因小鼠模型，其中重现了人类胰腺癌的肿瘤进展。这些所谓的 Pdx-1-Cre; LSL-KrasG12D / +; LSL-Trp53R172H / +小鼠发展为 PanIN，其转化为侵袭性生长的胰腺癌。使用α-GLUT-2 抗体对不同年龄的小鼠的胰腺进行免疫组织化学染色。此外，对小鼠进行正电子发射断层扫描（PET）-计算机断层扫描（CT）与（18）F-氟脱氧葡萄糖（FDG），以评估 PanIN 病变的早期检测。
在 1B 级及以上的 PanIN 中发现了 GLUT-2 在小鼠 PanIN 中的表达。这一发现与葡萄糖代谢的升高有关，导致在 FDG PET-CT 扫描中检测到胰腺癌的前体病变。此外，在 60 个人类 PanIN 中，45 个（75％）可检测到 GLUT-2 的免疫组织化学染色，而 1B 级及以上的 PanIN 显示出非常广泛的表达。
总之，我们首次证明葡萄糖代谢在小鼠和人类胰腺癌的前体病变中已经升高。这些发现是通过 PET-CT 检测前体病变的基础，从而有助于改善这种毁灭性疾病的预后。
