Pelli Ari, Väyrynen Juha P, Klintrup Kai, Mäkelä Jyrki, Mäkinen Markus J, Tuomisto Anne, Karttunen Tuomo J
Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.
Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland.
Histopathology. 2016 Nov;69(5):831-838. doi: 10.1111/his.13006. Epub 2016 Aug 2.
Gremlin1 is a bone morphogenetic protein (BMP) antagonist with a suggested role in colorectal cancer (CRC) progression. We have analysed Gremlin1 protein expression in CRC and assessed its correlation with clinicopathological characteristics, including developmental pathway and prognosis.
Material included a non-selected series of 148 surgically treated CRC cases. The tumour-node-metastasis (TNM) stage, histological grade and inflammatory infiltrate at the invasive margin were assessed, and tumours were classified to serrated or non-serrated types. Immunohistochemistry was conducted to evaluate Gremlin1 expression. Prognosis (60-month follow-up) was analysed by Kaplan-Meier methods and Cox regression analysis. Gremlin1 expression was detected in epithelial cells both in normal mucosa and in carcinomas. Abundant expression in carcinomas associated with low TNM stage (P = 0.044), low histological grade (P = 0.044), serrated histology (P = 0.033 or P = 0.053 depending on the classification cut-off) and intensive inflammatory infiltrate at the invasive margin (P = 0.044), and was a stage independent indicator of extended survival (P = 0.029).
Gremlin1 protein expression in CRC associates with low tumour stage and extended survival independently of tumour stage, suggesting that it represents a relevant prognostic indicator in CRC. High expression in carcinomas with serrated histology suggests a potential role for Gremlin1 in the serrated pathway of CRC.
Gremlin1是一种骨形态发生蛋白（BMP）拮抗剂，在结直肠癌（CRC）进展中可能发挥作用。我们分析了CRC中Gremlin1蛋白的表达，并评估了其与临床病理特征（包括发育途径和预后）的相关性。
材料包括148例接受手术治疗的CRC非选择性病例系列。评估肿瘤-淋巴结-转移（TNM）分期、组织学分级和浸润边缘的炎症浸润情况，并将肿瘤分为锯齿状或非锯齿状类型。采用免疫组织化学法评估Gremlin1的表达。通过Kaplan-Meier法和Cox回归分析对预后（60个月随访）进行分析。在正常黏膜和癌组织的上皮细胞中均检测到Gremlin1表达。癌组织中高表达与低TNM分期（P = 0.044）、低组织学分级（P = 0.044）、锯齿状组织学（根据分类临界值，P = 0.033或P = 0.053）以及浸润边缘的强烈炎症浸润（P = 0.044）相关，并且是延长生存期的独立分期指标（P = 0.029）。
CRC中Gremlin1蛋白表达与低肿瘤分期及独立于肿瘤分期的延长生存期相关，提示它是CRC中一个相关的预后指标。在具有锯齿状组织学的癌组织中高表达提示Gremlin1在CRC的锯齿状途径中可能发挥作用。
