Oltedal Satu, Kørner Hartwig, Aasprong Ole Gunnar, Hussain Israr, Tjensvoll Kjersti, Smaaland Rune, Søreide Jon Arne, Søreide Kjetil, Lothe Ragnhild A, Heikkilä Reino, Gilje Bjørnar, Nordgård Oddmund
Department of Hematology and Oncology, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway.
Department of Gastrointestinal Surgery, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway; Department of Clinical Medicine, University of Bergen, Jonas Lies veg 87, 5021 Bergen, Norway.
Transl Oncol. 2018 Apr;11(2):436-443. doi: 10.1016/j.tranon.2018.01.015. Epub 2018 Feb 21.
Regional lymph node (LN) metastasis is a strong and well-established prognostic factor in colon cancer, and recent data suggest a prognostic value of detecting micrometastases and isolated tumor cells in regional LNs. The aim of the study was to investigate the clinical relevance of detecting sentinel lymph node (SLN) metastases in colon cancer patients by measuring the novel metastasis marker PHGR1 mRNA.
Using quantitative reverse-transcription polymerase chain reaction, we measured PHGR1 mRNA levels in SLNs and primary tumors from 206 patients surgically treated for stage I to III colon cancer and 52 normal LNs from patients undergoing surgery for benign colon diseases. The prognostic impact of these findings was evaluated by Kaplan-Meier analysis and Cox proportional-hazards regression.
Compared to normal LNs, elevated PHGR1 mRNA levels were detected in SLNs from 56 (89%) of the 63 patients with pN+ disease. Furthermore, 68 (48%) of the 143 node-negative (pN0) patients had elevated PHGR1 mRNA levels in SLNs, suggesting occult metastases. With a median follow-up of 7.2 years, a significantly shorter recurrence-free (P=.005) and disease-specific (P=.02) survival was observed in patients with elevated PHGR1 mRNA levels in SLNs. Multivariable modeling showed that the SLN PHGR1 mRNA level was an independent prognostic factor. However, when the survival analyses were restricted to pN0 patients, no significant prognostic information was found.
Measuring PHGR1 mRNA in SLNs provided independent prognostic information on operable colon cancer patients but not in the pN0 subgroup.
区域淋巴结(LN)转移是结肠癌中一个强大且已确立的预后因素,最近的数据表明检测区域淋巴结中的微转移和孤立肿瘤细胞具有预后价值。本研究的目的是通过测量新型转移标志物PHGR1 mRNA来研究检测结肠癌患者前哨淋巴结(SLN)转移的临床相关性。
我们使用定量逆转录聚合酶链反应,测量了206例接受I至III期结肠癌手术治疗患者的SLN和原发肿瘤中的PHGR1 mRNA水平,以及52例接受良性结肠疾病手术患者的正常淋巴结中的PHGR1 mRNA水平。通过Kaplan-Meier分析和Cox比例风险回归评估这些发现的预后影响。
与正常淋巴结相比,63例pN+疾病患者中有56例(89%)的SLN中检测到PHGR1 mRNA水平升高。此外,143例淋巴结阴性(pN0)患者中有68例(48%)的SLN中PHGR1 mRNA水平升高,提示隐匿性转移。中位随访7.2年,SLN中PHGR1 mRNA水平升高的患者无复发生存期(P = 0.005)和疾病特异性生存期(P = 0.02)明显缩短。多变量建模显示SLN PHGR1 mRNA水平是一个独立的预后因素。然而,当生存分析仅限于pN0患者时,未发现显著的预后信息。
测量SLN中的PHGR1 mRNA可为可手术的结肠癌患者提供独立的预后信息,但在pN0亚组中则不然。