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. 2018 Apr;11(2):436-443.
doi: 10.1016/j.tranon.2018.01.015. Epub 2018 Feb 21.

The Prognostic Relevance of Sentinel Lymph Node Metastases Assessed by PHGR1 mRNA Quantification in Stage I to III Colon Cancer

Satu Oltedal  1 , Hartwig Kørner  2 , Ole Gunnar Aasprong  3 , Israr Hussain  1 , Kjersti Tjensvoll  1 , Rune Smaaland  1 , Jon Arne Søreide  2 , Kjetil Søreide  4 , Ragnhild A Lothe  5 , Reino Heikkilä  6 , Bjørnar Gilje  1 , Oddmund Nordgård  7
Affiliations

The Prognostic Relevance of Sentinel Lymph Node Metastases Assessed by PHGR1 mRNA Quantification in Stage I to III Colon Cancer

Satu Oltedal et al. Transl Oncol. 2018 Apr.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: Measuring PHGR1 mRNA in SLNs provided independent prognostic information on operable colon cancer patients but not in the pN0 subgroup.

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Figures

Figure 1
Figure 1
Flowchart of patient inclusion, SLN mapping, and diagnostics.
Figure 2
Figure 2
Boxplot showing relative PHGR1 mRNA levels in primary colon tumors, normal lymph nodes (LNs), and HES-positive (HES+) and -negative (HES−) SLNs. The horizontal line shows the threshold used to characterize the SLNs as positive or negative for the marker.
Figure 3
Figure 3
Kaplan-Meier survival analyses of recurrence-free and disease-specific survival according to SLN PHGR1 status. (A and C) Recurrence-free survival in all patients (A) and pN0 patients (C). (B and D) Disease-specific survival in all patients (B) and pN0 patients (D).
Supplementary Figure S1
Supplementary Figure S1
Relative PHGR1 mRNA concentrations in dilutions of LS174T cells in 1E7 normal lymphocytes. Error bars indicate standard deviations.
See this image and copyright information in PMC

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