Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2015 Apr 15;10(4):e0123759.
doi: 10.1371/journal.pone.0123759. eCollection 2015.

YKL-40/c-Met expression in rectal cancer biopsies predicts tumor regression following neoadjuvant chemoradiotherapy: a multi-institutional study

Affiliations
Multicenter Study

YKL-40/c-Met expression in rectal cancer biopsies predicts tumor regression following neoadjuvant chemoradiotherapy: a multi-institutional study

Rebecca Senetta et al. PLoS One. .

Abstract

Background: Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patients with advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied as putative predictors of CRT response in rectal cancer, due to their reported involvement in chemoradioresistance in various solid tumors.

Material and methods: A multicentric study was designed to assess the role of c-Met and YKL-40 expression in predicting chemoradioresistance and to correlate clinical and pathological features with CRT response. Immunohistochemistry and fluorescent in situ hybridization for c-Met were performed on 81 rectal cancer biopsies from patients with locally advanced rectal adenocarcinoma. All patients underwent standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m2) neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical resection specimens and recorded as tumor regression grade (TRG) according to the Mandard criteria.

Results: A significant correlation between c-Met and YKL-40 expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both significantly associated with a lack of complete response (86% and 87% of c-Met and YKL-40 positive cases, p< 0.01 and p = 0.006, respectively). Thirty of the 32 biopsies co-expressing both markers had partial or absent tumor response (TRG 2-5), strengthening their positive predictive value (94%). The exclusive predictive role of YKL-40 and c-Met was confirmed using a multivariate analysis (p = 0.004 and p = 0.007 for YKL-40 and c-Met, respectively). TRG was the sole morphological parameter associated with poor outcome.

Conclusion: c-Met and YKL-40 expression is a reliable predictor of partial/absent response to neoadjuvant CRT in rectal cancer. Targeted therapy protocols could take advantage of prior evaluations of c-MET and YKL-40 expression levels to increase therapeutic efficacy.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Distribution of patients according to TRG classes.
Fig 2
Fig 2. Representative examples of rectal carcinoma (A, Hematoxylin & Eosin, original magnification 200X) with mild to strong cytoplasmic immunoreactivity for YKL-40 (B, original magnification 400X) and c-Met (C, original magnification 400X) and high c-Met gene polisomy by FISH analysis.
Fig 3
Fig 3. Distribution of cases into to TRG classes according to YKL-40 immunoreactivity (A) and overexpression of YKL-40 in the non-responder group (TRG2-5) when considered both as continuous (B) and categorical variable (C).
Fig 4
Fig 4. Distribution of cases into to TRG classes according to c-Met immunoreactivity (A) and overexpression of c-Met in the non-responder group (TRG2-5) when considered both as continuous (B) and categorical variable (C).
Fig 5
Fig 5. Stratification of cases into three subgroups, according to the expression of YKL-40 and c-Met on tumor biopsy:-/-: YKL-40-negative/c-Met-negative;-/+: YKL-40-positive/c-Met-negative or YKL-40-negative/c-Met-positive and +/+: YKL-40-positive/c-Met-positive.

Similar articles

Cited by

References

    1. Frykholm GJ, Pahlman L, Glimelius B. Combined chemo- and radiotherapy vs. radiotherapy alone in the treatment of primary, nonresectable adenocarcinoma of the rectum. Int J Radiat Oncol Biol Phys. 2001;50: 427–434 - PubMed
    1. Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355: 1114–1123 - PubMed
    1. Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Påhlman L, et al. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol. 2008;26: 3687–3694 10.1200/JCO.2007.15.3858 - DOI - PubMed
    1. Ricardi U, Racca P, Franco P, Munoz F, Fanchini L, Rondi N, et al. Prospective phase II trial of neoadjuvant chemo-radiotherapy with Oxaliplatin and Capecitabine in locally advanced rectal cancer (XELOXART). Med Oncol. 2013;30: 581 10.1007/s12032-013-0581-0 - DOI - PubMed
    1. Janjan NA, Khoo VS, Abbruzzese J, Pazdur R, Dubrow R, Cleary KR, et al. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys. 1999;44: 1027–1038 - PubMed

Publication types

MeSH terms

Grants and funding

RS has received fellowships from FIRC (Fondazione Italiana per la Ricerca sul Cancro). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.