Cancer Res Treat.  2017 Jan;49(1):185-192. 10.4143/crt.2015.497.

Rare Incidence of ROS1 Rearrangement in Cholangiocarcinoma

• Lim SM
• Yoo JE
• Lim KH
• Meng Tai D
• Cho BC
• Park YN

• KMID: 2367516
• DOI: http://doi.org/10.4143/crt.2015.497

Abstract

PURPOSE
The recent discovery and characterization of an oncogenic ROS1 gene rearrangement has raised significant interest because small molecule inhibitors are effective in these tumors. The aim of this study was to determine frequency and clinicopathological features associated with ROS1 rearrangement in patients with cholangiocarcinoma (CCA).
MATERIALS AND METHODS
A total of 261 patients who underwent surgery for CCA between October 1997 and August 2013 were identified from an international, multi-institutional database. ROS1 rearrangement was evaluated by break-apart fluorescence in situ hybridization using tissue microarrays of these patients.
RESULTS
Of 261 CCA evaluated, three cases (1.1%) showed ROS1 rearrangement by fluorescence in situ hybridization (FISH), all of which were derived from intrahepatic origin. ROS1 protein expression was observed in 38 samples (19.1%). Significantly larger tumor size was observed in ROS1 immunohistochemistry (IHC)-negative patients compared with ROS1 IHC-positive patients. ROS1 FISH-positive patients had a single tumor with a median size of 4 cm and well-to-moderate differentiation. Overall, there was no difference in terms of baseline characteristics, overall survival, and recurrence-free survival between ROS1-positive and -negative patients.
CONCLUSION
ROS1 rearrangement was detected in 1.1% of CCA patients. Although rare, conduct of clinical trials using ROS1 inhibitors in these genetically unique patients is warranted.

Keyword

Cholangiocarcinoma; ROS1; Fluorescent in situ hybridization

MeSH Terms

Cholangiocarcinoma*
Fluorescence
Gene Rearrangement
Humans
Immunohistochemistry
In Situ Hybridization
In Situ Hybridization, Fluorescence
Incidence*

Figure

• 

  Fig. 1. Representative ROS1 rearrangement features in cholangiocarcimomas. Fluorescence in situ hybridization (FISH) showing ROS1 rearrangement with break-apart signals in patients 1 and 2 and single green signals in patient 3. FISH showing ROS1 rearrangement with break-apart signals in low-power field (A, F, K) and high-power field (B, G, L). FISH showing ROS1 rearrangement with single green signals (K, L). The arrows indicate ROS1 break-apart or single green signals (A, F, K, ×400; B, G, L, ×630). Immunohistochemical stain for ROS1 in ROS1 rearranged cholangiocarcinoma (C, H, M, ×200). Microscopic features (D, I, N, H&E staining, ×200) and photographs of surgical specimens (E, J, O) are also shown.

• 

  Fig. 2. Survival analysis. (A) Kaplan-Meier curve of median overall survival (OS) of all patients. (B) Kaplan-Meier curve of median recurrence-free survival (RFS) of all patients. (C) Comparison of OS between ROS1-positive and -negative patients. (D) Comparison of RFS between ROS1-positive and -negative patients. CI, confidence interval.

Reference

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