scholarly journals The low prevalence of colonic serrated adenocarcinoma with high KRAS mutational status at Cipto Mangunkusumo Hospital, Indonesia

2018 ◽  
Vol 27 (3) ◽  
pp. 161-8
Author(s):  
Nur Rahadiani ◽  
Diah R. Handjari ◽  
Marini Stephanie ◽  
Ening Krisnuhoni

Background: Serrated adenocarcinoma (SA), a subtype of colorectal carcinoma, and the KRAS mutation, a strong marker for the patient’s response to anti-epidermal growth factor receptor therapy, have a clinical importance because of its progressive nature and tendency for chemoresistance. The purposes of this study were to (1) determine the prevalence of SA, (2) evaluate the histomorphological characteristics of SA and classical adenocarcinoma based on its prognostic factors, (3) determine the prevalence of the KRAS mutation in SA cases, and (4) identify the main characteristics of SA cases and classical adenocarcinoma with a KRAS mutation.Methods: This study was conducted by reviewing hematoxylin-eosin-stained slides of colorectal carcinoma (CRC) cases from January 2013 to July 2015 at the Department of Anatomical Pathology Cipto Mangunkusumo General Hospital. The final diagnosis of SA was based on the Tuppurainen et al criteria and the KRAS mutation was evaluated using real-time polymerase chain reaction.Results: Among the 117 adenocarcinoma cases, there were 41 unequivocal SA, 11 equivocal SA, and 65 classical adenocarcinoma. The prevalence rates of unequivocal and equivocal SA among all CRC cases were 7.7% and 2.1%, respectively. There were 11 (28.2%) cases of wild-type KRAS and 28 (71.7%) cases of mutated KRAS among all unequivocal SA cases. Tumor budding (TB) was the predominant prognostic factor.Conclusion: The prevalence of SA among all CRC cases was 7.7%. The KRAS mutation was found in almost three-quarters of all SA cases.

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4021-4021
Author(s):  
F. Loupakis ◽  
C. Cremolini ◽  
G. Perrone ◽  
I. Stasi ◽  
L. Salvatore ◽  
...  

4021 Background: AR is an endogenous ligand of Epidermal Growth Factor Receptor (EGFR), whose binding is prevented in the presence of cetuximab. Methods: We retrospectively assessed KRAS mutational status and AR expression at immunohistochemistry (IHC) in 86 irinotecan-refractory EGFR-positive mCRC patients treated with cetuximab plus irinotecan. AR-IHC was performed on tissue sections from paraffin-embedded primary tumors. Specimens were defined AR-low or AR-high according to a score (range 0–300) obtained multiplying intensity (0 to 3+) by percentage of stained cells (0–100%). According to the results of a ROC analysis, we identified a cut-off value of 18. The association between AR-IHC and treatment outcome in terms of response rate (RR), PFS, and OS was investigated in the subgroup of KRAS wild-type patients. Results: Eighty-six consecutive patients were included. M/F = 44/42, median age = 67 (41–78), median number of previous lines of chemotherapy = 2 (1–5). Among 51 (59%) KRAS wild-type patients, 12 PRs and 1 CR were observed, for an overall RR of 25% (13/51). AR-IHC was high, low or unconclusive in 27, 22 and 2 cases respectively. AR-low patients reported a significantly worse RR (2/22, 9%) compared with AR-high (10/27, 37%) (p = 0.024) and a trend toward shorter PFS (3.5 vs 5.3 months, HR 0.88 [95%CI: 0.46–1.60], p = 0.628) and OS (8.8 vs 15.1 months, HR 0.60 [95%CI: 0.30–1.10], p = 0.106). Conclusions: These results underline the potential role of endogenous ligands in influencing the activity of anti-EGFR monoclonal antibodies. Absent or low AR expression at IHC may be related to resistance to cetuximab plus irinotecan. Further data regarding the prognostic impact of AR expression are needed. No significant financial relationships to disclose.


2015 ◽  
Vol 9 (1) ◽  
Author(s):  
Chinachote Teerapakpinyo ◽  
Phanni Wanthong ◽  
Mathawee Aumchaaumchaya ◽  
Piyamai Chankate ◽  
Warisa Kaikeaw ◽  
...  

AbstractBackground, coding for a small G-protein downstream of epidermal growth factor receptor (EGFR) plays an important role in the EGFR signaling network. Mutation inObjectivesTo develop an in-house pyrosequencing method to screen forMaterials and MethodsDNA extracted from FFPE specimens was screened forResultsOf the 74 samples with undetectable codon 12/13 mutation examined, two (2.7%) were found to harbor mutation in codon 61.ConclusionDespite the low prevalence of


2005 ◽  
Vol 11 (4) ◽  
pp. 1368-1371 ◽  
Author(s):  
Hisashi Nagahara ◽  
Koshi Mimori ◽  
Mitsuhiko Ohta ◽  
Tohru Utsunomiya ◽  
Hiroshi Inoue ◽  
...  

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