KRAS mutational status of endoscopic biopsies matches resection specimens

Yang, Qinghua; Schmidt, Jörg; Soucy, Genvieve; Odze, Robert D.; Dejesa-Jamanila, Liza; Arnold, Keely; Kuslich, Christine; Lash, Richard H.

doi:10.1136/jclinpath-2012-200746

Cited by 9 publications

(11 citation statements)

References 41 publications

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“…Endoscopic samples may be useful in rectal adenocarcinoma specimens with low tumour cellularity, after neoadjuvant treatment. The reliability of endoscopic biopsy has also been proved by two very recent studies showing that the KRAS mutant rate is highly concordant in matched endoscopic and resection specimens 20 21. However, in our series in 8.0% of biopsies the residual material following standard histology and ancillary techniques was insufficient.…”

Section: Discussionsupporting

confidence: 56%

Sanger sequencing in routine KRAS testing: a review of 1720 cases from a pathologist's perspective

et al. 2012

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BackgroundSanger sequencing (SS) of PCR products is still the most frequent method to test colorectal cancer for KRAS mutations in routine practice.MethodsAn audit of SS on 1720 routine cases was carried out, taking into account age, gender, specimen type (resection vs biopsies), tumour site (primary vs metastasis), tumour stage, neoplastic cells abundance (>30% vs <30%) and fixation type (buffered formalin vs simple formalin). In a subset of 50 wild-type (WT) patients correlations between SS findings and response rate (RR), progression-free survival (PFS) and overall survival (OS) were also evaluated.ResultsThe tests were informative in 1691 cases (98.3%). Mutations were detected in 671 cases (39.6%). No significant differences in mutation rates were observed with respect to age (p=0.2), gender (p=0.2), specimen type (p=0.3) and formalin fixation (p=0.08). Conversely, KRAS mutant rate was higher in metastatic tissue (50% vs 39%, p=0.02), in samples with over 30% of neoplastic cells (43.4% vs 26.6%, p=0.02) and in tumours tested in stage IV (p=0.05). The RR of SS KRAS WT patients was 26% (one complete and 12 partial responses). The disease control rate (objective responses plus stable disease) was 56%. Median PFS was 4.4 months and median OS was 10.4 months.ConclusionsPathological criteria that make SS a more robust method for KRAS testing and treatment response prediction are neoplastic cell abundance, metastatic tissue sample and stage IV primary tumour.

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Section: Discussionsupporting

confidence: 56%

Sanger sequencing in routine KRAS testing: a review of 1720 cases from a pathologist's perspective

et al. 2012

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“…The same KRAS point mutation was identified in the biopsy and in the corresponding resection specimens in 12/12 cases 37. In a larger series (n=125) of paired samples, concordance of KRAS mutational status between biopsy and resection specimens was very high regardless of the method used 38.…”

Section: The Samplementioning

confidence: 76%

KRAS testing in metastatic colorectal carcinoma: challenges, controversies, breakthroughs and beyond

et al. 2013

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Metastatic colorectal cancer harbouring a mutation in codon 12 or 13 of the KRAS gene does not benefit from therapy with antibodies targeting the epidermal growth factor receptor (EGFR). The implementation of community KRAS testing is generating a rapid flow of new data that have implications for the pathologist and testing guidelines besides the physician. Therefore, it seems timely to draw together the threads of this large body of information in order that pathologists can be knowledgeable partners in the multidisciplinary process of targeted cancer therapy and to help refine current testing guidelines. This review addresses (1) the most relevant methodological and technical aspects of KRAS testing in terms of sample site (primary/metastatic), test specimens (resection/biopsy/cytology) and the diverse molecular methods available; (2) the issues related to daily practice, namely, the timing of the test, its turnaround time and the quality control procedures; and (3) the evidence related to the relationship between KRAS genetic intratumoural heterogeneity, clinical sensitivity of mutational detection tools and anti-EGFR treatment outcome. Hopefully, in the near future, elucidation of the potential of biomarker panels and of the mechanisms underlying primary and acquired resistance to anti-EGFR therapy will refine even further personalised treatment regimens for patients with metastatic colorectal cancer.

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“…Eight (11%) studies included details on the size of the biopsies . However, biopsy size reporting varied from being descriptive ‘usually measuring approximately 2–3 mm’ or ‘approximately 2 mm in size’ to measurements of areas; mean area (1 mm 2 ), median and range area (1.92 mm 2 , 0.99–3.37 mm 2 ), diameters (1–5 mm and minimum diameter of 2 mm in greatest dimension), length (mean length (1 mm)) and weight (weight range: 5–80 mg) . Only one study described how the reported measurements were obtained …”

Section: Resultsmentioning

confidence: 99%

Endoscopic biopsies from gastrointestinal carcinomas and their suitability for molecular analysis: a review of the literature and recommendations for clinical practice and research

et al. 2015

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Endoscopic biopsies (EBs) are the gold standard for diagnosing gastrointestinal carcinoma yet no guidelines address EB use for prognostic and predictive molecular testing. This review summarizes the reported quantity and quality of EBs, their relationship with molecular test failure rates and the resultant concordance between EB and resection specimen. Studies reporting molecular testing on gastrointestinal carcinoma EBs published between 2002 and 2014 were identified. Details regarding EB quantity, quality, tumour content, molecular test failure rates as well as causes and concordance with resection specimens were reviewed. Seventy-five studies were identified. Eighteen (24%) reported the mean EB number per patient (median: 2.1, range: 1-6.6 EBs). Sixty-one (81%) reported the frequency of test failure (median: 0%, range: 0-100%). Twenty-two (29%) investigated EB and resection specimen concordance (range: 0-100%). EB quantity and quality affected neither concordance nor failure rate. In summary, few studies currently report EB quantity, EB quality or EB and resection specimen concordance. Reliable molecular testing in EBs appears achievable, and can be representative of resection specimens. Concordance depends upon the testing methodology and biomarker heterogeneity within the tumour. To improve patient care, EB sampling, processing and reporting requires standardization and needs optimization for each biomarker individually.

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KRAS mutational status of endoscopic biopsies matches resection specimens

Abstract: This study shows perfect correlation between KRAS mutation status in biopsy and resection specimens from an individual patient, and suggests that biopsy material is adequate for KRAS mutational analysis in CRC patients.

Cited by 9 publications

References 41 publications

Sanger sequencing in routine KRAS testing: a review of 1720 cases from a pathologist's perspective

Sanger sequencing in routine KRAS testing: a review of 1720 cases from a pathologist's perspective

KRAS testing in metastatic colorectal carcinoma: challenges, controversies, breakthroughs and beyond

Endoscopic biopsies from gastrointestinal carcinomas and their suitability for molecular analysis: a review of the literature and recommendations for clinical practice and research

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