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Published on: March 21, 2018
KRAS mutation analysis on cytological specimens of metastatic colo-rectal cancer
Giancarlo Troncone1, Umberto Malapelle, Immacolata Cozzolino
1Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli Federico II, Naples, Italy. giancarlo.troncone@unina.it
Abstract:
Recent evidences showed that metastatic colorectal cancer (CRC) patients with tumors harboring a KRAS gene mutation do not derive benefit from the administration of epidermal growth factor receptor-directed monoclonal antibodies. Typically, the specimens available for KRAS mutational analysis are formalin-fixed paraffin-embedded (FFPE) primary tumor tissue blocks. However, in patients with rectal tumours undergoing neoadjuvant therapy, the source of FFPE material is limited. In this setting, CRC cytological samples taken from the metastatic site may be exploited. However, these specimens show at least some degree of necrosis; thus, their suitability for the KRAS assay needs to be tested. Here, we show that 18/19 (94.7%) metastatic CRC smears were perfectly adequate for codon 12 and 13 KRAS mutational analysis by direct gene sequencing. Only one case (5.3%) showing abundant necrotic debris and poor cellular preservation was not informative for KRAS status. Codon 12 gene mutations were found in 4/18 (22.2%) of the adequate cases (c35G>T n = 2; c34G>T n = 1; c35G>A n = 1). Concordance between cytological and FFPE samples, both available in 13 patients, occurred in 92.3% (12/13) of the cases. Thus, whenever histological specimens of CRC are notavailable, KRAS testing may be reliably performed on cytological specimens.
Insights
Metastatic colorectal cancer (CRC) patients with KRAS mutations do not benefit from EGFR-targeted therapies. KRAS testing on cytological samples is a reliable alternative when FFPE tissues are unavailable.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Metastatic colorectal cancer (CRC) patients with KRAS mutations do not benefit from epidermal growth factor receptor (EGFR)-directed therapies.
- Formalin-fixed paraffin-embedded (FFPE) primary tumor tissue blocks are typically used for KRAS mutational analysis.
- Limited FFPE material is available for rectal cancer patients undergoing neoadjuvant therapy.
Purpose of the Study:
- To evaluate the suitability of colorectal cancer (CRC) cytological samples from metastatic sites for KRAS mutational analysis.
- To determine the reliability of KRAS testing on cytological specimens when FFPE tissues are scarce.
Main Methods:
- Direct gene sequencing was performed on 19 metastatic CRC cytological samples.
- Suitability for KRAS codon 12 and 13 analysis was assessed.
- Concordance analysis was performed between cytological and FFPE samples in 13 patients.
Main Results:
- 18 out of 19 (94.7%) metastatic CRC cytological smears were adequate for KRAS mutational analysis.
- KRAS codon 12 mutations were identified in 4 out of 18 (22.2%) adequate cases.
- 92.3% concordance was observed between cytological and FFPE samples.
Conclusions:
- CRC cytological samples are a viable and reliable alternative for KRAS mutational analysis when FFPE tissues are unavailable.
- This approach can aid in treatment decisions for patients with metastatic colorectal cancer, particularly those with limited tissue availability.
- KRAS testing on cytological specimens ensures timely and accurate molecular profiling for targeted therapy selection.
