Clinicopathological Associations of K-RAS and N-RAS Mutations in Indonesian Colorectal Cancer Cohort

Levi, Michael H.; Prayogi, G.; Sastranagara, Farid; Sudianto, Edi; Widjajahakim, Grace; Gani, Winiarti; Mahanadi, Albert; Agnes, Jocelyn; Khairunisa, Bela Haifa; Utomo, Ahmad

doi:10.1007/s12029-016-9901-x

Cited by 14 publications

(13 citation statements)

References 28 publications

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“…In addition, others and we had described the utility of split peak pattern of PCR HRM previously to screen for RAS and EGFR mutations rapidly. 19 , 20 …”

Section: Discussionmentioning

confidence: 99%

Uncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients

Syahruddin¹,

Wulandari²,

Muktiati³

et al. 2018

LCTT

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PurposeWe aimed to evaluate the distribution of individual epidermal growth factor receptor (EGFR) mutation subtypes found in routine cytological specimens.Patients and methodsA retrospective audit was performed on EGFR testing results of 1,874 consecutive cytological samples of newly diagnosed or treatment-naïve Indonesian lung cancer patients (years 2015–2016). Testing was performed by ISO15189 accredited central laboratory.ResultsOverall test failure rate was 5.1%, with the highest failure (7.1%) observed in pleural effusion and lowest (1.6%) in needle aspiration samples. EGFR mutation frequency was 44.4%. Tyrosine kinase inhibitor (TKI)-sensitive common EGFR mutations (ins/dels exon 19, L858R) and uncommon mutations (G719X, T790M, L861Q) contributed 57.1% and 29%, respectively. Approximately 13.9% of mutation-positive patients carried a mixture of common and uncommon mutations. Women had higher EGFR mutation rate (52.9%) vs men (39.1%; p<0.05). In contrast, uncommon mutations conferring either TKI responsive (G719X, L861Q) or TKI resistance (T790M, exon 20 insertions) were consistently more frequent in men than in women (67.3% vs 32.7% or 69.4% vs 30.6%; p<0.05). Up to 10% EGFR mutation–positive patients had baseline single mutation T790M, exon 20 insertion, or in coexistence with TKI-sensitive mutations. Up to 9% patients had complex or multiple EGFR mutations, whereby 48.7% patients harbored TKI-resistant mutations. One patient presented third-generation TKI-resistant mutation L792F simultaneously with T790M.ConclusionRoutine diagnostic cytological techniques yielded similar success rate to detect EGFR mutations. Uncommon EGFR mutations were frequent events in Indonesian lung cancer patients.

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“…In addition, others and we had described the utility of split peak pattern of PCR HRM previously to screen for RAS and EGFR mutations rapidly. 19 , 20 …”

Section: Discussionmentioning

confidence: 99%

Uncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients

Syahruddin¹,

Wulandari²,

Muktiati³

et al. 2018

LCTT

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“…ADCCR patients with wt KRAS status have a good response to anti-EGFR therapy [8], [18]. This study shows that 62.9% of ADCCR cases in this study had a good response to anti-EGFR, such as cetuximab and panitumumab [1], [3], [11], [18].…”

Section: Discussionmentioning

confidence: 90%

“…In ADCCR wt KRAS will always be active because EGF stimulates continuously. ADCCR patients with wt KRAS have a good response to anti-epidermal Growth Factor Receptor (EGFR) drugs such as cetuximab and panitumumab [1], [9], [10], [11]. In contrast, mutant KRAS was not responsive to anti-EGFR inhibition [1], [3], [12].…”

Section: Introductionmentioning

confidence: 99%

The Correlation of KRAS Gene Expression and P53 Immunoexpression In Colorectal Adenocarcinoma

Rachmawati¹,

Yulianti²,

Hernowo³

et al. 2019

Open Access Maced J Med Sci

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BACKGROUND: Colorectal Adenocarcinoma (ADCCR) is the third most cancer not only in the world but also in Indonesia. There were 623 cases of ADCCR at Dr Hasan Sadikin hospital within 2015-2017. Both KRAS and TP53 mutation are known as genes which involve in carcinogenesis through the same pathway, namely the chromosomal instability pathway. In West Java, researches focusing on mutation KRAS and p53 also a correlation between both biomarkers among ADCCR patients are still limited. AIM: Therefore, this research aimed to perceive a correlation between KRAS gene expression with p53 immunoexpression in ADCCR.METHODS: Cross section research design was performed to 62 cases of ADCCR as paraffin block taken from 4 hospitals in West Java, including Dr Hasan Sadikin hospital Bandung, Santosa hospital Bandung, Borromeus hospital Bandung and Syamsudin hospital Sukabumi from January 1st 2014 to 31s November 2018. KRAS mutation gene data taken from secondary data at molecular laboratory in Ciptomangunkusumo Hospital Jakarta and Dr Sardjito Hospital Jogjakarta, while the detection of p53 immunoexpression data using immunohistochemical staining was carried out in the Laboratorium of Anatomical Pathology of Padjadjaran University (Dr Hasan Sadikin Hospital). All data were analysed using Chi-Square test with p-value < 0,05 of significant level then proceeded with Stata ver.11 for windows.RESULTS: The results of this study showed that KRAS gene expressions from 62 sample consist of 39 wild type KRAS (62.39%) and 23 mutant KRAS (37.1%). The p53 immunoexpression consists of 27 negative cases (non-mutant p53) and 35 mutant p53, which includes 10 cases as focal expression (16.33%) and 25 cases as diffuse expressions (40.33%). There is a significant association between KRAS gene expression and p53 immunoexpressions in ADCCR (p = 0.04), with mild positive correlation (Rho 0.28). CONCLUSION: This study concluded that KRAS and p53 mutations are involved in carcinogenesis, and the p53 mutation is a more dominant risk factor than KRAS mutation among West Java people. P53 mutations with diffuse pattern tend to express mutant KRAS while p53 negative and having a focal pattern tend to express wt KRAS.

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“…PCR and direct sequencing of K-RAS mutations were performed as described 25. Briefly, RAS SplitSCAN (KalgenDNA, Jakarta, Indonesia) HRM primers were used to screen a hotspot mutation of exon 2 of the K-RAS gene.…”

Section: Methodsmentioning

confidence: 99%

Impact of smoking on frequency and spectrum of K-RAS and EGFR mutations in treatment naive Indonesian lung cancer patients

Masykura

Zaini²,

Syahruddin³

et al. 2019

LCTT

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Background: Indonesia has the highest cigarette consumption in the world. We explored the clinical impact of smoking on the prevalence of EGFR and K-RAS mutations and survival in this prospective study. Methods: 143 treatment naive lung cancer patients were recruited from Persahabatan Hospital, a national tertiary hospital. DNA from cytological specimens had been extracted and genotyped for both EGFR and K-RAS mutations using a combination of PCR high resolution melting, restriction fragment length polymorphism (RFLP) and direct DNA sequencing. Results: EGFR mutation frequency in never smokers (NS) and ever smokers (ES) were 75% and 56% ( p = 0.0401), respectively. In this cohort, the overall K-RAS mutation rate was 7%. Neither gender nor smoking history were associated with K-RAS mutation significantly. However, K-RAS transversion mutations were more common in male ES than transition mutations. Smoking history did not affect EGFR and K-RAS mutation frequencies in women. Concurrent EGFR / K-RAS mutation rate was 2.8% (4 of 143 patients). Four out of 91 EGFR mutation positive patients (4.4%) had simultaneous K-RAS mutation. Conclusions: In region where cigarette consumption is prevalent, smoking history affected frequencies of EGFR and K-RAS mutations, mainly in males.

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Clinicopathological Associations of K-RAS and N-RAS Mutations in Indonesian Colorectal Cancer Cohort

Abstract: Combination of PCR HRM with either RFLP or direct DNA sequencing was useful to detect K-RAS exon 2 and extended RAS mutations, respectively. Frequency of all RAS mutations in stage IV Indonesian (41%) was similar among Asians (41-49%), which tend to be lower than western (55%) CRC.

Cited by 14 publications

References 28 publications

Uncommon <em>EGFR</em> mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients

Uncommon <em>EGFR</em> mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients

The Correlation of KRAS Gene Expression and P53 Immunoexpression In Colorectal Adenocarcinoma

<p>Impact of smoking on frequency and spectrum of <em>K-RAS</em> and <em>EGFR </em>mutations in treatment naive Indonesian lung cancer patients</p>

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