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Mutational analysis of KRAS and its clinical implications in cervical cancer patients.

ABSTRACT: The predictive and prognostic role of KRAS mutations in cervical cancer remains inconclusive. The aim of this study was to explore the clinicopathological and prognostic relevance of KRAS mutations in invasive cervical cancers (ICC).Reverse transcription polymerase chain reaction (PCR) and Sanger sequencing were employed to detect KRAS mutations in 876 ICC patients. Quantitative real-time PCR was used to detect human papillomavirus (HPV) 16 and HPV 18.Non-synonymous mutations of KRAS were identified in 30 (3.4%) patients. These mutations were more common in non-squamous cell carcinoma than in squamous cell carcinoma (SCC) (8.2% vs. 2.2%, respectively, p<0.001) and were associated with HPV 18 infection (p=0.003). The prevalence of mutations was highest (18.2%) in the uncommon histological subtypes followed by adenocarcinoma (AC, 7.3%) and adenosquamous carcinoma (ASC, 5.8%). During the median follow-up of 55 months, compared to patients with wild-type KRAS, a greater percentage of patients with mutant KRAS relapsed (20.0% vs. 42.9%, respectively, p=0.007). The 3-year relapse-free survival was poorer in patients with mutant KRAS than in patients without KRAS mutations (57.1% vs. 81.9%, respectively, p=0.001). Furthermore, the multivariate analysis showed that the presence of a KRAS mutation was an independent predictor for disease recurrence (hazard ratio [HR]=2.064; 95% confidence interval [CI]=1.125-3.787; p=0.019).KRAS mutations were predominant in non-SCCs of the cervix and were associated with HPV 18 infection. A combination of KRAS mutation detection and HPV genotyping would be useful in identifying patient with poor prognosis for further interventions.

SUBMITTER: Jiang W

PROVIDER: S-EPMC5709530 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Mutational analysis of KRAS and its clinical implications in cervical cancer patients.

Jiang Wei W Xiang Libing L Pei Xuan X He Tiancong T Shen Xuxia X Wu Xiaohua X Yang Huijuan H

Journal of gynecologic oncology 20180101 1

<h4>Objective</h4>The predictive and prognostic role of KRAS mutations in cervical cancer remains inconclusive. The aim of this study was to explore the clinicopathological and prognostic relevance of KRAS mutations in invasive cervical cancers (ICC).<h4>Methods</h4>Reverse transcription polymerase chain reaction (PCR) and Sanger sequencing were employed to detect KRAS mutations in 876 ICC patients. Quantitative real-time PCR was used to detect human papillomavirus (HPV) 16 and HPV 18.<h4>Result ...[more]

PMID: 29185262

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Project description:BackgroundWe previously reported rare regressive genetic trajectories of KRAS pathogenic mutations as a specific hallmark of the genuine oligometastatic status in colorectal cancer (CRC).MethodsSurvival and prognostic impact of disease extent in 140 metastatic CRC patients were evaluated through the Kaplan-Meyer curves and the Log-Rank test. KRAS mutations were assessed through the Illumina NovaSeq 6000 platform and TruSight™ Oncology 500 kit. HLA typing was carried out by PCR with sequence-specific oligonucleotides. Lymphocyte densities in tumors were expressed as cells per square millimeter. NKs isolated and CD8+ from NK-depleted PBMCs were characterized through flow cytometry. CD107a externalization was evaluated as NKs/CD8 cytotoxicity toward human colon cancer cells HT29, SW620, HCT116, and LS174T carrying different KRAS mutations.ResultsThe oligometastatic status was a strong and independent variable for survival (HR: 0.08 vs. polymetastatic disease; 95% CI: 0.02-0.26; p < 0.001). Eighteen oligometastatic patients were selected. Twelve were alive at the last follow-up, and 9 were characterized. Genetic regression of KRAS was observed in 3 patients: patient (PAT)2, PAT5, and PAT8. PAT2 and PAT5 presented the highest levels of GrzB+ lymphocytes in the tumor cores of the metastases (120 ± 11.2 and 132 ± 12.2 cells/mm2, respectively). Six out of 9 patients (67%), including PAT2 and PAT5, expressed HLA-C7. Twopatients (PAT2 and PAT5) presented high CD3+/CD8+-dependent cytotoxicity against HLA-C7+ SW620 cells (p.G12V-mutated cells), which was consistent with their observed mutational regression (p.G12V/p.G13D in primary→p.G13D in metastatic tumor).ConclusionsWe provide evidence that CD3+/CD8+ lymphocytes from oligometastatic CRC patients display differential cytotoxicity against human colon cancer cells carrying KRAS mutations. This could provide an interesting basis for monitoring oligometastatic disease and developing future adoptive immunotherapies.

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Mutational analysis of KRAS and its clinical implications in cervical cancer patients.

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Mutational analysis of KRAS and its clinical implications in cervical cancer patients.

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