GTPase KRas (7-15)

Primary mucinous adenocarcinomas are uncommon, and their pathogenesis remains unclear. We recently reported the clinicopathologic characteristics of surgically resected mucinous adenocarcinoma, including the frequent involvement of the left and lower lung and absence of central fibrosis. The present study attempted to clarify the pathogenesis of mucinous adenocarcinoma based on KRAS mutation status. We selected 45 mucinous adenocarcinoma cases from among 2474 surgically resected primary lung adenocarcinomas. Of these, 22 had a KRAS mutation (48.9%), whereas only 7 (15.6%) had an epidermal growth factor receptor mutation, and 2 cases had both mutations. The mucinous adenocarcinomas with KRAS mutations were located in the lower lung lobe significantly more often (P < .05) than were tumors without KRAS mutation. The mucinous adenocarcinoma cases with KRAS mutations also had a significantly lower frequency of nuclear atypia (P < .05). We compared the degree of immunostaining for matrix metalloproteinase-7 (MMP-7), laminin-5, and geminin in the mucinous adenocarcinoma with and without KRAS mutation. The proportion of geminin-positive cells was lower among the cases with a mutation than among those without (0.7% versus 2.1%; P < .05). No significant differences in the extent of staining of the other markers were observed between the groups. The current study clearly demonstrated that mucinous adenocarcinomas with KRAS mutations have clinicopathologic characteristics different from those of mucinous adenocarcinoma without such mutations.

In carcinogenesis, KRAS is an essential oncogene that plays a key function. The polymorphism of rs61764370 is a candidate for cancer susceptibility in KRAS3' untranslated region. The current study aimed to determine the role and impact of the KRAS gene polymorphism (rs61764370 T>G) on the risk of ovarian cancer development in the Iraqi population. In total, 84 ovarian cancer patients and 28 ovarian benign tumors were involved in a case-control study. DNA extraction from the formalin-fixed/paraffin-embedded tissues, followed by the sequencing of PCR products was carried out in genetic analysis for the detection of the KRAS polymorphism (rs61764370 T>G). The results showed that the frequencies of the KRAS gene polymorphism (rs61764370) in ovarian cancer patients were 78 (92.85%) and 6 (7.15%) with genotypes homozygote TT and heterozygote TG, respectively. These corresponding values in patients with benign ovarian tumors were 25 (89.3%) and 3 (10.7%) with homozygote TT and heterozygote TG, respectively. None of the patients either with malignant or benign tumors have been detected with homozygote genotype GG. Genotype frequency of the TT and TG showed that the heterozygote TT genotype vs. TG and T allele vs. G allele were more frequent in malignant and benign tumors (P≤0.01). Statistically, there was no association between the KRAS polymorphism and the clinical characteristics of ovarian cancer patients, such as age, family history, menopause, histological type, tumor size, or tumor stage. In conclusion, a significant association was found between rs61764370 and the risk of ovarian cancer in the Iraqi population, particularly those with genotypes homozygote TT. On the other hand, genotypes had no relationship with any of the clinical characteristics of ovarian cancer patients. Additional well-designed studies with larger sample sizes are recommended to validate the precise role of KRAS LCS6 variations in ovarian cancer risk.

Background/aims: Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations influence survival after hepatectomy for colorectal liver metastases (CRLM). However, their prognostic significance has never been evaluated in patients who undergo Associating Liver Partition and Portal vein occlusion for Staged hepatectomy (ALPPS). Methods: Between June 2011 and March 2016, 26 patients underwent ALPPS for CRLM. Complications were classified according to the Clavien-Dindo classification. Bi- and multivariate cox analyses were performed to evaluate variables potentially associated with survival. Results: Overall, morbidity grade ≥3a and 90-day mortality were 38.5 and 0%, respectively. The median follow-up from the time of discharge was 21.5 months (interquartile range 9.6-35.6). One- and 3-year overall survival (OS) was 83.4 and 48.9%, respectively. Patients with mutated (MT) KRAS had a median OS of 15.3 vs. 38.3 months for those with wild-type (WT) KRAS (p < 0.0001). Median disease-free survival was 7.9, 5.6 vs. 12.3 months for MT and WT KRAS, respectively (p = 0.023). KRAS mutation was found to be an independent risk factor for OS (hazard ratio 7.15, 95% CI 1.50-34.11; p = 0.014). Conclusion: KRAS mutation is an independent predictor of poor survival after ALPPS. This finding will help to optimize patient selection, both avoiding futile surgical indication and maximizing the benefit for patients with extensive disease who are otherwise subjected to high-risk aggressive surgery.