ABSTRACT
BACKGROUND: Increased Aurora kinase A gene copy number (AURKA-CN) has been reported in metastatic colorectal cancer (mCRC), with unknown relationship to clinical outcome. We correlated increased AURKA-CN in mCRC tumours with KRAS mutation status, overall and progression-free survival (OS, PFS). METHODS: Sixty-one mCRC tumours were analysed for AURKA-CN using q-PCR, and KRAS mutation status by direct sequencing. Expression of AURKA protein was analysed by immunohistochemistry. Cox-proportional hazard method, Kaplan-Meier curves and log-rank statistics were used to estimate and compare the hazard ratios and median survival between the groups. RESULTS: In all, 68% of tumour exhibited high AURKA-CN, and 29% had a KRAS mutation, without correlation between the two. Patients with high AURKA-CN tumours had longer median OS (48.6 vs 18.8 months, P=0.01), with stronger trend among KRAS wild-type tumours (median OS not reached vs 18.8 months, P=0.003). Progression-free survival was longer on first-line or second-line chemotherapy among patients with KRAS wild-type and high vs low AURKA-CN (first: 17.6 vs 5.13 months, P=0.04; second: 10.4 vs 5.1 months, P=0.01). AURKA-CN level did not affect outcomes among patients with KRAS mutant tumours. CONCLUSION: Increased AURKA-CN is common in mCRC tumours and is associated with longer OS and longer PFS during chemotherapy, particularly in KRAS wild-type tumours.
Subject(s)
Colorectal Neoplasms/genetics , Gene Dosage , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Aurora Kinase A , Aurora Kinases , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Disease-Free Survival , Female , Humans , Male , Middle Aged , Mutation , Neoplasm Metastasis , Prognosis , Proto-Oncogene Proteins p21(ras)ABSTRACT
A seroepidemiological survey was carried out with the aim of establishing whether or not HIV 2 infection could be detected in Western Sicily. Two groups of sera were tested by EIA and WB assay against HIV 1 and HIV 2. 200 sera taken from North African immigrants in the Mazara del Vallo area, and 297 samples taken from AIDS-high risk groups individuals living in Palermo. None of the North African sera was positive to HIV 1 and/or HIV 2 by either techniques. 118 of the 297 sera from Palermo were HIV 1 positive by both techniques; 69 thereof also reacted to HIV 2 by EIA. Only six of these were confirmed by WB assay, showing a clear reactivity against the 140 and 105 HIV 2 glycoproteins. However, all six sera were considered merely cross-reactive to HIV 2, since none of them had neutralizing antibody to HIV 2 and the cross reactivity to glycoproteins of HIV 2 could be removed by absorbing them with HIV 1 infected cells. It seems therefore that HIV 2 has not yet reached our area. Early detection of the possible presence of this virus in our country could be obtained by improving both the surveillance and the effectiveness of laboratory tools for HIV 2 diagnosis.
