ABSTRACT
Cancer of unknown primary origin (CUP) had a poor prognosis, determined by clinico-histological characteristics, partly due to the lack of insights on its biology. We screened tumour DNA from 87 patients with CUP for CTNNB1 (coding exons 2,3,4,5), MET (coding exon 18), PIK3CA (coding exons 9,20), KRAS (coding exons 1,2), BRAF (coding exon 15) gene mutations by using dd-sequencing and evaluated their impact on prognosis. Mutated gene incidences in the 87 CUP cases were: KRAS 11 (12.6 %), BRAF 5 (5.7 %), PIK3CA 8 (9 %), MET 6 (6.7 %) and CTNNB1 18 (20.7 %). Several mutations in the KRAS gene were not the commonly encountered mutations in other solid tumours. Activating mutations were observed in 10.2 % in KRAS, 4.5 % in BRAF, 6.6 % in PIK3CA, 4.5 % in MET, and 19.5 % in CTNNB1. Activating mutations in PIK3CA coding exon 9 were inversely correlated with MET coding exon 18 activating mutations (p = 0.036). MET activating mutations were prognostic for poor Progression-Free Survival (median PFS 5 vs 9 months, p = 0.009) and Overall Survival (median OS 7 vs 20 months, p = 0.005). The complex profile of either CTNNB1 or MET mutations also had an adverse prognostic significance (median OS 11 vs 21 months, p = 0.015). No other gene mutation exhibited prognostic significance. In multivariate analysis, poor performance status, male gender, visceral disease and adenocarcinoma histology, but not gene mutations, were independently associated with poor patient outcome. CTNNB1 gene mutations are frequent, and along with MET mutations have an adverse prognostic effect in patients with CUP.
Subject(s)
Neoplasms, Unknown Primary/genetics , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-met/genetics , Proto-Oncogene Proteins p21(ras)/genetics , beta Catenin/genetics , Adult , Aged , Base Sequence , DNA Primers , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
Paraquat is a synthetic, nonselective, contact herbicide, which causes injury to tissues following contact. When ingested in sufficient amounts, paraquat has life-threatening effects on the gastrointestinal tract, lungs, kidney, liver, heart and other organs. This is a case report of a 15-year-old girl from an agricultural area who was admitted to hospital for treatment. She presented with discomfort, nausea and vomiting. She had drunk a small wine glass full of paraquat. After 18 days in the hospital, the girl developed neutropenia. This is the first reported case of paraquat poisoning-induced neutropenia.
