RESUMO
The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAFV600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety-three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAFV600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAFV600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA/genética , Programas de Rastreamento/métodos , Proteína 1 Homóloga a MutL/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , China/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Variações do Número de Cópias de DNA/genética , Feminino , Predisposição Genética para Doença/genética , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
The first phase transfer-catalysed direct γ-substitution of Morita-Baylis-Hillman carbonates of isatins with 3-substituted oxindoles has been developed, which affords 3-alkenyl-oxindole ring-fused 3,3'-disubstituted oxindoles in up to 83% yield under mild reaction conditions. Furthermore, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3 and human leukemia cells K562, using MTT-based assays with the commercially available standard drug Cisplatin as a positive control. Gratifyingly, compounds 3aa, 3ba and 3ca exhibited comparable in vitro inhibitory activities against human prostate cancer cells (PC-3) to Cisplatin. What's more, 3ba also had a good inhibition ability against human leukemia cells K562. These results indicate that 3-alkenyl-oxindole ring-fused 3,3'-disubstituted oxindole analogs may be potential lead compounds for further biological screening.
