RESUMO
BACKGROUND: In contrast to colon cancer, the implications of reduced lymph node retrieval in rectal cancer are unclear. METHODS: Using the California Cancer Registry, we performed a retrospective cohort study of 4790 patients with stage I - III rectal cancer diagnosed from 2000 to 2007 who underwent tri-modality therapy. Using multivariate Cox proportional hazards models adjusted for age, sex, race, socioeconomic status, T-stage, and lymph node numbers, we evaluated rectal cancer specific survival (RC-SS) in neoadjuvant and adjuvant cohorts in the overall population and amongst those without involved lymph nodes (pN0). RESULTS: Sixty one percent of evaluable patients were treated with neoadjuvant chemoradiation. Although there was no difference in RC-SS between neoadjuvant and adjuvant chemoradiation cohorts, the median number of lymph nodes examined was reduced after neoadjuvant therapy (8 vs. 11, p < 0.0001). Positive lymph nodes were associated with worse RC-SS regardless of sequence, although the effect was numerically stronger for residual lymph nodes in the neoadjuvant cohort. Compared to at least 12, eight or fewer lymph nodes retrieved was associated with worse outcome in both neoadjuvant and adjuvant cohorts. However, no association between reduced lymph nodes examined and RC-SS was seen in the neoadjuvant cohort when the analysis was restricted to pN0 patients. CONCLUSIONS: In this large cohort of rectal cancer patients treated with tri-modality therapy, reduced lymph node retrieval in node negative patients did not provide additional prognostic information in patients treated with neoadjuvant therapy.
Assuntos
Adenocarcinoma/terapia , Excisão de Linfonodo , Linfonodos/patologia , Neoplasias Retais/terapia , Reto/cirurgia , Sistema de Registros , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , California , Quimiorradioterapia , Quimiorradioterapia Adjuvante , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Reto/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: We investigated the somatic mutational pattern of a specific Vlambda light chain variable region (V) gene in rheumatoid arthritis (RA) patients. The Vlambda4B light chain was chosen because of its location on the lambda locus and because of its previously observed use in IgM rheumatoid factors. METHODS: We sequenced 13 different mRNA transcripts of Vlambda4B from the synovium of three different RA patients. These were compared to 31 identifiable Vlambda4B sequences from GenBank, which were obtained from the PBL of patients without RA. RESULTS: A subset of Vlambda4B had a high rate of mutation, especially in the framework regions within the RA synovium. Furthermore, a set of codons within the first complementary determining region of Vlambda4B displayed frequent replacement mutations but did not possess any silent mutations. CONCLUSION: The hypermutation of RA synovial-derived Vlambda4B sequences, especially in the framework areas, may contribute to or may be the result of altered mutational mechanisms and/or prolonged B cell life.
Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Genes de Imunoglobulinas , Mutação em Linhagem Germinativa , Cadeias lambda de Imunoglobulina/genética , Idoso , Sequência de Aminoácidos , Sequência de Bases , Códon/genética , Análise Mutacional de DNA , Primers do DNA/genética , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , RNA Mensageiro/genética , Homologia de Sequência de AminoácidosRESUMO
In order to better characterize the expression of a family of light chains previously expressed in IgM rheumatoid factors, we studied the usage and somatic mutational pattern of the Vlambda4A light chain gene in rheumatoid arthritis (RA) patients. We sequenced 11 different transcripts of Vlambda4A from the synovial tissue of three different RA patients. For comparison, we found 8 rearranged transcripts of Vlambda4A from 4 normal peripheral blood lymphocyte libraries and 1 rearranged transcript from a non-RA con-A-resistant hybridoma in GenBank. A previously undescribed polymorphism of Vlambda4A was noted. Furthermore, conserved replacement mutations in the complementary determining regions, common silent mutations around these replacement mutations, and two subsets of mutated sequences were detected in multiple RA patients. These mutation patterns also correlated with observed consistencies in the rearrangements of the Vlambda4A/Jlambda junction. These data suggest that there is clonal expansion of Vlambda4A light chains in the RA synovium in response to a RA-specific antigen or as the result of an idiotypic response in RA.
