ABSTRACT
Cervical cancer is one of the leading causes of cancer-associated mortality among females; however, the underlying molecular mechanisms of its carcinogenesis remain largely unclear. Previous comprehensive genomic studies have revealed prevalent estrogen receptor 1 (ESR1) mutations in breast cancer, which are rare in certain other types of cancer. To the best of our knowledge, it is unknown whether ESR1 mutations also exist in cervical cancer. Considering the evidence that cervical cancer shares certain genetic aberrations with breast cancer, and that the progression of both breast and cervical cancers can be affected by estrogen, it is possible that cervical cancer may also harbor ESR1 mutations. In the present study, a total of 260 Chinese cervical cancer samples with distinct subtypes were tested for the presence of ESR1 mutations. A total of three heterozygous missense ESR1 mutations, p.K303R (c.908A>G), p.T311M (c.932C>T) and p.Y537C (c.1610A>G), were identified in 3/207 (1.4%) cervical squamous cell carcinoma samples, which were absent in 27 adenosquamous carcinomas and 26 adenocarcinomas samples. Of the three individuals with an ESR1mutation, 1 patient was also diagnosed with ovarian endometriosis and the other 2 patients were diagnosed with a uterine fibroid. A bioinformatics analysis suggested that these ESR1 mutations may be pathogenic by promoting the development of cervical cancer. Furthermore, a previous comprehensive study confirmed that individuals with cervical squamous cell carcinoma possessed ESR1 mutations. These combined studies indicate that ESR1 mutations may participate in the carcinogenesis of cervical squamous cell carcinoma, albeit at a low frequency. In conclusion, the present study identified three potentially pathogenic ESR1 mutations in Chinese cervical squamous cell carcinoma samples, but not in other subtypes.
ABSTRACT
This study was purpose to investigate the immunophenotype of leukemia promyelocytes (LP) and its significance through retrospective analysis of LP immunophenotype and data in new diagnosis of patients with acute promyelocytic leukemia (APL). The immunophenotype of leukemia cells in 71 APL patients was analyzed by means of 6 color immunotyping. The results indicated that MPO, CD33 and CD13 were consistently expressed in leukemia cells of all APL cases with highest average percentages (> 88%) of positive cells among all studied markers. CD117 was found to be positive in 50.7%, and its average percentage of positive cells was 52.5%. Leukemia cells in about 10% cases expressed CD15 weakly, and its average percentage of positive cells was 42.5%. CD34 and HLA-DR showed decreased expressions in a small number of cases and were negative in the others. CD2 and CD56 were weakly expressed in nearly 25% APL cases, and the average percentage of positive cells were 39.3% and 42.3%, respectively. Thereby, it is of the opinion that the typical immunophenotype is characterized by MPO(+)CD13(+)CD33(+)CD117(±)CD15(±)CD34(-)HLA-DR(-) in APL. CD2 and CD56 were expressed significantly higher in CD34(+) or HLA-DR(+) group (including CD34(+) HLA-DR(+), CD34(+) HLA-DR(-) and CD34(-)HLA-DR(+)) than in CD34(-) and HLA-DR(-) group. Significant differences were also found in WBC and platelet counts, percentage of peripheral blood leukemic promyelocytes and the expression of CD13 among CD15 < 10%, 10% < CD15 < 20% and CD15 > 20% groups. It is concluded that the APL has a characteristic immunophenotypic profile, flow cytometric immunophenotyping may be considered as a useful tool for rapid recognition of APL and also may be considered to have an important significance for analysing origin of leukemic cells and clinical outcome of patients.
