Objective: A difference in survival rates between black and white patients with cancer of the corpus uteri is well established. This study was conducted to determine whether the overexpression of HER2/neu oncogene is ...Objective: A difference in survival rates between black and white patients with cancer of the corpus uteri is well established. This study was conducted to determine whether the overexpression of HER2/neu oncogene is associated with poor outcome in uterine serous papillary endometrial cancer, which is a highly aggressive variant of endometrial cancer, and whether a racial difference in the frequency of HER2/neu overexpression may contribute to the disparity in endometrial cancer survival. Study design: Immunohistochemical evaluation was used to examine HER2/neu expression in paraffin blocks from 27 women with stage IA to IV uterine serous papillary endometrial cancer. Univariable analysis was performed and followed by multivariable analysis with Cox’ s proportional hazard model to evaluate whether HER2/neu expression was associated with poor outcome in uterine serous papillary endometrial cancer. Results: Black patients tended to be younger (P =. 02) and have higher HER2/neu expression than white patients (trend P =. 02). Seven of 10 black patients (70% ) showed heavy (3+ ) expression, compared with 4 of 17 white patients (24% ; P =. 04). The association of heavy HER2/neu expression with race persisted after age was controlled through stratification (P =. 05). Earlier deaths from uterine serous papillary endometrial cancer were seen among heavy HER2/neu expressers (P =. 002), black patients (P =. 04), and patients ≤ 65 years old (P =. 04). However, multivariate Cox regression showed that short survival was associated significantly with heavy HER2/neu expression (P =. 02) but not with age (P =. 07) or race (P =. 35), which indicates that HER2/neu expression accounted for much of the race disparity in survival in this patient population. Conclusion: Overexpression of HER2/neu in uterine serous papillary endometrial cancer is an independent variable that is associated with poor outcome, occurs more frequently in black women, and may contribute to racial disparity in survival. HER2/neu expression may guide clinical treatment of patients with uterine serous papillary endometrial cancer and may have implications for the implementation of novel treatment strategies.展开更多
Objective. To evaluate the potential of human papillomavirus (HPV) type 16 and 18 E7 antigen-loaded autologous dendritic cells (DC) as a therapeutic cellular vaccine in a case series of cervical cancer patients harbor...Objective. To evaluate the potential of human papillomavirus (HPV) type 16 and 18 E7 antigen-loaded autologous dendritic cells (DC) as a therapeutic cellular vaccine in a case series of cervical cancer patients harboring recurrent/metastatic disease refractory to standard treatment modalities. Methods. Autologous monocyte-derived DC were pulsed with recombinant HPV16 E7 or HPV18 E7 oncoproteins and administered to 4 cervical cancer patients. Vaccinations were followed by subcutaneous administration twice daily of low doses of human recombinant interleukin- 2 (1 × 106 IU/m2) from day 3 to day 7. Safety, toxicity, delayed type hypersensitivity reactions (DTH), clinical responses, and induction of serological and cellular immunity against HPV16/18 E7 were monitored. Results. The vaccine was well- tolerated in all patients and no local or systemic side effects or toxicity were recorded. Three out of four patients were found to be significantly immunocompromised before starting the vaccination treatment, as assessed by DTH with a panel of recall antigens. Specific humoral and cellular CD4+ T cell responses to the E7 vaccine were detected in 2 patients, as detected by ELISA and by IFN- γ ELISpot assays, respectively. Increased numbers of E7- specific IFN- γ secreting CD8+ T cells were detected in all patients after vaccination. Swelling and induration (i.e., a positive DTH response) to the intradermal injection of HPV E7 oncoprotein and/or irradiated autologous tumor cells were detected in two patients after six vaccinations. No objective clinical responses were observed. However, both patients who developed a positive DTH to the vaccine experienced a slow tumor progression (i.e., 13 months survival)while DTH unresponsive patients died within 5 months from the beginning of therapy. Conclusions. Autologous DC pulsed with HPV16/18 E7 proteins can induce systemic B and T cell responses in patients unresponsive to standard treatment modalities. However, treatment-induced immunosuppression may impose severe limitations on the efficacy of active vaccination strategies in late stage cervical cancer patients. DC-based vaccination trials are warranted in immunocompetent cervical cancer patients with early stage disease and/or limited tumor burden, and at significant risk for tumor recurrence or disease progression.展开更多
Objective. To evaluate and compare HER2/neu protein overexpression and gene amplification in uterine serous papillary endometrial cancer (USPC). Study design. Immunohistochemical (IHC) and fluorescent in situ hybridiz...Objective. To evaluate and compare HER2/neu protein overexpression and gene amplification in uterine serous papillary endometrial cancer (USPC). Study design. Immunohistochemical (IHC) and fluorescent in situ hybridization (FISH) assays were used to analyze and compare HER2/neu protein expression and gene amplification, respectively, in paraffin blocks from 26 women harboring stage IA to IV USPC treated at the University of Arkansas for Medical Sciences from 1997 to 2004. Chromosome 17 polysomy status by FISH was also assessed in all specimens. Results. Moderate-to-strong expression of HER2/neu protein was noted in 16 (62% ) of 26 USPC samples evaluated, with 7 (27% ) samples showing moderate staining (2? ) and 9 (35% ) showing strong staining (3? ) for HER2/neu. Amplification of the ERBB2 gene by FISH was observed in 11 of the 26 (42% ) cases. Protein overexpression and gene amplification were found to correlate in 100% (9 of 9) of the 3? positive tumors and 2 out of 7 (29% ) of the 2? positive tumors. Heterogeneity was noted in 3 cases in the amplification of the HER2/neu gene within the same tumor samples with pockets of amplified tumor cells amidst nonamplified tumor cells. None of the 10 USPC cases scored by IHC as 0 or 1? was found positive for ERBB2 amplification by FISH. Conclusions. Amplification of the HER2/neu oncogene represents a common finding in USPC. FISH analysis should be used for confirmation of gene amplification in USPC showing 2? expression of HER2/neu. Prior screening and selection of appropriate immunohistochemistry-positive areas may be beneficial in the selection of some USPC patients undergoing FISH analysis.展开更多
文摘Objective: A difference in survival rates between black and white patients with cancer of the corpus uteri is well established. This study was conducted to determine whether the overexpression of HER2/neu oncogene is associated with poor outcome in uterine serous papillary endometrial cancer, which is a highly aggressive variant of endometrial cancer, and whether a racial difference in the frequency of HER2/neu overexpression may contribute to the disparity in endometrial cancer survival. Study design: Immunohistochemical evaluation was used to examine HER2/neu expression in paraffin blocks from 27 women with stage IA to IV uterine serous papillary endometrial cancer. Univariable analysis was performed and followed by multivariable analysis with Cox’ s proportional hazard model to evaluate whether HER2/neu expression was associated with poor outcome in uterine serous papillary endometrial cancer. Results: Black patients tended to be younger (P =. 02) and have higher HER2/neu expression than white patients (trend P =. 02). Seven of 10 black patients (70% ) showed heavy (3+ ) expression, compared with 4 of 17 white patients (24% ; P =. 04). The association of heavy HER2/neu expression with race persisted after age was controlled through stratification (P =. 05). Earlier deaths from uterine serous papillary endometrial cancer were seen among heavy HER2/neu expressers (P =. 002), black patients (P =. 04), and patients ≤ 65 years old (P =. 04). However, multivariate Cox regression showed that short survival was associated significantly with heavy HER2/neu expression (P =. 02) but not with age (P =. 07) or race (P =. 35), which indicates that HER2/neu expression accounted for much of the race disparity in survival in this patient population. Conclusion: Overexpression of HER2/neu in uterine serous papillary endometrial cancer is an independent variable that is associated with poor outcome, occurs more frequently in black women, and may contribute to racial disparity in survival. HER2/neu expression may guide clinical treatment of patients with uterine serous papillary endometrial cancer and may have implications for the implementation of novel treatment strategies.
文摘Objective. To evaluate the potential of human papillomavirus (HPV) type 16 and 18 E7 antigen-loaded autologous dendritic cells (DC) as a therapeutic cellular vaccine in a case series of cervical cancer patients harboring recurrent/metastatic disease refractory to standard treatment modalities. Methods. Autologous monocyte-derived DC were pulsed with recombinant HPV16 E7 or HPV18 E7 oncoproteins and administered to 4 cervical cancer patients. Vaccinations were followed by subcutaneous administration twice daily of low doses of human recombinant interleukin- 2 (1 × 106 IU/m2) from day 3 to day 7. Safety, toxicity, delayed type hypersensitivity reactions (DTH), clinical responses, and induction of serological and cellular immunity against HPV16/18 E7 were monitored. Results. The vaccine was well- tolerated in all patients and no local or systemic side effects or toxicity were recorded. Three out of four patients were found to be significantly immunocompromised before starting the vaccination treatment, as assessed by DTH with a panel of recall antigens. Specific humoral and cellular CD4+ T cell responses to the E7 vaccine were detected in 2 patients, as detected by ELISA and by IFN- γ ELISpot assays, respectively. Increased numbers of E7- specific IFN- γ secreting CD8+ T cells were detected in all patients after vaccination. Swelling and induration (i.e., a positive DTH response) to the intradermal injection of HPV E7 oncoprotein and/or irradiated autologous tumor cells were detected in two patients after six vaccinations. No objective clinical responses were observed. However, both patients who developed a positive DTH to the vaccine experienced a slow tumor progression (i.e., 13 months survival)while DTH unresponsive patients died within 5 months from the beginning of therapy. Conclusions. Autologous DC pulsed with HPV16/18 E7 proteins can induce systemic B and T cell responses in patients unresponsive to standard treatment modalities. However, treatment-induced immunosuppression may impose severe limitations on the efficacy of active vaccination strategies in late stage cervical cancer patients. DC-based vaccination trials are warranted in immunocompetent cervical cancer patients with early stage disease and/or limited tumor burden, and at significant risk for tumor recurrence or disease progression.
文摘Objective. To evaluate and compare HER2/neu protein overexpression and gene amplification in uterine serous papillary endometrial cancer (USPC). Study design. Immunohistochemical (IHC) and fluorescent in situ hybridization (FISH) assays were used to analyze and compare HER2/neu protein expression and gene amplification, respectively, in paraffin blocks from 26 women harboring stage IA to IV USPC treated at the University of Arkansas for Medical Sciences from 1997 to 2004. Chromosome 17 polysomy status by FISH was also assessed in all specimens. Results. Moderate-to-strong expression of HER2/neu protein was noted in 16 (62% ) of 26 USPC samples evaluated, with 7 (27% ) samples showing moderate staining (2? ) and 9 (35% ) showing strong staining (3? ) for HER2/neu. Amplification of the ERBB2 gene by FISH was observed in 11 of the 26 (42% ) cases. Protein overexpression and gene amplification were found to correlate in 100% (9 of 9) of the 3? positive tumors and 2 out of 7 (29% ) of the 2? positive tumors. Heterogeneity was noted in 3 cases in the amplification of the HER2/neu gene within the same tumor samples with pockets of amplified tumor cells amidst nonamplified tumor cells. None of the 10 USPC cases scored by IHC as 0 or 1? was found positive for ERBB2 amplification by FISH. Conclusions. Amplification of the HER2/neu oncogene represents a common finding in USPC. FISH analysis should be used for confirmation of gene amplification in USPC showing 2? expression of HER2/neu. Prior screening and selection of appropriate immunohistochemistry-positive areas may be beneficial in the selection of some USPC patients undergoing FISH analysis.
