Kevin L. Hall

Asian-Pacific Islander race independently predicts poor outcome in patients with endometrial cancer☆

OBJECTIVE The Department of Defense health care system provides access to care without respect to age, race, or socioeconomic status. We sought to determine the effect of race as a predictor of survival in patients with endometrial cancer treated in the Department of Defense medical system. METHODS Information on patients with endometrial carcinoma was extracted from the Department of Defense centralized tumor registry for the period 1988 to 1995. Data included age at diagnosis, military status, race, tumor histology, grade, FIGO surgical stage, adjuvant therapies, and disease-free survival. The chi(2) test was used for analysis of prognostic factors and adjuvant treatments between racial groups. Actuarial survival curves were calculated by using the method of Kaplan and Meier and compared by the log-rank test. Variables found to be significant on univariate analysis (P < 0.05) were entered into a multivariate Cox regression analysis. RESULTS Of 1811 patients meeting criteria for the study, racial distribution was 90% Caucasian, 4.4% African-American, and 5.5% Asian-Pacific Islander. African-Americans had more advanced stages of disease compared to Caucasians (P < 0.001). Both African-Americans and Asian-Pacific Islanders had higher grade tumors and less favorable histologic types than Caucasians (P < 0.05). The extent of adjuvant therapies was similar for racial groups. African-Americans and Asian-Pacific Islanders had significantly worse 5-year disease-free survivals than Caucasians (P = 0.007). Additional poor prognostic factors included age >60 years, grade, unfavorable histology, and stage. On multivariate analysis age >60 years, stage, and Asian-Pacific Islander race remained significant prognostic factors. CONCLUSION African-Americans and Asian-Pacific Islanders had worse survivals than Caucasians. After controlling for imbalances in clinicopathologic factors, Asian-Pacific Islander race was found to be a newly identified poor prognostic factor.

Comparative assessment of hypercoagulability in women with and without gynecologic malignancies using the thromboelastograph coagulation analyzer

The hypercoagulability status of women with and without gynecologic malignancies was compared using the thromboelastograph coagulation analyzer. Blood specimens from 25 women with newly diagnosed gynecologic malignancies and from 21 age-matched controls were analyzed. Hypercoagulability is defined by a short R value (min), a short K value (min), an elevated maximum amplitude (MA) value (mm), and a broad α-angle (°). A two-tailed, two-sample t-test was used for statistical analysis. When compared with specimens from age-matched controls, specimens from women with gynecologic malignancies demonstrated values consistent with hypercoagulability. The specific parameters are presented as a mean (± SD). Patients with gynecologic malignancies were found to have a short R value (7.1 ± 2.1 vs. 11.8 ± 1.8 min; P < 0.001), a short K value (3.1 ± 0.9 vs. 4.6 ± 0.9 min; P < 0.001), a prolonged MA value (64.7 ± 5.4 vs. 58.8 ± 6.1 mm; P = 0.001), and a greater α-angle (70.6 ± 5.3 vs. 61.6 ± 4.9°; P < 0.001). Detection of hypercoagulability as measured by thromboelastography is statistically more common among women with gynecologic malignancies compared with age-matched controls. Future studies may address the use of thromboelastography to identify patients at risk for gynecologic malignancies.

Elevated aromatase expression correlates with cervical carcinoma progression

OBJECTIVES We have previously demonstrated that aromatase mRNA is induced in cervical carcinomas compared to normal tissue, suggesting that in situ aromatase expression leading to elevated local estrogen production may contribute to cervical carcinogensis. Our objectives are to examine 1) whether aromatase protein and activity are induced in cervical carcinomas, 2) aromatase expression correlates with disease stage, and 3) inflammatory cytokines (e.g., IL-6 and TNFalpha) may correlate with aromatase expression. METHODS RNA and protein were isolated from human cervical carcinomas and normal cervical biopsies to examine aromatase expression, using real-time RT-PCR, Western blot analysis, and immunohistochemistry. Aromatase activity in tissue was measured using the tritiated water release method. IL-6 and TNFalpha expression was also examined. RESULTS Aromatase protein and activity levels were increased in cervical carcinomas compared to normal tissue. RNA levels correlated significantly with disease progression, with highest aromatase expression detected in stage IV tumors (p<0.001, R(2)=0.77). Aromatase promoters 1.3 and 1.4 were elevated in cervical carcinomas and in cervical cancer cells. The expression of inflammatory cytokines IL-6 and TNFalpha, known to induce aromatase, significantly correlated with aromatase expression (R(2)>0.9). TNFalpha treatment induced aromatase expression in cervical cancer cells. CONCLUSION Increased aromatase protein and activity in cervical carcinomas and the correlation of its expression with disease stage implicates it in cervical carcinogenesis. The correlation of IL-6 and TNFalpha expression with aromatase suggests that these inflammatory cytokines may induce aromatase expression, which is confirmed by induction of aromatase expression due to TNFalpha treatment of cervical cancer cells.

Clinical and Pathologic Features of Hispanic Endometrial Cancer Patients with Loss of Mismatch Repair Expression

Objectives Approximately 3% to 5% of endometrial cancers (EC) are associated with Lynch syndrome (LS). The clinical characteristics and prevalence of LS have not been well studied in the US Hispanic population. Hispanics are the largest and fastest growing ethnic minority group in the United States. We sought to characterize the demographics, tumor characteristics, and prevalence of loss of mismatch repair (MMR) protein expression in a large Hispanic population with EC. Methods From January 1, 2005, to August 1, 2012, 83 women of Hispanic ethnicity diagnosed with EC 50 years and younger were identified. Clinical and pathologic data were abstracted from the electronic medical record. Tumor studies included immunohistochemistry of MLH1, MSH2, MSH6, and PMS2 and methylation of the MLH1 promoter. Results Ninety-five percent of patients were overweight or obese. The mean body mass index was 40.1 kg/m2, 75% had irregular menses, 36% had diabetes, 46% were nulliparous, and 95% had endometrioid histology. Thirteen patients (15.7%) had tumor MMR deficiency due to a presumed germline mutation (9 MSH6, 3 MSH2, and 1 MLH1). The pattern of MMR protein loss was consistent with the expected binding properties of the MMR heterodimer complexes. No significant difference was found in clinical or pathological variables between patients with and without MMR deficient tumors. Conclusions The prevalence of molecular findings consistent with LS was at least as high as other populations of varied geography, race, and ethnicity. We found no reliable factors to include body mass index, family history, synchronous tumors, or pathologic tumor features to serve as triage markers for which ECs should be screened for MMR protein loss. Our findings support a recommendation for universal screening of ECs utilizing 2-antibody testing with MLH1 promoter methylation testing as indicated up to 60 years or older. Our recommendations should be generalizable to other Hispanic populations in the Southern United States.