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1.
Am J Clin Pathol ; 157(1): 90-97, 2022 Jan 06.
Article in English | MEDLINE | ID: mdl-34463332

ABSTRACT

OBJECTIVES: To describe clinicopathologic characteristics and survival outcomes of endometrial adenocarcinomas stratified by mismatch repair (MMR) status. METHODS: Single-institution, retrospective study of all women with endometrioid adenocarcinomas treated from January 2012 through December 2017. Patients were categorized into one of three groups based on MMR testing: intact MMR expression (MMR+), probable MMR mutation (MMR-), or MLH1 hypermethylation (hMLH1+). Demographics, pathologic characteristics, recurrence rates, and survival differences were analyzed. RESULTS: In total, 316 women were included in the analysis: 235 (74.4%) patients in the MMR+ group, 10 (3.1%) in the MMR- group, and 71 (22.5%) in the hMLH1+ group. Patients with hMLH1+ were significantly older, exhibited higher-grade histology and presence of lymphovascular space invasion, and were more likely to have received adjuvant treatment. The early stage hMLH1+ patients were more likely to recur (15.3% hMLH1+ vs 2.3% MMR+ vs 12.5% MMR-, P < .001). Hypermethylation remained a significant predictor of recurrence in multivariable analysis (odds ratio, 5.09; 95% confidence interval [CI], 1.54-16.86; P = .008). Recurrence-free survival was significantly reduced in early stage hMLH1+ (hazard ratio, 7.40; 95% CI, 2.80-21.62; P < .001). CONCLUSIONS: Women with hMLH1+ endometrial cancer have worse prognostic features and recur more frequently, even in patients traditionally considered low risk for recurrence.


Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , Carcinoma, Endometrioid/diagnosis , Carcinoma, Endometrioid/genetics , DNA Methylation , DNA Mismatch Repair/genetics , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/genetics , Female , Humans , MutL Protein Homolog 1/genetics , Retrospective Studies
2.
Gynecol Oncol ; 150(2): 338-342, 2018 08.
Article in English | MEDLINE | ID: mdl-29935911

ABSTRACT

OBJECTIVE: To determine whether distance to a tertiary care facility affects outcomes for locally advanced cervical cancer and to evaluate the impact of receiving care at non-specialized centers in rural communities. METHODS: Retrospective, single institution study of patients with locally advanced cervical cancer managed with chemo-radiation from January 1, 2000 to June 1, 2014. Kaplan-Meier survival curves and Cox proportional hazard models were used to compare progression free and overall survival for patients by median distance to the tertiary care facility (<72 miles or >72 miles) and facility where treatment was received. RESULTS: 180 patients met inclusion criteria. There was no difference in PFS or OS between the travel distance cohorts. When compared by location of external beam radiation, patients treated at outside facilities were older (p = 0.02) and significantly more likely to be insured (95.6% versus 71.7%, p < 0.0002). There were more recurrences among patients treated at outside facilities (31.1% versus 15.8%) but this was non-significant (p = 0.24). On multivariable analysis, FIGO stage and insurance status were associated with overall survival. Uninsured patients had a significantly increased hazard risk of death as compared to privately insured patients (HR 3.85 95% CI 3.07-4.64, p = 0.0008). CONCLUSIONS: Median distance to a tertiary care facility had no significant impact on PFS or OS, however treating facility for radiation may influence recurrence rates. Having non-private insurance or being uninsured is significantly associated with increased risk of death and speaks to the many barriers these patients face.


Subject(s)
Health Services Accessibility/statistics & numerical data , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/therapy , Academic Medical Centers , Adult , Chemoradiotherapy , Cohort Studies , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Staging , Retrospective Studies , Rural Population/statistics & numerical data , Survival Rate , Uterine Cervical Neoplasms/pathology , Virginia/epidemiology
3.
Cancer ; 123(6): 977-984, 2017 05 15.
Article in English | MEDLINE | ID: mdl-28263384

ABSTRACT

BACKGROUND: Mesothelium vascular cell adhesion molecule-1 (VCAM-1) expression in the metastatic epithelial ovarian cancer (EOC) microenvironment is induced by tumor and mediates tumor cell invasion. VCAM-1 imaging suggests expression during treatment is an indicator of platinum resistance. Here, we assess the potential prognostic significance of mesothelium VCAM-1 expression and prospectively evaluate whether soluble VCAM-1 (sVCAM-1) is a surrogate for mesothelium expression. METHODS: A retrospective review of EOC patients was performed to evaluate outcomes with mesothelium VCAM-1 expression determined by immunohistochemistry of peritoneum or omentum specimens. A prospective cohort of EOC patients was identified and followed through primary treatment. Serum for sVCAM-1 evaluation, which was performed via enzyme-linked immunosorbent assay, was collected before surgery or neoadjuvant chemotherapy and at each treatment cycle. Peritoneal specimens were obtained during debulking to assess mesothelial VCAM-1 expression. RESULTS: A retrospective review identified 54 advanced-stage EOC patients. Patients expressing mesothelium VCAM-1 had shortened overall survival (44 vs 79 months, P = 0.035) and progression-free survival (18 vs 67 months, P = 0.010); the median time to platinum resistance was 36 months for VCAM-1-expressing patients and not yet determined for the VCAM-1-negative group. In our prospective observational cohort, 18 EOC patients completed primary treatment; 3 were negative for mesothelium VCAM-1 expression, and sVCAM-1 did not vary between groups. CONCLUSIONS: Mesothelium VCAM-1 expression is negatively associated with progression-free and overall survival in EOC. This is especially compelling in light of previous data suggesting that persistent VCAM-1 expression during treatment is an indicator of platinum resistance. Our pilot study had insufficient cases to determine whether sVCAM-1 would substitute for mesothelium expression. Cancer 2017;123:977-84. © 2016 American Cancer Society.


Subject(s)
Epithelium/metabolism , Gene Expression , Neoplasms, Glandular and Epithelial/genetics , Neoplasms, Glandular and Epithelial/mortality , Ovarian Neoplasms/genetics , Ovarian Neoplasms/mortality , Vascular Cell Adhesion Molecule-1/genetics , Adult , Aged , Biomarkers, Tumor , Carcinoma, Ovarian Epithelial , Combined Modality Therapy , Epithelium/pathology , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Grading , Neoplasm Staging , Neoplasms, Glandular and Epithelial/diagnosis , Neoplasms, Glandular and Epithelial/therapy , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/therapy , Prognosis , Retrospective Studies , Treatment Outcome , Vascular Cell Adhesion Molecule-1/blood
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