Pathologic, immunologic, and clinical analysis of the microsatellite instability phenotype in endometrial carcinoma.

The objective of this study was to determine if quantifying the microsatellite instability (MSI) phenotype could serve as a biomarker for clinical and immunologic features of deficient mismatch repair (dMMR) endometrial cancer (EC). Patients with EC undergoing hysterectomy whose tumors demonstrated dMMR were included. Immunohistochemistry (IHC) of mismatch repair proteins and polymerase chain reaction analysis of NR27, BAT25, BAT26, NR24, and NR21 microsatellite loci were performed on each case. The MSI phenotype was quantified by subtracting the number of nucleotides of each microsatellite in tumor tissue from the corresponding microsatellite in paired normal tissue and summing the absolute differences. This was termed marker sum (MS) and is a novel quantification. Tumor-infiltrating lymphocytes (TILs) were identified by IHC for CD3, CD4, and CD8 and quantified with digital image analysis. Tumor infiltration of lymphocytes and clinical characteristics were stratified by MS. Four hundred fifty-nine consecutive patients with dMMR EC were analyzed. MS ranged from 1 to 32. Post hoc, 2 cohorts were defined using receiver operating characteristic curves (MS less than 13 and MS greater than 12). With the exception of tumor grade, all clinical and pathologic features, all tumor characteristics, and the numbers of TILs were similar between cohorts. The MSI phenotype is highly variable in dMMR EC, and no correlation between the immune profile and the severity of the MSI phenotype was observed.

A case series of triplet anti-hormonal therapy in androgen receptor-positive recurrent adult ovarian granulosa cell tumor.

Therapeutic options for recurrent adult granulosa cell tumors (AGCT) are limited. After examining the hormonal pathways involved in FOXL2-mutated granulosa cell tumor development, a novel treatment regimen was utilized for recurrent AGCT: a combination of an androgen receptor antagonist, a gonadotropin-releasing hormone receptor agonist, and an aromatase inhibitor for hormonal blockade. In this case series, seven patients at our institution were treated with bicalutamide 50 mg orally once daily, Leuprolide acetate 7.5 mg intramuscular (IM) injection every 4 weeks, and a daily oral aromatase inhibitor. These patients had recurrent AGCT with androgen receptor positive tumors and had failed prior aromatase inhibitor therapy. All patients had undergone multiple surgical resections and many cycles of chemotherapy. Patients were monitored for toxicities and for response to treatment. Of the seven patients receiving the triple therapy, six saw clinical benefit. Two patients demonstrated a partial response and four patients had stable disease. One patient had progressive disease on the regimen. For the two patients who had a partial response to the triple therapy, there was strong expression of the androgen receptor (AR) noted on tumor immunohistochemistry. This drug combination was well-tolerated except for severe hot flashes in one patient. In conclusion, the triple therapy combination of an androgen receptor antagonist, aromatase inhibitor, and GnRH agonist demonstrated measurable responses in patients with recurrent AGCTs after multiple previous treatments. A prospective clinical trial is planned to further investigate these findings.

Postoperative Risks for Hispanic Patients Undergoing Hysterectomy for Benign Indications.

BACKGROUND: Hispanic patients have previously been shown to have relatively lower odds of complication following hysterectomy compared with non-Hispanic white patients, but little is known about specific risks for this group. Our primary objective was to identify differences in proportions of specific complications experienced by Hispanic patients following hysterectomy for benign indications as compared with non-Hispanic white patients. DESIGN: Retrospective cohort study examining differences in complication rates following benign hysterectomy between Hispanic and non-Hispanic white patients in NSQIP-participating hospitals from 2012 to 2016. MEASUREMENTS AND MAIN RESULTS: A total of 102,051 women were included. A total of 15.0% were Hispanic and 85.0% were non-Hispanic white. Hispanic patients were more likely to have class 1 or 2 obesity (59.7 vs 49.8%), diabetes (10.9 vs 6.7%), and anemia (hematocrit < 33: 14.1 vs 6.5%); p < 0.01 for all. Hispanic patients were more likely to undergo abdominal hysterectomy (30.0 vs 19.1%, p < 0.01) and to remain inpatient for 2-6 days (38.8 vs 24.0%, p < 0.01). After adjustment for possible confounders including anemia, an increased odds of requiring blood transfusion persisted only in the laparoscopic and vaginal groups. Hispanic patients had a decreased or equal odds for all other examined complications. CONCLUSIONS: Compared with non-Hispanic white patients, Hispanic women had a higher odds of requiring blood transfusion even when undergoing minimally invasive laparoscopic and vaginal approaches to hysterectomy. Despite a higher proportion of open surgery, Hispanic patients had a decreased or equal odds of postoperative complications.