Browsing by Author "Method, Michael W."

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    Effects of Slide Storage on Detection of Molecular Markers by IHC and FISH in Endometrial Cancer Tissues From a Clinical Trial: An NRG Oncology/GOG Pilot Study
    (Wolters Kluwer, 2022) Grushko, Tatyana A.; Filiaci, Virginia L.; Montag, Anthony G.; Apushkin, Marsha; Gomez, Maria J.; Monovich, Laura; Ramirez, Nilsa C.; Schwab, Carlton; Kesterson, Joshua P.; Seward, Shelly M.; Method, Michael W.; Olopade, Olufunmilayo I.; Fleming, Gini F.; Birrer, Michael J.; Medicine, School of Medicine
    We performed a pilot study in anticipation of using long-aged precut formalin fixed paraffin embedded (FFPE) tissue sections stored in real-world conditions for translational biomarker studies of TOP2A, Ki67, and HER2 in endometrial cancer. FFPE tissue blocks or unstained slides or both from GOG-0177 were collected centrally (1999-2000) and stored at room temperature. During 2004-2011 specimens were stored at 4°C. Matched pairs of stored slides and freshly cut slides from stored blocks were analyzed for TOP2A (KiS1), Ki67 (MIB1) and HER2 (Herceptest™) proteins. To assess DNA stability (HER2 PathVision), FISH was repeated on stored slides from 21 cases previously shown to be HER2-amplified. IHC staining intensity and extent, mean FISH copies/cell, and copy number ratios were compared using the kappa statistic for concordance or signed rank test for differences in old cut versus new cut slides. IHC results reflected some protein degradation in stored slides. The proportion of cells with TOP2A staining was lower on average by 12% in older sections (p=.03). The proportion of Ki67 positive cells was lower in stored slides by an average of 10% (p<.01). Too few cases in the IHC cohort were FISH positive for any conclusions. HER2 amplification by FISH was unaffected by slide storage. We conclude that use of aged stored slides for proliferation markers TOP2A and Ki67 is feasible but may modestly underestimate true values in endometrial cancer. Pilot studies for particular storage conditions/durations/antigens to be used in translational studies are warranted.
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    Utilization Patterns of Lymph Node Dissection in Endometrial Cancer Patients Without Distant Metastasis in the United States
    (2021-06) Alyea, Jennifer Marie; Dixon, Brian E.; Song, Yiqing; Zhang, Jianjun; Hess, Lisa M.; Method, Michael W.
    Endometrial cancer is the most common gynecologic cancer in the United States, and patients with early-stage endometrioid adenocarcinoma have a favorable prognosis. Over the past decade, the gynecologic oncology community has debated whether potential harms of systematic lymph node dissection (LND) outweigh potential benefits for these patients. To minimize number of nodes removed, sentinel lymph node dissection (SLND) is under investigation as an alternative. However, ongoing uncertainty of LND/SLND best practices may result in variations in disease management and discrepant outcomes. Methods Three retrospective cohort studies examined LND/SLND use in patients with endometrioid adenocarcinoma. Two examined temporal and geographic variations, respectively, utilizing the Surveillance, Epidemiology, and End Results (SEER) 18 dataset for the years 2004 through 2015. The third used the SEER-Medicare dataset from 2003 through 2016 to quantify and compare the risk of developing 6-month post-surgical lymphedema, lymphocele, hemorrhage, ileus, infection, thrombosis, and all-cause death by number of lymph nodes removed (0, 1-4, 5-9, or 10+). Results Time trend analyses found LND increased from 2004 through 2008, followed by a significant decline through 2015. SLND was rare and did not increase significantly. Significant geographic variation existed for LND use but not SLND. Per 1,000 patients, analyses of 6-month post-surgical complications found 6.5 experienced lymphedema, 3.9 experienced lymphocele, 15.7 experienced hemorrhage, 28.7 experienced ileus, 37.1 experienced infection, 18.6 experienced thrombosis, and 19.8 died. Controlling for size of primary tumor, tumor grade, comorbidities, race/ethnicity, age at diagnosis, adjuvant chemotherapy, and radiotherapy, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) showed greater risk for ileus (HR: 1.53; 95% CI: 1.24-1.90), infection (HR: 1.52; 95% CI: 1.25-1.83), and thrombosis (HR: 1.41; 95% CI: 1.09-1.82) when comparing removal of 10+ nodes versus 0 nodes. Conclusion Overall, these studies found significant temporal and geographic variation in LND, as well as increasing risk of post-surgical complications associated with increasing numbers of lymph nodes removed. Should continued research into SLND find strong evidence that it effectively detects cancer spread, patients may benefit through decreased risk of post-surgical ileus, infection, and thrombosis.