RESUMEN
BACKGROUND: Our aim was to characterize the clinicopathological features and outcomes of gastrointestinal stromal tumors (GISTs) arising from the esophagus and gastroesophageal junction (GEJ) and describe the survival of patients treated at our institution as well as from a national hospital-based registry. METHODS: Twenty-eight cases were identified using the Mayo Clinic Cancer Registry from 1997 to 2016, and 1,010 cases from the National Cancer Database (NCDB) between 2004 and 2014, with analysis of TNM staging, histopathological features, mitotic index, immunohistochemical studies, and KIT mutational analysis. RESULTS: At Mayo Clinic, the tumors ranged in size from 0.3-13 cm (mean 5.40 cm). IHC results were: CD117 (KIT) in 100% (23/23 cases) and DOG1 in 100% (6/6), followed by CD34 (85.7%, 12/14), smooth muscle actin (27.8%, 5/18), desmin (18.2%, 2/11), and S-100 protein (13.3%, 2/15). Mutational analysis (performed in 10 cases) showed KIT exon 11 mutations in 8 cases; KIT mutation was not identified in 2 cases (presumed wild-type). Two-thirds of patients underwent surgery, of which 70% had an esophagectomy. Fourteen patients received adjuvant imatinib mesylate. Five patients had liver metastases at the time of diagnosis; none had lymph node metastases. A total of 38.9% of cases had recurrent or metastatic disease. Complete clinical follow-up was available for 10 patients (median follow-up duration 31.5 months; range, 10-145 months): one (male) had a local recurrence at the anastomotic site and one (female) suffered a liver metastasis; the others were either disease-free or had stable disease at the time of last follow-up. There was a significant association seen among metastatic disease and mitotic count >5/50 high-powered field (HPF) (P=0.016), with median mitotic rate 90/50 HPF (range, 7-500) for metastatic tumors versus 6/50 HPF (range, 0-100) for non-metastatic tumors. For metastatic disease, median tumor size was 7.3 cm (range, 1-66 cm) compared to 4.8 cm (range, 0.02-71 cm) for non-metastatic disease, which was also statistically significant (P≤0.0001). Two hundred and fifty-eight NCDB cases were risk stratified using the Joensuu criteria. Among 89 low risk category tumors, only 2 (2.2%) were ultimately metastatic. A total of 10.9% (15/138) of high risk category tumors were metastatic. The median overall survival (OS) from the time of diagnosis for the Mayo Clinic cohort was 129.5 months (95% CI, 55.7-not reached), with 5-year OS 85.7%. Median OS for the NCDB cohort was 135.95 months (95% CI, 104.08-not reached) with 5-year OS 68.2%. Superior OS was seen in females (HR 0.67, 95% CI, 0.49-0.89, P=0.006). CONCLUSIONS: Among esophageal and GEJ GISTs, metastatic disease was associated with increased mitotic count and increased tumor size. Men were found to have inferior OS. The Joensuu risk criteria were validated for risk stratification of esophageal and GEJ GISTs.
RESUMEN
BACKGROUND: Although the lack of CDX2 expression has recently been proposed as a potential biomarker for a high risk of relapse in patients with stage II and III colon cancer after complete surgical resection, its prognostic role in metastatic colorectal cancer (CRC) remains unclear and warrants investigation. MATERIALS AND METHODS: We identified 145 patients treated at our institution from 2006 to 2016, including 66 patients with CDX2-negative metastatic CRC and a comparison cohort of 79 patients with CDX2-positive metastatic CRC. Overall survival (OS) and progression-free survival (PFS) for first-line systemic therapy were estimated using the Kaplan-Meier method. The associations of CDX2 expression with survival were evaluated using Cox proportional hazards regression models. RESULTS: The prevalence of absent CDX2 expression in our cohort was 5.6%. Patients with CDX2-negative metastatic CRC were significantly more likely to be female, and to have right-sided primary tumors, poorly differentiated histologic features, and distant lymph node metastasis. The median OS for patients with CDX2-negative and -positive metastatic CRC was 8 and 39 months, respectively (hazard ratio [HR], 4.04; 95% confidence interval [CI], 2.49-6.54; P < .0001). After adjusting for covariates in a multivariate model, the association of a lack of CDX2 expression and OS remained statistically significant (HR, 4.52; 95% CI, 2.50-8.17; P < .0001). In addition, the median PFS (3 vs. 10 months; HR, 2.23; 95% CI, 1.52-3.27; P < .0001) for first-line chemotherapy was significantly decreased in patients with CDX2-negative metastatic CRC. CONCLUSION: The results of the present study show that a lack of CDX2 expression in metastatic CRC is an adverse prognostic feature and a potential negative predictor of the response to chemotherapy.