1. In a cohort of 98 patients diagnosed with pancreatic adenocarcinoma who underwent surgical resection, high levels of hypoxia-inducible factor 1 alpha (HIF-1α) expression in tumor cells was significantly associated with distant disease recurrence.
Evidence Rating Level: 2 (Good)
Study Rundown: Pancreatic adenocarcinoma (PAC) is the fourth leading cause of cancer-related deaths in the United States. In patients with resectable PAC, distant recurrence is associated with a poor prognosis. However, there is currently no accurate method of predicting which patients will experience recurrence at the time of surgical resection. Hypoxia-Inducible Factor 1-alpha (HIF-1α) is an oxygen-sensitive transcription factor that serves as an adaptive switch for tumor cells to undergo angiogenesis and glycolytic metabolism. The purpose of this study was to determine whether HIF-1α may serve as a prognostic biomarker of distant recurrence in PCA. The authors analyzed HIF-1α expression in tumor tissue collected from 98 patients with early-stage PCA that underwent surgical resections and tracked patient outcomes for local or distant disease recurrence. After a median follow-up of 16 months, the authors demonstrated that high HIF-1α expression was significantly associated with distant disease recurrence. Furthermore, patients with low HIF-1α expression was associated with isolated local recurrence. Overall, approximately 50% of the patient cohort demonstrated high HIF-1α expression. The results of this study support the potential use of HIF-1α tumor expression as a predictive biomarker for distant recurrence in patients with early-stage PAC. The major limitation of this study is that the staining method of grading HIF-1α expression may be inadequate to capture tumor heterogeneity often observed in PAC. Furthermore, the follow-up time may not adequately capture all recurrence events in either the low or high HIF-1α groups. Additional prospective trials are required to accurately quantify this association.
Relevant Reading: Targeting HIF-1 for cancer therapy
In-Depth [prospective cohort]: In this study, tumor blocks were collected from 98 patients with early-stage PAC that underwent surgical resection. Patients were excluded if they had received neoadjuvant chemotherapy or radiation therapy. Immunohistochemistry (IHC) staining for HIF-1α was performed and expression was graded as high or low by two pathologist specializing in pancreatic cancer. The primary endpoint was local recurrence (disease in the pancreas, pancreatic bed, or associated lymph nodes) or distant recurrence (radiologic or pathologically confirmed recurrence in other sites). After a median follow-up of 16.3 months, 54% (n=53) of patients had high nuclear HIF-1α expression in tumor, with the remaining showing low expression. A total of 26.5% (n=26) of patients had distant recurrence, 8% (n=8) of patients had local recurrence, and 14% (n=13) had both local and distant recurrence. Multivariate analysis demonstrated that high HIF-1α expression was significantly associated with higher rates of distant recurrence (OR: 2.46; 95% CI: 1.059-5.719; p=0.036) but lower rates of local recurrence (OR: 0.106; 95% CI: 0.013-0.902; p=0.040).
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