In a single-institution study reported in JAMA Surgery, Shoucair et al found that matrix metalloproteinase 7 (MMP-7) expression in fine-needle aspiration biopsy specimens was associated with pathologic response to neoadjuvant therapy in patients undergoing resection for pancreatic ductal adenocarcinoma.
Study Details
The study involved a discovery cohort (n = 23) and validation cohort (n = 80) at Johns Hopkins Hospital. Targeted RNA sequencing of frozen fine-needle aspiration biopsy specimens from the discovery cohort was performed to identify genes with aberrant expression that may have been associated with pathologic response to neoadjuvant therapy.
Immunohistochemical staining was performed in fine-needle aspiration biopsy specimens in the validation cohort to assess expression of MMP-7 and its association with pathologic response. Pathologic response to neoadjuvant therapy was assessed using College of American Pathologists (CAP) scores, with favorable response indicated by a score of 0 (complete response) or 1 (marked response) and unfavorable response indicated by a score of 2 (partial response) or 3 (poor or no response).
Key Findings
In the discovery cohort, 80.0% of both CAP score 2 samples (4 of 5 samples) and CAP score 3 samples (12 of 15 samples) overexpressed MMP-7 with a fold-change > 1.5 compared with CAP score 1 samples (3 of 3 samples).
In the validation cohort, 34 patients were MMP-7–negative and 46 were MMP-7–positive. MMP-7–negative patients were significantly more likely to have a favorable pathologic response (odds ratio = 21.25, 95% confidence interval = 6.19–72.95, P = .001). All eight patients with a pathologic response score of 0 were negative for MMP-7.
In multivariable Cox proportional hazards regression modeling in the validation cohort, the addition of MMP-7 expression to a model consisting of chemoradiotherapy, baseline CA 19-9 level, baseline tumor size on imaging, and histologic grade of differentiation increased the receiver operating characteristic area under the curve (AUC) for prediction of favorable pathologic response from 0.726 to 0.906 (P < .001). The addition of MMP-7 expression to the same model plus stratification by resectability status also resulted in a significant improvement in AUC.
In the validation cohort, the positive and negative predictive values of MMP-7 expression for predicting unfavorable pathologic response were 88.2% and 73.9%, respectively.
The investigators concluded, “Assessment of MMP-7 expression on fine-needle aspiration biopsy specimens at the time of diagnosis may help identify patients who would benefit the most from neoadjuvant therapy.”
Jun Yu, MD, PhD, and Jin He, MD, PhD, of the Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Johns Hopkins University, are the corresponding authors for the JAMA Surgery article.
Disclosure: The study was supported by the Nikki Mitchell Foundation and Ben and Rose Cole Charitable Pria Foundation. For full disclosures of the study authors, visit jamanetwork.com.
