HMGA2 protein as a biomarker of dysplasia in IPMN

DiMaio_headshotChristopher J. DiMaio, MD, FASGE, from the Icahn School of Medicine at Mount Sinai, Mount Sinai Medical Center, in New York, New York, USA discusses his article “Pancreatic cyst fluid concentration of high-mobility group A2 protein acts as a differential biomarker of dysplasia in intraductal papillary mucinous neoplasm.”

No reliable cyst fluid biomarkers exist that allow for preoperative identification of patients with intraductal papillary mucinous neoplasms (IPMNs) and high-risk pathology. High-mobility group (HMG) A2 protein has been demonstrated to be a biomarker of dysplasia in IPMN. It is unknown whether HMGA2 protein is present in the cyst fluid from IPMNs. The aims of this study were to determine whether HMGA2 protein is present in the cyst fluid of IPMNs and demonstrate whether HMGA2 protein concentration correlates with degree of dysplasia. DiMaio_fig

Figure 3. Immunohistochemistry staining for high-mobility group A2 in pathology specimens: negative staining in benign mucinous cystic neoplasms (A), positive staining in intraductal papillary mucinous neoplasm with invasive cancer (B), and pancreatic adenocarcinoma (C).

Branch duct IPMN (BD-IPMN) are the most commonly encountered pancreatic cystic neoplasm. These lesions have the potential for malignant transformation. Given this risk, the identification of a BD-IPMN represents an important opportunity to identify patients at increased risk of the development of pancreatic cancer, and thus to intervene before the development of malignancy. However, current diagnostic modalities in the evaluation of suspected BD-IPMN fall short in their ability to risk stratify any particular patient. As such, a new pancreatic cyst fluid biomarker could have a role in identifying patients who would benefit most from surgical resection.

Cyst fluid samples were analyzed from 31 patients with pathologically proven and resected BD-IPMNs. HMGA2 protein was detected in 97% of the fluid samples. Median cyst fluid HMGA2 protein concentration (ng/mL) was as follows: LGD, 0.6 (interquartile range [IQR] 0.35-0.6); MD, 1.55 (IQR 0.65-2.7); HGD, 4.2 (IQR 1.7-9.2) (P < .05). The median HMGA2 protein concentration was significantly higher in the HGD group (4.2 ng/mL, IQR 1.7-9.2) compared with the concentration in the low-risk group (1.1 ng/mL, IQR 0.6-2.7, P =  .03).  These results support the hypothesis that HMGA2 can act as a differential biomarker of dysplasia in IPMN.

Future studies should focus on prospective collection of fluid by EUS-FNA in a larger sample size, and should be correlated with specific radiologic and endosonographic findings.

Read the article abstract here.

The information presented in Endoscopedia reflects the opinions of the authors and does not represent the position of the American Society for Gastrointestinal Endoscopy (ASGE). ASGE expressly disclaims any warranties or guarantees, expressed or implied, and is not liable for damages of any kind in connection with the material, information, or procedures set forth.

3 thoughts on “HMGA2 protein as a biomarker of dysplasia in IPMN

  1. Fauze Maluf-Filho

    Dear Dr. DiMaio,

    Congratulations on your nice publication.
    Did you perform a ROC curve to determine a possible cutoff value for the HMG2A value?
    Thank you

  2. Christopher DiMaio

    Thank you for your interest and comments. We performed an ROC curve, and the AUC was 0.74. We did not calculate possible “cutoff” values given the small sample size.

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