Serpin Peptidase Inhibitor Clade A Member 1 as a Potential Marker for Malignancy in Insulinomas

Abstract

Purpose: The biological behavior of insulinomas cannot be predicted based on histopathologic criteria in which the diagnosis of malignancy is confirmed by the presence of metastases. In this study, microarray and quantitative real-time reverse transcription-PCR were applied to identify differentially expressed genes between malignant and nonmalignant insulinomas to search for useful biomarkers to recognize the metastatic potential of insulinomas. Experimental Design: CodeLink human bioarrays were used to analyze differences in f20,000 genes between six well-differentiated endocrine tumors of benign behavior compared with one well-differentiated endocrine carcinoma (WDEC) and three metastases of endocrine carcinomas (MEC). Quantitative real-time reverse transcription-PCR was used to validate differential expressions of five genes in a series of 35 sporadic insulinomas. Serpin peptidase inhibitor clade A member 1 (SERPINA1; a-1-antitrypsin) expression, identified as up-regulated in malignant insulinomas, was also evaluated by immunohistochemistry. Results: Analysis of microarray data resulted in 230 differentially expressed genes. Gene Ontology analysis identified serine-type endopeptidase activity and serine-type endopeptidase inhibitor activity as pathways presenting significant differential expression. Protease serine 2 and complement factor B (from serine-type endopeptidase activity pathway) were respectively confirmed as up-regulated in well-differentiated endocrine tumors of benign behavior (WDET) and inWDEC/MEC. Angiotensinogen and SERPINA1 (from serine-type endopeptidase inhibitor activity pathway) were confirmed as up-regulated inWDEC/MEC. SERPINA1was shown to be expressed in 85.7% of malignant versus14.3% of nonmalignant insulinomas by immunohistochemistry. Conclusions: Our data are consistent to the possibility that SERPINA1is a marker of malignancy in insulinomas. Given the widespread availability of antibody anti-a-1-antitrypsin in pathology services, SERPINA1expression evaluation might be of clinical utility in recognizing patients more likely to develop an aggressive presentation.

Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma

“…[1][2][3][4] At present, only a few specific biomarkers for cutaneous SCC have been identified, including STAT3, 44 E-cadherin, 45 and matrix metalloproteinases 13, 46 12, 47 and 7. 6,48 SerpinA1 has been previously suggested as a biomarker for the progression of insulinoma 49 and thyroid cancer. 50 In this study, we introduced SerpinA1 as a potential biomarker for the progression of cutaneous SCCs combined with other biomarkers mentioned previously herein.…”

Molecular imaging in the investigation of hypoglycaemic syndromes and their management

“…This supports our experience with metastatic insulinoma with the vast majority of cases having high uptake on 68 Ga DOTATATE PET/CT. Further evidence of an association between SSTR expression and malignancy in insulinomas was identified in a quantitative PCR analysis of SSTR5 expression in a series of 16 primary insulinomas (four of which were plurihormonal) and two insulinoma metastases (de Sa et al 2006). Interestingly, SSTR5 mRNA was positively correlated with histological features of tumour aggressiveness, including large tumour diameter, proportion of cells with nuclear atypia, and plurihormonal secretion.…”

Somatostatin Receptors 3, 4 and 5 Play Important Roles in Gallbladder Cancer

“…SSTR2 and SSTR3 induce cell apoptosis and SSTR1 and SSTR5 are related with cell cycle and affect cell proliferation and differentiation (Lamberts et al, 2002). Research has shown that SSTR5 is concerned strongly with infiltration of tumor and the expression of SSTR5 in insulinoma is lower markedly than normal tissue, indicating that SSTR5 has an intimately relationship with the proliferation of tumor (de Sa et al, 2006). Thus, therapeutic drugs effects depend on the expression of SSTRs in gallbladder cancer tissue.…”