Abstract
PurposeHMGA2 has frequently been found in benign as well as malignant tumors and a significant association between HMGA2 overexpression and poor survival in different malignancies was described. In pancreatic ductal adenocarcinoma (PDAC), nuclear HMGA2 expression is associated with tumor dedifferentiation and presence of lymph node metastasis. Nevertheless, the impact of HMGA2 occurrence in other cell compartments is unknown.MethodsIntracellular distribution of HMGA2 was analyzed in PDAC (n = 106) and peritumoral, non-malignant ducts (n = 28) by immunohistochemistry. Findings were correlated with clinico-pathological data. Additionally, intracellular HMGA2 presence was studied by Western blotting of cytoplasmic and nuclear fractions of cultured cells.ResultsHMGA2 was found in the cytoplasm and in the nucleus of cultured cells. In human tumor tissue, HMGA2 was also frequently found in the cytoplasm and the nucleus of tumor cells, however, nuclear staining was generally stronger. Direct comparison from tumor tissue with corresponding non-neoplastic peritumoral tissue revealed significantly stronger expression in tumors (p = 0.003). Of note, the nuclear staining was significantly stronger in lymph node metastatic cell nuclei compared to primary tumor cell nuclei (p = 0.049). Interestingly, cytoplasmic staining positively correlated with lymph vessel (p = 0.004) and venous invasion (p = 0.046).ConclusionHMGA2 is a prognostic marker in PDAC. Firstly, we found a positive correlation for cytoplasmic HMGA2 expression with lympho-vascular invasion and, secondly, we found a significantly stronger nuclear expression of HMGA2 in cancer-positive lymph node nuclei compared to primary tumor cell nuclei. So far, the role of cytoplasmic HMGA2 is nearly unknown, however, our data lend support to the hypothesis that cytoplasmic HMGA2 expression is involved in nodal spread.
Highlights
Effective treatment of patients with pancreatic ductal adenocarcinoma (PDAC) requires early diagnosis and intervention
HMGA2 is localized to the cytosol and nucleus in different tumor cell lines
We aimed to investigate whether the expression of HMGA2 and, in particular, the pattern of its intracellular distribution correlates with histopathological parameters and correlates with patient prognosis
Summary
Effective treatment of patients with pancreatic ductal adenocarcinoma (PDAC) requires early diagnosis and intervention. The high mobility group A2 (HMGA2/HMGI-C) is an architectural transcription factor and belongs to the high mobility group AT-hook (HMGA) gene family. It is highly expressed in embryonic tissue, whereas its expression drops during the differentiation being hardly detectable in healthy adult tissue (Chiappetta et al 1996; Huang et al 2018). Not all tumors with elevated HMGA2 expression show significant association with survival rates (e.g., ovarian cancer Huang et al 2018; Nie et al 2018) or esophageal cancer (Huang et al 2018). HMGA2 represents a reliable marker of prognostic value in some, but not all cancers
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